This study evaluates the psychological impact (PI) of the COVID-19 pandemic in frontline workers in Spain. Participants were 546 workers . They all completed online questionnaires assessing PI, sadness, concerns related to the COVID-19 pandemic, and demographic and work-related variables. All groups but protective services workers showed higher PI levels than the general population. Healthcare and grocery workers were the most affected, with 73.6% and 65.2% of the participants, respectively, showing a severe PI. Women showed a higher PI level. Healthcare workers in the regions with higher COVID-19 incidences reported greater PI levels. The main concerns were being infected by COVID-19 or infecting others. Levels of concern correlated with higher PI levels. The protection equipment was generally reported as insufficient, which correlated with higher PI levels. Professionals reporting to overwork during the crisis  showed higher PI levels. In the healthcare group, taking care of patients with COVID-19 (77%) or of dying patients with COVID-19 (43.9%) was associated with higher PI levels. The perceived social recognition of their work was inversely related to PI. Most of the sample had not received psychological support. We suggest some organizational measures for frontline institutions, such as the periodical monitoring or inclusion of psychologists specialized in crisis-management to prevent negative symptoms and provide timely support. Spain was a front door country during the first weeks of the COVID-19 pandemic spread in Europe. As of 17 September 2020, more than 600,000 infected cases and more than 30,000 deaths . DuringAs for grocery workers, food purchasing patterns have changed dramatically during the pandemic, turning from regular visits to shop both perishable and non-perishable products to sporadic hoarding behaviors such as non-perishable stockpiling or panic buying . Thus, “Regarding protective service workers such as police, militaries, and public safety workers, they frequently face an enormous diversity of physical and psychological hazards  that mayFinally, media professionals rarely appear as frontline workers in the literature except when in conflicts and war periods . In thoHence, once all the peculiarities of working during the COVID-19 pandemics in each frontline group of workers are stated, we present a study in which we aimed to explore their psychological symptomatic response to working during the COVID-19 pandemic and the potential demographic and work-related factors that may be associated with their symptoms. Additionally, such psychological symptomatic responses were compared across the four groups and with the data obtained from the Spanish general population in the study by Rodríguez-Rey et al. . By presN = 269), 19.2% were media professionals (N = 105), 16.3% were grocery workers (N = 89), and 15.2% were protective service workers (N = 83). All the participants were currently working or had worked at any time during the first wave of the COVID-19 sanitary crisis in Spain (March–May 2020). Thus, professionals who had not worked during the crisis were excluded from the study. Each subsample’s sociodemographic data are included in A total of 546 frontline professionals completed the study. Of those, 49.3% were healthcare workers , the average number of hours they had worked the week before, whether they had to overwork during the pandemic , the number of days since their last day off, the degree to which they perceived that they were working as a team during the crisis, and the availability of personal protection equipment in their workplace (those who telework did not have to answer such question). Healthcare workers were also asked to specify their position , their current work situation , the unit where they usually worked , the unit where they were working during the COVID-19 crisis, and their proximity to COVID-19 patients . Media professionals were asked about their working role , how much time they spent in direct contact with other people at work, the media they were working for during the crisis , their media’s audience impact , and whether they were teleworking or working on site. Grocery workers were asked about their working role , how much time they spent in direct contact with other people at work during the pandemic and the size of the store . Finally, protective security workers were asked about the force unit they belonged to  and their working role during the crisis .Impact of Event Scale-Revised IES-R; ,43). The. The43])Screening of depression: We asked the participants two questions: (1) Are you depressed? , which has proven to be an adequate screening question to detect depression with a sensitivity of 88% when the answers “Yes” and “I don’t know” are combined , and (2)Degree of concern: Participants were asked about the degree to which they were concerned  about different aspects in relation to their work during the COVID-19 pandemic. Some questions were common for all the groups, while some others were specific for each profession. The full list of assessed concerns is included in the concerns subsection within the results.Perceived social recognition and self-assessment of the importance of their work during the pandemic: Participants were asked whether they felt their work was recognized and whether they thought that their labor contribution was important during the pandemic .Support received by their company/workplace during the COVID-19 crisis: Participants were asked whether they were receiving any specific support to face the current crisis, and, if so, which support .Perceived severity of the COVID-19 crisis: Respondents indicated the perceived severity degree of the current crisis through a Likert scale ranging from 0 to 10.The study was approved by the Ethics Committee of the first and the third authors’ university. The data were collected online through a Google Forms questionnaire specific to each professional group. The four groups included on the study were selected based on the previous crisis-related literature and the international consideration of essential workers, as described in the introduction. The data collection period was between 21 March 2020  and 4 June 2020 . To recruit the sample, we distributed the questionnaires by email and social networks  following a snowball approach. Additionally, we contacted different professional networks and companies and asked them to spread the questionnaires. Specifically, for the healthcare workers group, we contacted the College of Physicians, several public tertiary hospitals located in different Spanish provinces , and the Alliance of private Spanish healthcare. For the media professionals, we contacted the Spanish Society for Scientific Communication, journals or agencies specialized in science (such as SINC and EFE), the Madrid Press Association , university press offices and individual journalists or media workers of Spanish public television (RTVE) or private channels , radios , and journals  covering different political orientations. For protective service workers, we contacted the Secretary of State, the National Union of Heads and Directors of Local Police, some Twitter accounts managed by local protective service units, high commands  in military units involved in COVID-19 tasks  who distributed the study information among their subalterns, and individual workers in the national and local police  and regional civil guards. Finally, for grocery workers, we did a search of supermarkets on a national scale, and then we distributed the study information among restaurant owners who had trade agreements with regional markets and sent emails asking the respective human resources departments to spread the questionnaires. All respondents provided informed consent prior accessing the questionnaires.Descriptive statistics were computed for the sociodemographic characteristics of the sample and the study variables consisting of frequencies and percentages for categorical variables and means and standard deviations (SDs) for scale variables. For the IES-R, standardized factorial scores were obtained based on the measurement model of the scale. The Q–Q plots were visually inspected, and skewness and kurtosis values were obtained; all of them indicated normality.t-tests. We also used t-tests to look for differences in the means of symptoms when the independent variable was dichotomic , adjusting the test result for non-homogeneous variances if the Levene’s test was significant. For multiple-category variables , we used a one-way ANOVA and looked at post-hoc Tukey (for homogeneous variances) or Games–Howell (for non-homogeneous variances) tests in case of a significant F-value. We obtained appropriate effect size statistics that adjusted for differences in group sizes—Hedges’ g for t-tests and η2 for ANOVAs. Bivariate associations between psychological impact and continuous variables  were assessed via Pearson’s correlation coefficient r. We used the Spearman’s correlation coefficient ρ to test bivariate associations between psychological impact and ordinal variables . All the tests were two-tailed, with a significance level of p < 0.05. The statistical analyses were performed using IBM SPSS Statistics for Windows, version 25 .Then, differences in the IES-R mean scores between each group and the general population  were exM = 44.85, t = 18.84, and p < 0.001), grocery workers , and media professionals  showed significantly higher psychological impacts than the general population (M = 27.95), while protective service workers showed similar levels .There were significant differences in the levels of sadness (range 0–10) between groups. Healthcare workers exhibited the highest scores, followed by grocery workers, media professionals, and, finally, protective service workers. Regarding the question “Are you depressed?” 49.8% of the participants in the healthcare workers group and 56.2% in the grocery workers group answered maybe or yes, while this percentage was 37.1% for media professionals and 18.1% for protective service workers.Mwomen = 0.41, SD = 0.75, Mmen = −0.82, SD = 1.02, t = −3.99, and p < 0.001) and in the grocery worker group . No gender differences were found in media professionals (t = −1.87 and p = 0.06) or protective service workers (t = −0.64 and p = 0.52). Age showed no correlation with psychological impact except for media professionals, where younger workers had higher IES-R scores (Pearson’s r = −0.28 and p < 0.001). Marital status was not associated with IES-R scores . Educational level was inversely related to the IES-R scores in healthcare workers (Spearman’s ρ = −0.13 and p = 0.03) and grocery workers (Spearman’s ρ = −0.23 and p = 0.03), while it was unrelated in media professionals and protective service workers. The number of children was directly and weakly correlated with psychological impact only in healthcare workers (Spearman’s ρ = 0.153 and p = 0.012).Women showed significantly higher psychological impacts than men both in the healthcare worker group (n = 296) and least affected (n = 250). We only found differences in the healthcare workers group, where those professionals in the most affected regions showed higher psychological impacts  than those living in the less affected areas . To analyze whether there were any differences in psychological impact, depending on the moment on which the participants completed the questionnaires, we divided the sample into three groups—those who participated during March (n = 294), those who participated during April (n = 140), and those who participated during May–June (n = 112). Differences were then tested with ANOVAs for each group of professionals. While there seemed to be an upward trend as time passed by in healthcare providers, protective service workers, and media professionals, the opposite tendency was found in the case of grocery workers. However, none of these differences were revealed to be significant (p > 0.05). It was close to significance in the case of grocery workers (F = 3.20 and p = 0.05), who showed lower psychological impacts in May–June (M = 36.88 and SD = 19.60) than in March (M = 47.82 and SD = 18.77) and April (M = 45.72 and SD = 16.15), but the post-hoc Tuckey test revealed no significant differences.The regions that were affected the most by COVID-19 in Spain during the data collection period were Comunidad de Madrid, Castilla La Mancha, and Cataluña . TherefoThe three main concerns for all the professional groups were about the contagion and the uncertainty about the crisis: the possibility of infecting a beloved one with COVID-19, becoming infected by COVID-19, and not knowing when this crisis was going to come to an end see . AssociaThe descriptive data of the common work-related variables and their associations with psychological impact can be found in The descriptive data of the work-related variables specific to each subsample and their association with psychological impact are included in As p = 0.03 for both; see All the groups perceived the crisis as very severe , but there were differences among groups of profession: grocery workers showed a higher perceived severity than media professionals and protective service workers  of working during the COVID-19 pandemic in four groups of frontline workers: healthcare, grocery, mass media, and protective professionals. Our main finding is that all four groups evaluated the pandemic situation as severe or very severe, reported feeling sadness, and showed mild to severe psychological impact, with health care and grocery professionals being, by far, the most affected groups and protective professionals being the least negatively affected. The course of this impact, although not significant, seemed to gradually increase as the pandemics progressed, except for the grocery workers, who showed a reverse pattern. It is also worth noting that, despite this general distress, most of the sample reported not having received psychological support.As a previous study evaluated the psychological impact of the Spanish general population with the same instrument (IES-R) at the beginning of the lockdown , we can The demographic and work-related variables that correlated with higher psychological impacts were lower educational level, female gender, considering the crisis as very severe, a lack of sufficient individual protection equipment, being afraid of infecting or becoming infected with COVID-19, uncertainty about the future, and subjective feelings within the work environment such as overworking, a low recognition of the work done, and not being emotionally prepared to cope with such a working scenario. Interestingly, previous working experience in critical situations did not appear to be a protective factor against psychological impact, which contradicts results from previous studies ,22.Some of the variables mentioned above may have accounted for the high psychological impact found in healthcare and grocery professionals. First, grocery workers had a lower educational level than the other groups and recognized not having the training needed to face this crisis, which may have increased their uncertainty and distress to face such a new shift . Other CM = 11.64). The perception of overworking was associated with higher psychological impact in all frontline workers’ mental health, except for protective service workers. However, the number of extra hours did not correlate with higher psychological impacts. This result shows that it is not the objective number of extra hours worked but the subjective feeling of overworking that influences mental health. For example, some media professionals could be used to stay permanently updated, but during the coverage of the pandemic, the flow of information was constant, varying, and with such potential amount of misinformation and fake news that it was considered an infodemic [Indeed, many professionals considered that they were overworking during the pandemic . Coherently, all the groups reported an average of more than six extra working hours the previous week, with the healthcare group showing the highest mean . Thenfodemic ). ConseqThe fear of infection is a concern commonly found in the literature about frontline workers during the COVID-19 crisis , and thWe are aware that the present study was not without limitations. First, the four groups selected do not represent all the possible frontline professionals working during the COVID-19 pandemic. By selecting only healthcare, grocery, mass media, and protective professionals, we missed other relevant frontline workers such as those related to transportation services or finances. Second, the sample sizes were not equal in all the groups. Less than 100 workers participated in the groups of grocery workers and protective service professionals. Finally, the online recruitment may have influenced data collection, since it may have discouraged older workers to participate in the study. Due to the above-mentioned reasons, the findings of this study should only be generalized with caution.The results of this study can help make recommendations aimed at protecting mental health in frontline workers. First, special attention should be paid to healthcare workers, grocery workers, and media professionals, regardless of their previous experience in similar crises. Specifically, dedicated attention should be paid to females working in the healthcare and grocery sectors and to young media and protective service workers. Within healthcare workers, the most vulnerable professionals are those working in the most affected regions, tending to COVID-19 patients, and/or taking care of dying patients with COVID-19, so more intensive monitoring and measures might be applied to them. Second, acknowledging the potential differences between professional groups regarding how the progression of the crisis impacts their working conditions might also help to provide timely support. In line with other authors ,62 and iThird, human resource departments should also schedule frequent breaks for their employees and check and improve their workflows, as well as make sure that their employees regularly enjoy days off in order to reduce objective and subjective overload. Additionally, personal protection equipment should be provided to all frontline workers, as previously stated, to reduce their concerns about becoming infected or infecting others and thus lowering the psychological impact of the crisis. Fourth, frontline workers should also be provided with emotional training on emergency coping techniques by their employers, and easy access to psychological care should be provided to them or at least facilitated . In thisStrategically, a national network of psychological support with crisis intervention expertise should be integrated in the human resource departments of frontline workers’ institutions or, more generally, in the National Health Provision—at least during crisis periods—to provide specialized support and prevent the appearance of mental health issues. Importantly, psychologists providing crisis intervention should be proactive instead of waiting to be asked for help. This is essential to reach professionals that may hide their emotional state (such as protective workers in our sample) or those who traditionally delay their request for assistance  .In conclusion, our results show that the proportion of frontline workers showing high psychological impacts derived from working during the COVID-19 sanitary crisis is alarmingly high. This can be explained by the severity of the crisis but also by the failure of the hiring companies and the national health strategy to provide workers the necessary support. Indeed, despite the severity of the psychological impacts and the indicators of sadness in all frontline workers, psychological assistance was surprisingly absent for 90% of the sample. Therefore, letting psychologists who are experts on crisis management help heads of sections customize labor measures (as was done in China; see [


Parenteral nutrition (PN) is a complex and specialized form of nutrition support that has revolutionized the care for both pediatric and adult patients with acute and chronic intestinal failure (IF). This has led to the development of multidisciplinary teams focused on the management of patients receiving PN: nutrition support teams (NSTs). In this review we aim to discuss the historical aspects of IF management and NST development, and the practice, composition, and effectiveness of multidisciplinary care by NSTs in patients with IF. We also discuss the experience of two IF centers as an example of contemporary NSTs at work. An NST usually consists of at least a physician, nurse, dietitian, and pharmacist. Multidisciplinary care by an NST leads to fewer complications including infection and electrolyte disturbances, and better survival for patients receiving short- and long-term PN. Furthermore, it leads to a decrease in inappropriate prescriptions of short-term PN leading to significant cost reduction. Complex care for patients receiving PN necessitates close collaboration between team members and NSTs from other centers to optimize safety and effectiveness of PN use. Intestinal failure (IF), first defined in 1981 as “a reduction in the functioning gut mass below the minimal amount necessary for adequate digestion and absorption of food” ,3. ChronAt baseline, a comprehensive nutritional assessment is required to determine the hydration and nutritional status of a patient with IF and to calculate individual requirements. This nutrition assessment should incorporate aspects influencing intake, absorption, and expenditure, such as sex and age, the anatomy of the intestine , and weight, height, and body composition. For visual representation see The route, type, and duration of nutritional support depends on the patient, underlying disease, and stage of IF. In SBS, there are three clinical phases after surgery: the acute phase, adaptation phase, and maintenance phase, corresponding with different nutrition strategies ,27.The acute phase, directly following resection, is characterized by exclusive PN administration in a hospital setting. The intestine can recover and adapt, and hydration and nutritional status can be restored. In the adaptation phase, the ultimate goal of treatment is to increase enteral nutrition (EN) and wean from PN, since PN is associated with frequent complications such as IF- and PN-associated liver disease, central line-associated blood stream infections (CLABSIs), central line occlusions, central line-related thrombosis, metabolic bone disease, and fluid/electrolyte problems . The maiEach patient with IF that is malnourished, or at risk of becoming malnourished, will need artificial nutritional support in the form of EN and/or PN. The management of this nutritional support should be guided by an NST to improve quality of care . The conIn current society guidelines for both adults and children with IF, the management of HPN patients by an NST in centralized units is recommended by the ESPGHAN, ESPEN, ESPR, CSPEN, ASPEN, and AuSPEN ,43,44,45Several studies describe the effect of NSTs for patients suffering from IF on a variety of clinical outcomes which are summarized below. Studies were identified by performing an extensive search in PubMed in July 2019. Keywords included: intestinal failure, parenteral nutrition, multidisciplinary care (team), nutrition support (team), and intestinal rehabilitation program. Studies were included if they discussed the effects of a nutrition support team on patients receiving PN for IF. Furthermore, reference lists from relevant (review) articles were screened for studies missed in the primary search; relevant articles were included if they met the inclusion criteria.As stated in As early as 1980, a decrease in complication rate was seen in a group of hospitalized adult patients receiving PN managed by an NST compared with a group managed by a variety of physicians .p = 0.012). Furthermore, they reported fewer electrolyte disturbances after the implementation of the NST . Also, the authors reported on significantly less usage of potassium, phosphorus, and magnesium intravenous piggyback supplementation  [Braun et al. retrospectively assessed the effect of initiation of an NST among hospitalized adult patients receiving PN. The NST consisted of a physician , two registered dietitian nutritionists, a registered nurse and a nutrition support pharmacist. Mortality decreased after the initiation of the NST  that reported on the effects of a total parenteral nutrition (TPN) team on metabolic and electrolyte abnormalities in adults receiving short-term PN in hospital [n = 420 patients) reported fewer abnormalities in patients managed by a TPN team (members of the teams varied between studies) [n = 69 patients) did not report a significant difference in the total number of abnormalities [A systematic review by Naylor et al. published in 2004 included five studies  ,57,58,59malities .p < 0.05) [The positive effect of an NST on CLABSIs was observed in 78 adult patients who received PN on a surgical ward. NST consisted of a nutritional nurse (other members were not reported). Jacobs et al. describe a decrease from 24 to 3% in their cohort after initiation of an NST ( < 0.05) . A study < 0.05) .p = <0.05). Calculated cost savings was 50.715 British pounds in one year [Kennedy et al. also reported on the effect of an NST for adult patients receiving PN. After initiation of the NST mortality for patients receiving PN decreased from 43 to 24%  receiving PN in hospital for a mean duration 219 days. 48% of the children suffered from a motility disorder, 37% had SBS. The study showed a decrease from 11.5 CLABSIs per 1000 catheter days prior NST to 1.1 CLABSIs per 1000 catheter days after NST initiation. Authors did not report on an effect on mortality .p = 0.01). Other complications and mortality did not differ between the group before and after implementation of the multidisciplinary team [Diamond et al. reported on the effect of a multidisciplinary team for children with SBS that included representation from surgery, neonatology, gastroenterology, transplantation, nursing, nutrition, pharmacy, social work, and palliative care. Children experienced significantly fewer overall episodes of sepsis per month of follow-up after implementation of the multidisciplinary team  [The development of an advanced nutrition team for neonates with SBS  resulted in a decrease in mortality  .p < 0.05). No significant difference in weaning from PN was observed. The team consisted of dedicated pediatric staff in general surgery, gastroenterology, transplant surgery, nutrition, pharmacy, nursing, and social work [Modi et al. saw a similar effect on the survival in pediatric patients with severe SBS cared for by a multidisciplinary team compared to a historical control group with overall survival increasing from 70 to 89%  [Hess et al. also retrospectively identified the effect of a comprehensive clinical care team  on mortality after 2 years of diagnosis in children with IF (underlying disease distribution not reported)  .Oliveira et al. reported on reduced disease-related mortality after installation of a multidisciplinary intestinal rehabilitation program for children diagnosed with IF between 0–365 days with 0.6 deaths per 3 months (95% CI −1.23–0.02). No significant effect on CLABSIs or advanced liver disease was reported .Multivariate analysis showed a hazard ratio of 5.6 for risk of death if an adult patient was cared for by an inexperienced HPN team compared to an experienced HPN team. In children a hazard ratio of 2.5 for risk of death was observed if a nutritional care team was absent during management .p = 0.005) [A meta-analysis including 233 children performed by Stanger et al. in 2013 examining on the effect of multi-disciplinary rehabilitation programs for children with IF also found an increase in overall patient survival  .In short, in pediatric patients receiving PN, an NST results in fewer CLABSIs, overall episodes of sepsis, and lower mortality across various studies. The increased survival rate as a consequence of an NST differs between studies but is high.Several studies report on a reduction of inadequate use of PN after implementation of an NST. A reduction in the number of adult patients receiving short-term PN in both ICU and acute floor of a tertiary referral hospital and level 1 trauma center was observed by Parent et al. . The rate of patients with short-duration PN use (PN duration of <5 days) declined by 30% in the ICU . No data on mortality or clinical outcomes were reported [Another study reported a reduction in TPN use in critically ill adult patients of up to 78.6% after implementation of an NST. Also less PN bags were wasted (493 versus 34) and yearly costs for PN were decreased from $513,246 to 195,176 [Lee et al. reported that after initiation of an NST for adult patients receiving EN and/or PN for at least 72 h a higher percentage of goal energy  and protein (gram) provision was achieved (66.9 versus 86.2% and 67 versus 81.7% respectively). Goal energy and protein was calculated based on weight. Also, a decrease in days on PN and EN was observed. NST consisted of a physician, pharmacist, nurse, and dietician .p = not reported). It was shown that the reduction in PN use and complications represented savings of 245.000 euro/year [n = 233 children [p = 0.62) [Piquet et al. reported that initiation of an NST in a university hospital resulted in a 35% decline in PN use with a parallel increase of EN. Furthermore, the amount of CLABSIs decreased from 25/year to 3/year  i = 0.62) .In conclusion, an NST results in fewer short-term PN prescriptions for adult patients admitted to hospital resulting in significant cost saving. This effect is not described in children receiving long-term PN.It is shown that the initiation of an NST is associated with a decrease in mortality and in mechanical, septic, and metabolic complications for both pediatric and adult patients receiving either short- or long-term PN, and results in more appropriate PN prescription for adult patients receiving short-term PN. However, several methodological limitations of studies investigating the effect of NSTs should be taken into account. First, the majority of studies concerning NSTs are retrospective studies comparing a cohort of patients prior and post initiation of an NST. This imposes a significant risk of bias. Since two different time periods are compared, the observed effect cannot fully be attributed to the initiation of the NST. For instance, with improved catheter care and the advent of new lipid emulsions survival of patients has improved over time ,74. It sThe NSTs of the Amsterdam UMC Emma Children’s hospital and the Erasmus Medical Center Sophia Children’s hospital are embedded in an intestinal rehabilitation program (IRP). An IRP is an extended version of an NST for patients with IF which provides care with the goal to promote intestinal adaptation and to achieve enteral autonomy and oral feeding .The multidisciplinary IF teams of Amsterdam and Rotterdam provide care for pediatric patients with chronic IF on HPN, and the team of Amsterdam also for adult patients with both acute and chronic IF. The teams consist of nurses, nurse specialists, a physician assistants, a pediatric gastroenterologist, a gastrointestinal surgeon, pediatric surgeons, an endocrinologist, dietitians, a pharmacist, a pediatric hematologist and a PhD student. Several other specialists, such as interventional radiologists, gastroenterologists for adults, speech therapists, social workers, psychologists and pediatric endocrinologists are consulted regularly. Approximately 115 adults suffering from type 3 IF and around 80 adults suffering from type 2 IF, and 65 children on HPN are managed by the teams. Also children and adults that have weaned off HPN are followed up by the teams.For children, all patients/caregivers are trained in safely caring for the CVC and PN in hospital, prior to discharge with HPN. Adults are trained by homecare nurses. The IRP assesses the competence of the trained adult patient and determines whether homecare can be discontinued. Patients on HPN are seen at least twice a year at the outpatient clinic (in the first year after discharge more frequently). The outpatient consult is multidisciplinary, patients are seen by a physician, nurse, and/or a dietitian. In between outpatient consultations, patients are often seen in shared care by a general pediatrician, have phone consultations, give regular updates via email (for example the current weight of the patient) and can be seen earlier when indicated. Patients suffering from type 2 IF are seen every 6–8 weeks to determine optimal timing of reconstructive surgery.The IF teams of both Amsterdam and Rotterdam are easily accessible, 24 h per day. Parents and adult patients can contact the team for PN delivery, feeding strategies, recipes or clinical assessment. The PN solutions are delivered by the hospital pharmacy (tailor made PN) or by a facility company (standard bags prepared or unprepared).Monitoring of HPN patients involves medical and psychosocial evaluation. Annual screening includes physical examination, dietetic review, assessment of growth and body composition (with air-displacement plethysmography), laboratory monitoring , bone health , physical activity assessment), IF associated liver disease ) and renal disease, dental review, endocrinological assessment, and, additional for pediatric patients, consultation of a speech therapist, physiotherapist, and social worker.Twice a week, a multidisciplinary briefing takes place in which admitted patients and patients seen at the outpatient clinic are discussed. The pediatric IF team can be consulted by the clinicians from pediatric clinical wards if a patient is on PN for two weeks or more and not growing adequately. Adult patients from adult clinical wards including ICU are discussed on a weekly basis in the multidisciplinary nutrition team clinical round.The close collaboration between the teams of Amsterdam and Rotterdam enables the discussion of difficult cases and collaboration on research topics. Also, the two remaining IF centers from The Netherlands, being Nijmegen and Groningen , are involved in this collaboration. Twice a year, the four teams come together to discuss clinical practice and ongoing studies. For optimization of care, members of both IF teams are involved in research projects, development of international guidelines, and attend national and international conferences. These conferences provide the teams the opportunity to present their study findings, to keep up to date on the management of IF, to work on team building, and to start and maintain collaborations in research with other IF centers from all over the world. Both teams are involved in the recently established European Reference Network for rare Inherited and Congenital Anomalies (ERNICA)—Intestinal Failure working group. Since IF is a rare disease, international collaboration is vital to improve care through research.The care for both children and adults with IF is complex and requires expertise from different disciplines. Nutrition is the cornerstone of treatment in these patients that are dependent on short- or long-term PN. Clinicians should work together in an NST, consisting of at least a supervising physician , nurse or nurse specialist, dietitian, and pharmacist. NSTs support the improvement of outcomes concerning survival, electrolyte disturbances, and infections. Also, NSTs lead to a decrease in the inappropriate prescription of short-term PN. Prospective multicenter studies are needed to improve the quantity and quality of evidence concerning outcomes with NSTs in IF patients. Close collaboration between team members and also between IF centers is crucial in the management of patients with this rare and complicated condition.


In people with multiple sclerosis (pwMS), fatigue, weakness and spasticity may reduce mobility and promote sedentary behavior. However, little is known about the existence of possible differences in the way MS modifies the propensity to perform physical activity (PA) in men and women. The present study aimed to partly close this gap by means of quantitative analysis carried out using wearable sensors. Forty-five pwMS  and 41 unaffected age- and sex-matched individuals wore a tri-axial accelerometer 24 h/day for 7 consecutive days. Raw data were processed to calculate average number of daily steps, vector magnitude (VM) counts, and percentage of time spent in sedentary behavior and in PA of different intensities . Women with MS spent more time in sedentary behavior and exhibited a reduced amount of light intensity activity with respect to men, while MVPA was similar across sexes. However, in comparison with unaffected individuals, the overall PA patterns appear significantly modified mostly in women who, in presence of the disease, present increased sedentary behavior, reduced MVPA, number of daily steps and VM counts. The findings of the present study highlight the urgency of including sex as variable in all studies on PA in pwMS. Multiple sclerosis (MS) is a chronic immunomediated and neurodegenerative disease of the central nervous system (CNS) which is thought to be caused by an interaction of environmental, genetic, and epigenetic factors ,2. This A number of relevant differences in terms of impact of the disease on physical and psychological dimensions are also associated with the individual’s sex, besides the well-known disproportion in terms of affected population . Men arHowever, little is known about the existence of possible sex-related differences in amount and intensity of physical activity (PA) performed by pwMS, since few studies have explicitly considered sex as a main variable of interest. This aspect is of extreme importance because approximately 80 to 85% of pwMS complain about the presence of mild to moderate fatigue as well as some kind of gait impairment . Owing tThe scarce existing literature provides contrasting findings about a possible different impact of MS on amount and intensity of PA carried out by women and men with MS. Anens et al.  reportedSuch an apparent lack of agreement might be explained, at least partly, by several factors which include: unbalanced samples composed predominantly of women (in percentages ranging from 70% to 85%), variety of data collection methods , type of parameter selected as representative of PA  and participants’ disability level. Historically, self-reported data, in the form of diaries and recall questionnaires, have been the most widespread technique used to assess amount and intensity of PA owing to their low cost, easiness of use and versatility. However, such an approach suffers from poor reliability and validity, participant recall bias, interpretation of questions  and overOn the basis of the aforementioned considerations, the main purpose of the present study was twofold: (1) to investigate the existence of possible differences between women and men with MS in terms of amount and intensity of PA performed during a week, continuously acquired using wrist-worn wearable accelerometers and (2) to verify whether the disease has a stronger impact on men or women with MS. The latter aspect was analyzed through data comparison with a control group of unaffected individuals matched for age, sex and socioeconomic attributes. Such information should be useful in adding a sex perspective in the management of MS, especially as regards the design of training and rehabilitative programs to reduce sedentary activity and promote a healthy active lifestyle in pwMS.In the period March-November 2019, a convenience sample of 45 outpatients  presenting with relapsing–remitting MS, followed at the Regional Center for Multiple Sclerosis of Sardinia  were enrolled in the study following these inclusion criteria: diagnosis of MS according to the 2005 McDonald criteria ,33, whicFor some specific supplemental analyses, individuals with MS were also stratified into two groups according to their EDSS score as follows: mild disability  and moderate-severe disability . Six participants  reported the use of a walking aid on a regular basis.step counts (SC);vector magnitude counts (VM), which are composite measures of accelerometric counts considered a proxy for overall physical activity . VM is clevels of PA intensity classified into three categories according to the associated value of metabolic equivalent (MET), namely sedentary behavior , light intensity PA  and moderate-to-vigorous PA . Such a discrimination was carried out based on the cut-points for accelerometric counts per minute (cpm) proposed by Sandroff et al.  as reporEach participant was instructed to wear a tri-axial accelerometer  previously validated for use in pwMS ,35 for 7As these thresholds refer to experiments during which accelerometers were positioned at the hip, a correction  was applied to account for the wrist placement. In the analysis, we considered and included only acquisition days characterized by an overall wear time of at least 16 h.p = 0.05 and the effect sizes were assessed using the eta-squared (η2) coefficient. Univariate ANOVA was carried out as a post-hoc test by reducing the level of significance to p = 0.025 (0.05/2) for SC and VM and p = 0.016 (0.05/3) for the PA levels, after a Bonferroni correction for multiple comparisons. Supplemental statistical tests focused on SC and VM only were performed using a two-way MANOVA by considering sex (women or men) and group  as independent variables. All analyses were performed using the IBM SPSS Statistics v.20 software .A two-way multivariate analysis of variance (MANOVA) was carried out to explore the existence of a possible differential impact of the disease on men and women with MS considering as independent variables sex (women or men) and status (pwMS or unaffected). Dependent variables were SC and VM in one case and the three PA levels in the other respectively. The level of significance was set at Results regarding the absolute values (min/day) and the percentage of time spent in PA of different intensities, as calculated from the accelerometric data, are reported in p = 0.03, Wilks λ = 0.89, η2 = 0.10), status  = 7.66, p < 0.001, Wilks λ = 0.78, η2 = 0.22) and sex x status interaction  = 4.52, p = 0.006, Wilks λ = 0.85, η2 = 0.14) on SC and VM values. The post-hoc analysis  and VM counts ., VM counts were also found significantly higher in unaffected women with respect to men .MANOVA detected a significant main effect of sex  = 3.13, p = 0.03, Wilks λ = 0.89, η2 = 0.10). However. the post-hoc analysis revealed that the only significant differences involved women participants. Women with MS, regardless their disability level, performed a reduced number of daily steps with respect to unaffected .The statistical analysis carried out on daily steps considering the participants stratified into the three groups  detected a main effect of status  = 3.13, p = 0.006, Wilks λ = 0.86, η2 = 0.14), status  = 3.33, p = 0.024, Wilks λ = 0.89, η2 = 0.11) and sex x status interaction  = 4.03, p = 0.01, Wilks λ = 0.87, η2 = 0.13) on PA intensity levels. The post-hoc analysis (see p = 0.035) and also higher than men with MS . As regards LPA, unaffected women and men displayed similar levels, while men with MS exhibit a significant increase of LPA when compared to unaffected, passing from 23% to 27.1% (p = 0.029). Also, men with MS exhibit higher LPA than women . At last, unaffected women of our sample spent more time in MVPA than men  while the values become almost identical in people with MS. The decrease observed in MVPA for women (from 15.9% to 10.5%) was found statistically significant (p < 0.001).MANOVA also detected a significant effect of sex  = 4.46, ysis see  detectedThe aim of this study was to assess the existence of possible differences in amount and intensity of PA (quantitatively assessed using accelerometers worn for a consecutive week) performed by men and women with MS and to estimate the impact of the disease across sexes through comparison with a sample of age and sex-matched unaffected individuals. The findings partly support both hypotheses since women with MS exhibited a pattern of PA characterized by a significantly higher percentage of time spent in sedentary behavior and a lower percentage of time spent in light intensity PA with respect to men with MS, while a substantial similarity between groups was detected in terms of MVPA. Nevertheless, even the trend of the remaining variables, though not fully supported by results of the statistical analysis, concur in defining the picture of an overall lower engagement in PA for women with MS. Our data also suggest that the disease has a stronger impact on women, since a significant reduction in daily steps, VM counts, and percentage of time spent in MVPA, as well as an increase in sedentary behavior, were observed in women with MS with respect to those unaffected, while this phenomenon was not detected in men.Firstly, it appears important to discuss the results obtained for unaffected individuals, as they represent the reference basis for estimating the impact of MS on PA levels. It is commonly believed that men are more physically active than women , but sucIn this context, our results are in agreement with those of two recent large-scale studies involving more than 90,000 British  and 900 The pattern of PA calculated for pwMS, considered as a single group, is also generally consistent with data of previous studies, especially as regards daily steps and percentage of time spent in sedentary behavior and light intensity PA. In particular, the number of daily steps calculated in our sample, pooling both women and men regardless of disability level (9032 steps/day), or even considering it, was found quite similar to results in studies on European pwMS ,46,47, bIn terms of PA intensity, the percentages of SB (63 to 68% for men and women respectively) and LPA (20 to 27%) here calculated, were found fully consistent with those reported in previous studies which indicated values from 60 to 70% for SB and 27 to 37% for LPA ,43,44,55The analysis of changes in PA magnitude and intensity across men and women with MS suggest that the disease has a stronger impact on the latter, who experience larger reductions in VM counts, daily steps, and percentage of time spent in MVPA, and also tend to exhibit a more marked sedentary behavior. While this phenomenon probably originates from a complex interaction between physiological, psychological and environmental factors which may differ across sexes, some explanations of this may be formulated based on evidence reported in previous studies that explicitly consider sex as the investigated variable. In the general population, it is known that women with disabilities must cope with several barriers that may limit their engagement in PA such as fatigue, lack of time, difficulty in accessing proper facilities, financial constraints and lack of knowledge about how to exercise safely . In womeSome limitations of the study are to be acknowledged. Firstly, the accuracy of the GTX3 device in terms of calculation of number of steps and classification of the PA intensity might be, in some cases, influenced by the wrist positioning adopted during our experimental tests. In particular, since the wrist acceleration on the y-axis  is lower with respect to the value obtained for the typical positioning on the hip, it is possible that in some cases  some steps were not correctly detected ,65. AlsoAs regards the tested sample, it should be recalled that our participants were mostly individuals characterized by low-mild disability (60% of them had an EDSS score of ≤ 3.5) who lived in an inner-city residential area. Thus, generalization of the results presented here to different geographic and socio-economic contexts and to individuals more severely impaired should be performed cautiously. Also, most pwMS who participated in the present study were still engaged in part- or full-time working activities, but in our analysis, we did not include specific information on the type of working task . As a result, we were unable to specify whether superior levels of sedentariness were somehow associated with the performed job. At last, given the cross-sectional nature of the study, it is impossible to verify whether the sex-related differences observed here change in the course of the disease or not. Although the level of disability and duration of the disease were similar across men and women of our sample, it is to be considered that men usually take less time than women to reach the same impairment level, and thus that the trajectory of change in attitude to performing PA may be different for the two sexes. In this context, the results which refer to sedentariness should be further verified in future studies performed on larger cohorts, as there are factors  that arThis study investigated the existence of possible sex-related differences in both amount and intensity of PA performed by women and men affected by MS using objective quantitative techniques . Our initial hypothesis was substantially confirmed by the results, which show a pattern of PA for women characterized by greater sedentary behavior and reduced activity of light intensity with respect to men, while similar values of MVPA were found. However, when comparing data of pwMS with those of unaffected individuals, most significant changes involved women with MS, who exhibited increased sedentary behavior, reduced MVPA, number of daily steps and VM counts with respect to unaffected ones. Taken together, such findings suggest that changes in the propensity to perform PA caused by the presence of the disease observed in previous similar studies, are mostly driven by the peculiar impact of MS on women, given their majority in the tested cohorts. Although further studies on larger cohorts also composed of individuals with higher levels of disability are needed to confirm the trend observed here, our data confirm the urgency of including sex as a variable in all studies on PA in pwMS, as well as selecting, whenever possible, quantitative objective measurements of PA. These strategies would be of great benefit in planning adequate interventions, in terms of training, physical therapy and even lifestyle guidelines, tailored to individuals’ needs to maximize their effectiveness.


Background: Dependence is a significant health-related condition for older adults (OA) and implies that self-care is transferred to other people, the community or institutions. Recent studies have analyzed the relationship between out-of-pocket (OOP) healthcare expenditures and dependence. Nonetheless, these studies were not specifically designed to estimate the economic impact of dependence. Our aim was to estimate the total adjusted annual OOP healthcare expenditures in dependent older adults compared to independent ones. Additionally, we explore the potential combined effect of basic activities of daily living (ADL) and instrumental activities of daily living (IADL) dependence on OOP healthcare expenditures.Methods: Data comes from the cross-sectional study “Economic impact of physical dependence in older adults and the burden of informal care” conducted in 2018 with a sample of 735 community-dwelling older Mexican adults ages 60 and older. We used direct  and indirect costs to estimate the OOP healthcare expenditures associated with dependence. We applied the Katz scale to assess dependence in ADL and the Lawton scale to assess dependence in IADL. Two-Part regression models were used to analyze the relationship between dependence and OOP health expenditures.Results: Presence of ADL dependence represented a higher level of expenditure, 107% compared to non-dependent OA , and 97% for IADL dependence . The combined effect of ADL and IADL dependence (132%) was greater  than the effect of ADL or IADL dependence alone. In monetary terms, OA with ADL dependence had a total annualized mean OOP healthcare expenditure of $31,865 (Mexican pesos), OA with IADL $26,912, and combined ADL and IADL $39,520.Conclusions: ADL and IADL dependence are associated with the total annualized OOP healthcare expenditures. This association is even higher when both conditions are present together. These findings highlight the economic implications of the dependence for individuals, their families, and the health system. Given that current evidence on effective interventions to prevent dependence in OA is insufficient, future studies should be conducted to estimate their costs and determine what interventions work, as well as their effectiveness and cost-effectiveness in different sub-groups of the population, and how these might be appropriately implemented. Dependence is a significant health-related condition for older adults (OA), and its presence implies that self-care is transferred to other people, the community or institutions . The WorThe prevalence of dependence for OA populations in high-income countries ranges from 15 to 17%, while in low and middle-income countries it ranges from 3 to 16%. In Mexico, by 2012, 21.7% of OA had basic activities of daily living (ADL) limitations, and 5.1% were dependents  has occurred amid a fragile economy marked by high levels of poverty and limited access to health services and resources . In that [INSABI ]. Despit70 y más−70 and over, and now as the Programa para el Bienestar de los Adultos Mayores-Program for the Welfare of Older Adults) which consists of the bimonthly payment of 2,750 Mexican pesos (115 US dollars approx.), and is intended to be universal to all individuals 68 years of age or older  did not have health insurance and 53.5% did not have an economic pension . HoweverRecent studies have analyzed the relationship between out-of-pocket (OOP) healthcare expenditures and different health outcomes related to the functional capacity of the OA, namely frailty , multimoAlso, the combined effects of basic activities of daily living (ADL) and instrumental activities of daily living (IADL) dependence on OOP healthcare expenditures has not been explored. We have designed a study that expressly seeks to better understand the economic implications of dependence in the elderly. Our main objective was to estimate the total adjusted annual OOP healthcare expenditures in dependent older adults compared to independent ones. Additionally, we explored a potential combined effect of ADL and IADL dependence on OOP healthcare expenditures.Data comes from the cross-sectional study “Economic impact of physical dependence in older adults and the burden of informal care” conducted in 2018 with a sample of community-dwelling older Mexican adults age 60 and older . AccordiWe administered an extensive questionnaire to study participants to collect data on the expenditures related to medications, consultations, hospitalizations, laboratory studies, devices, prostheses, and loss of labor productivity. Direct  and indirect costs were both used to estimate the economic burden of dependence.We calculated total healthcare expenditures based on the estimation of cumulative costs found through the questionnaires. All costs were annualized for 2018. We grouped data in direct and indirect costs as described below.Medical and non-medical expenditures were estimated using a micro-costing analysis, which allows monetary valuing of the individual use of health resources and services by study participants. Medical costs included medical consultations, specialist consultations, medications (including vitamins), laboratory tests, and hospitalization. Non-medical costs included nursing services, devices , prostheses, and other costs .Loss of labor productivity (OA). We determined the economic loss of labor productivity in working OA by asking about the number of days of work they had missed due to health-related reasons.Loss of labor productivity in the household (caregiver or relative). We quantified the loss of labor productivity at the household level by asking relatives how much they thought they had lost on income due to caring for the OA.We operationalized the indirect costs considering the monthly loss of productivity for the OA and his/her carer/relative as follows:We applied two widely known instruments to evaluate the functional capacity of the OA: the Katz and Lawton scales. The Katz scale  assess dBased on the information about ADL and IADL, an OA was considered dependent if: (1) they were unable to perform at least one of the ADL or IADL, (2) he/she had a primary caregiver who provided assistance for ADL or IADL, and accompanied him/her to health facilities. Using these criteria, we generated two variables that define either ADL or IADL dependence combining the difficulties in performing ADL or IADL and the presence of a caregiver. These were operationalized as binary variables, where 0 = independent, and 1 = dependent.We included factors associated with healthcare expenditures in the literature , 27 as pSex , age, health insurance (yes = 1), retirement pension (yes = 1), schooling , paid job (yes = 1), marital status (married/cohabited = 1), area of residence .We included 19 indicator variables for each of the following conditions that were obtained from participants' self-report : hypertension, diabetes, hypercholesterolemia, heart disease , embolism, stroke or cerebral thrombosis, arthritis or rheumatism, bronchitis, or pulmonary emphysema, osteoporosis, kidney chronic disease, tuberculosis, cataracts (one or both eyes), urinary incontinence, prostate disease (men only), and cancer . With this information, we generated a count variable to express the total number of chronic conditions in each participant. This variable was included in our regression models as a proxy for the general health status.We measured this variable using two indicators: number of outpatient visits in the last 6 months, and the number of hospitalizations in the last 12 months.For SES measurement, we created an asset index following a standard approach proposed by the WHO to estimate the permanent income of the household through the ownership of goods and some characteristics of the housing –30. In pVariables were described using means (standard deviations) or proportions, as appropriate. In bivariate analysis, the following statistical procedures were used according to the characteristics of each variable: Chi-squared test for categorical data and Mann-Whitney test for continuous data. Exploratory analyses, including graphs (histograms and scatter plots), were also used to determine the probability distributions of the outcome variable. At this stage, we observed a considerable percentage of OA that did not show out-of-pocket expenses (30%), and the distribution of expenditure showed a right-skewed distribution, so in the multivariate analysis we used a two-part regression model , 31.In the Two-Part model, the outcome variable is analyzed in two phases. In the first part, a regression for dichotomous variables (logit or probit) is used to estimate the probability of incurring OOP health expenditures. In our case, we coded the dependent variable  as a binary indicator, where one equaled older adult that incurred OOP health expenditures and zero equaled those that did not. In the second part, to reduce the effect of skewness of healthcare costs, a linear regression model on the natural logarithm of this variable is applied to estimate the average expenditures among individuals that incurred health expenditures. In general, it is recommended the use of the natural logarithm of healthcare costs to reduce the effects of the skewed nature of this variable. Results are interpreted (β) as semi-elasticities . Finally, total expenditures for each individual are estimated by multiplying the probability by the average results obtained through the first and second parts of the model, using Duan's smearing retransformation to obtain fitted values .We further conducted several sensitivity analyses to check the robustness of our results. First, we examined the combined effect of ADL and IADL dependence on OOP health expenditures. The combined effect of ADL and IADL dependence was analyzed by creating a new dichotomous variable, where 1 reflected the simultaneous presence of ADL & IADL, and 0 the presence of neither. Second, instead of modeling mean of healthcare expenditures, we modeled the median of OOP healthcare expenditures using a quantile regression model , 34.p-values were reported. Differences were considered statistically significant if p < 0.05.All regression models were adjusted for variables described in the Covariates section. Statistical analyses were performed using STATA version 15.1 software . Ninety-five percent confidence intervals and SD = 8.4 years). 57.8% were female, 56.0% married/cohabited, and 31% current workers. Mean of years of formal education was 4.2 (SD = 4.4). Regarding health characteristics, 63.4% reported at least one chronic condition, and 32.1% had multimorbidity, defined as the presence of two or more chronic diseases. Prevalence of ADL and IADL dependence was 8.6 and 15.0%, respectively.The following sociodemographic and health characteristics were observed in our sample. Mean age of participants was 71.1 years (p < 0.01), older (p < 0.01), and single or widowed (p < 0.01). They worked less (p < 0.01) and had fewer years of schooling (p < 0.01). They had more visits to a physician (p < 0.01), more hospital overnight stays (p < 0.01), and a greater number of chronic diseases (p < 0.01). Regarding OOP healthcare expenditures, dependent OA had a greater probability of incurring expenses than non-dependent OAs (p < 0.01) and also a higher annual mean expenditure (p < 0.01). This general profile was similar for ADL and IADL dependent OA. Finally, OA with ADL dependence had an unadjusted total annualized mean OOP healthcare expenditure of $29,272 (Mexican pesos), while the amount in OAs with IADL was $18,196.The results of OOP healthcare expenditures for specific items are shown in The results of the adjusted two-part regression models are presented in The presence of ADL dependence was associated with an 107% higher mean OOP health expenditure compared to non-dependent OA . This was 97% for IADL dependence . The combined effect of ADL and IADL dependence (132%) was greater  than the isolated presence of ADL or IADL dependence.With regard to the median of OOP healthcare expenditure, we found that ADL dependent individuals had a median annual expenditure $5,798 higher than non-dependent individuals (Mexican pesos), while the IADL dependent OA had an expenditure that was $1,844 higher than their non-dependent counterparts. This number was greater for the combined ADL and IADL dependence  .Finally, Our findings corroborate that there is a significant association between dependence in OA and OOP healthcare expenditures. Based on a sample of 735 community-dwelling older Mexican adults, we observed that the presence of ADL or IADL dependence as well as their combined presence was associated with a significant increase in the total annualized OOP healthcare expenditures.Consistent with previous studies, we found a significant association between dependence in OA and healthcare costs. One study with European older adults age 65+ found that ADL and IADL dependence were associated with higher societal costs . Although, this study measured ADL and IADL dependence on a continuous scale and was focused on societal costs rather than OOP expenditures . Even soDespite the similarity in the described results, we should note that none of the studies -to the best of our knowledge- on the economic impact of dependency have used the two-part model approach. This fact has two important implications. On the one hand, the results are not strictly comparable, given that those studies conceive of healthcare spending as a single-stage process . Meanwhile, the two-part model recognizes the potential presence of two phases: (a) to incur or not in healthcare expenditures , and (b) given the incidence of healthcare expenses, what was the amount disbursed? .On the other hand, we found that neither ADL nor IADL was associated with the probability of incurring OOP healthcare expenditures (even the two conditions combined). Although a similar result has not been reported in the literature, one study found that the severity of disability in older adults, assessed through the WHO Disability Assessment Schedule -WHODAS 2.0, was associated with a higher probability of healthcare expenses . Given tSistema Nacional de Cuidados, SNC by its Spanish acronym) is currently being considered. The objective would be to provide public services that are accessible, pertinent, of quality, and sufficient to guarantee the right of all people to be cared for, and also the rights of caregivers . All participants were provided with a detailed explanation of study procedures and signed an informed consent letter.AS-R, BM-E, and JM-H conceived and designed the study. AS-R and JM-H carried out the analysis. AS-R, IT, and JM-H drafted the manuscript. All authors reviewed, edited, contributed to rewriting of the manuscript, and granted final approval to the version submitted for publication.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-cause mortality did not increase in patients with DVT . On multivariate analysis, weight , and metastasis  were predictors of all-cause mortality. In conclusion, low weight and presence of metastases were associated with all-cause mortality, while presence of concomitant DVT was unrelated to poorer survival.In symptomatic acute pulmonary embolism (PE), the presence of deep vein thrombosis (DVT) is a risk factor for 30- and 90-day mortality. In patients with cancer and incidental PE, the prognostic effect of concomitant incidental DVT is unknown. In this retrospective study, we examined the effect of incidental DVT on all-cause mortality in such patients. Adjusted Cox multivariate regression analysis was used for relevant covariates. From January 2010 to March 2018, we included 200 patients  who were followed up for 12.5 months (interquartile range 7.4–19.4 months). Of these patients, 62% had metastases, 31% had concomitant incidental DVT, and 40.1% ( Venous thromboembolic (VTE) disease includes pulmonary embolism (PE) and deep venous thrombosis (DVT); however, these manifestations of the same disease have different clinical courses and prognoses ,2. The mn = 290) had PE with or without DVT. However, it was not possible to determine how many patients had concomitant incidental DVT.VTE is the main manifestation of the hypercoagulability state associated with cancer and is a leading cause of mortality and morbidity in patients with malignancies ,18,19. SWe aimed to assess the incidence of concomitant incidental DVT in patients with cancer and incidental PE, and to evaluate the association between the presence of concomitant DVT and mortality risk in this group.In total, we evaluated 234 patients with incidental PE, 34 of whom were excluded because they did not have a diagnosis of cancer . In the A comparison of patients with and without DVT indicated that those with concomitant DVT had a significantly higher prevalence of metastasis . Furthermore, at the time of the diagnosis of incidental PE, 75.8% of patients with concomitant DVT were receiving oncological treatment compared with 62.3% in the DVT-free group . The most frequent cancer treatments involved antimetabolites (47.5%), followed by platinum-based agents (35%). Among patients with cancer who had undergone treatment, 22.5% had been prescribed one drug, 33% had been prescribed two drugs, and 11% had been prescribed ≥3 drugs. Patient characteristics according to survival (no-death vs. death) are shown in p = 0.992; p = 0.97).Data were available for all patients at the end of the study. Of the 200 patients, 81 (40.5%) died during follow-up (95% CI 33.6–47.7%). Among them, 6% (95% CI 3.1–10.3%) and 15.5% (95% CI 10.8–21.3%) died at three and six months, respectively. Four patients  died of possible PE. There were 28 deaths  and 53 deaths  in patients with and without concomitant DVT, respectively. At six months, there were no differences in cumulative mortality in patients with incidental PE with and without incidental DVT  and the presence of metastases  at the time of incidental PE diagnosis showed significant associations with death during follow-up (p = 0.032) and the presence of metastases  continued to show associations with poor prognoses.In the univariate analyses, weight (per kilogram) , and among them, 12 (57%) were symptomatic. Most (53%) cases of VTE recurrence were associated with PE. Bleeding occurred in 15 patients , and major bleeding occurred in two patients .In this study of patients with cancer and incidental PE, the presence of concomitant incidental DVT was not associated with poorer survival rates. One-third of patients with cancer and incidental PE also had incidental DVT. The prevalence of concomitant DVT in the study cohort 31%) was slightly lower than that reported in a series of patients with acute PE without cancer, in which the prevalence of ultrasound-detectable concomitant DVT varied from 39 to 63% 1% was sl,27. ThisSeveral recent studies have assessed the prognostic effect of concomitant DVT in patients with acute PE ,9,16,29.There is a paucity of data concerning patients with incidental PE compared with those with symptomatic acute PE. Although current evidence is largely derived from observational and retrospective data, incidental VTE appears to be associated with prognoses, in terms of recurrent VTE development, bleeding, and mortality, which are as poor as those for symptomatic VTE . In 2019In our study, metastases were associated with a higher frequency of incidental DVT . This finding is in line with previous observations in patients with cancer and VTE. An analysis of the California Cancer Registry found that the incidence of VTE was higher among patients with metastatic disease . This ca2) was associated with a lower risk of all-cause mortality [p = 0.016) [n = 4010) [p < 0.001) and overweight  had a lower risk of all-cause mortality. Similar results were found in patients with VTE in a registry study that included 1642 patients with VTE and morbid obesity and 18,484 patients with healthy weight [The associations between weight, body mass index (BMI), and survival outcomes have previously been shown in other studies ,34,35,36ortality . In a rey weight . The finOur study had several strengths. First, once we had obtained initial evidence indicating that the presence of DVT could be associated with a poorer prognosis in patients with symptomatic acute PE, we then included performing a compression ultrasound of the lower limbs in patients with PE in the protocol. This allowed for the identification of incidental DVT in this population. Second, on analyzing the variables associated with mortality among patients with incidental PE, we included the most relevant factors, and we were then able to perform a multivariate-adjusted analysis.Our study also had some limitations. First, its single-center design may have limited the external validity of the results. Second, we did not find an increase in the mortality rates among the patients with incidental DVT. Even so, cancer is associated with several other factors that have a more decisive influence on patient survival ; therefore, for patients with cancer, there are many factors that could have had an effect on survival and that could mitigate the effect of the presence of DVT on survival. It is also possible that the sample size may not have been sufficiently large to identify differences in both groups (in terms of study power), and for that reason, larger prospective cohorts are needed. Third, the retrospective nature of the study could be associated with information bias; however, as above-mentioned, per protocol, we performed compressive ultrasound in patients with PE. Cancer types were not included in the model because the number of cancer locations was high and the number of patients in terms of the various locations was limited. We had no data on thrombophilic risk factors, although the association of thrombophilia with worse survival was not observed in the above-mentioned studies. We analyzed the role of weight as a predictor of death. A BMI analysis would also have been interesting; however, as we had no data on patient height, we were unable to analyze this variable. Although the incidence of thrombosis was low, we did not review the CT scans of the patients to determine whether thrombosis had occurred in other locations . Instead, our study focused on the effect of incidental DVT present in the lower limbs.This retrospective study used prospective data from consecutive inpatients and outpatients with VTE. The study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Virgen del Rocio Hospital, Sevilla, Spain . The requirement for written patient informed consent was waived due to the study design.The participants of this study were recruited from among the inpatients and outpatients of a respiratory ward at a teaching hospital in Sevilla, Spain, between January 2010 and March 2018.This study included consecutive patients with an objectively confirmed diagnosis of incidental PE, based on a positive chest computed tomography (CT) result. Patients who were unable to attend follow-up due to geographical challenges and those aged <18 years old were excluded. Histological confirmation was required for all patients diagnosed with cancer. Major bleeding was assessed according to the following International Society of Thrombosis and Hemostasis (ISTH) criteria: fatal bleeding, and/or bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular organs with compartment syndrome, and/or bleeding causing a fall in hemoglobin level of ≥20 g/L or leading to transfusion of two or more units of whole blood or red blood cells . The EasOnce the patients were diagnosed with PE, trained staff performed bilateral proximal and distal lower limb deep venous system compression ultrasonography in all patients at the time of their hospital consultation. The diagnostic criterion for DVT was the non-compressibility of a region within the deep venous system. In this study, all-cause mortality at six months after the diagnosis of PE was the primary endpoint. The secondary endpoints were PE-related mortality, VTE recurrence, and all-cause mortality at 30 and 90 days. Two investigators  reviewed and assessed all the outcomes. p-value of <0.05. The 95% CI was calculated using the Clopper–Pearson exact method. Binomial distribution using Statistical Package for the Social Sciences (SPSS) Statistics version 20.0  was employed, and all statistical analyses were performed using IBM SPSS Statistics version 24.0 software.Quantitative variables were expressed as means ± standard deviations. Medians and interquartile ranges (IQR) were used for non-normally distributed continuous data, and numbers and proportions for categorical data. We calculated Kaplan–Meier probabilities to estimate time to death and time to VTE recurrence, and a log-rank test was performed to assess differences between the groups. We censored for loss to follow-up (none) and study completion in the survival analyses. In addition, we controlled VTE recurrence models censored for death. To evaluate the association between concomitant DVT at the time of PE presentation, we performed a Cox proportional hazard regression analysis. In the full model, we included variables with a potential prognostic role in addition to the presence of incidental DVT. Backward stepwise regression was carried out to obtain the adjusted final model, with the variables selected in the equation in the last step. For all analyses, statistical significance was defined at a This study revealed that in patients with cancer with incidental PE, the presence of concomitant incidental DVT was not associated with poorer survival outcomes. One-third of all cancer patients with incidental PE were more likely to have an incidental DVT. The variables associated with all-cause mortality were low weight and the presence of metastases.


Ficus religiosa and Mimusops elengi were collected along with topsoil samples under the selected trees. Al, Ba, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, and Zn concentrations were determined by ICP-OES in soil and plant samples. Soils were not polluted according to the critical value; furthermore, the elemental composition did not differ among the sampling sites of the IURG. The rural site was also polluted due to heavy amounts of untreated wastewater of the adjacent Chao Phraya River. Bioaccumulation factors of Ba, Cu, and Mn was higher than 1, suggesting active accumulation of these elements in plant tissue. Our findings proved that the deposition of air pollutants and the resistance to air pollutants in the case of plant leaves were different and that humus materials of the soils had relevant role in bioaccumulation of Al, Ba, and Cu. At the same time, the geochemical background, the source of pollution, and the local plant species greatly influence the metal content of any given environmental compartment.Atmospheric aerosol particles containing heavy metal contaminants deposit on the surface of plant leaves and the topsoil. Our aim was to reveal the pollution along an industrial–urban–rural gradient (IURG) in the central provinces of Thailand. Leaf samples from  The proportion of urban population has been rapidly growing worldwide, and it is projected to increase in the future ,2. UrbanParticulate matter (PM) is a typical pollutant in urban areas; it is usually rich in toxic organic components and heavy metals ,9. Thus,Urban trees are used for indirect monitoring of PM and heavy metals in urban environments due to their distribution and cost-effectiveness . The accAlthough several authors studied the atmospheric deposition regarding both the quantities and elemental composition of dust ,23,24,25Soil organic matter (SOM) influences many soil parameters such as availability of nutrients and water management positively, and it is primarily responsible for soil fertility . SOM hasIn this work, urban, industrial and rural sites were selected in the central provinces of Thailand. The aim was to assess the variability of heavy metal content in tree leaves and topsoil at the selected sites. The rapid urbanization and industrialization in Thailand, particularly in the Bangkok Metropolitan Region, has led to an increase in emissions . The higFicus religiosa) and indian medlar (Mimusops elengi) were chosen because these species were found in all three sampling areas . Three individual trees were chosen randomly from each species, and 15 leaves were collected from each tree at 1.5 m high. Thus, we collected 90 leaves per sampling sites. At each sampling site, six soil samples were collected at a depth of 0–20 cm along the urbanization gradient from each sampling area from the same micro-location near the selected trees.There were three sampling areas  in Thailand . The indAfter sample collection, leaves were washed with tap waters . BecauseInductively coupled plasma optical emission spectrometry (ICP-OES 5110 Agilent Technologies) was used during the elemental analysis of leaf and soil samples. We used six-point calibration procedures with multi-element calibration solution (Merck ICP multi-element standard solution IV) and measured the concentration of Al, Ba, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, and Zn.2Cr2O7:H2SO4—1:1), the samples were boiled on a hot plate for 3 min. The cooled mixture was diluted to 100 mL with distilled water, and then, the residual dichromate was determined by titration with 0.2 N Mohr’s salt (Fe(NH4)2(S04)2.6H20) using ferroin as indicator. Soil humus quality was determined by the Hargitai method [NaF is the extinction value of the NaF extract, ENaOH is the extinction value of the NaOH extract, and H is the total humus content.Organic matter content was determined titrimetrically by the Tjurin method . One huni method . Dried si method . The extorg means the concentration of trace elements in leaves and Cm is the concentration of trace elements in the soil. Measured heavy metal content of the soils with hydrogen-peroxide and microwave digestion shows almost a total concentration. Some elements cannot be extracted with digestion; thus, we refer to them as extractable with strong extractants.The level of bioaccumulation is characterized with the bioaccumulation factor (BAF) defined as a ratio of concentration of trace elements in the plant and the concentration of trace elements in the surrounding environment ,39:BAF Statistical analysis was performed using the Statistica 7.0 statistical software package. Principal Component Analysis (PCA) was used to display the effect of tree species and urbanization on the elemental concentration of leaves and topsoil. The normal distribution was tested with the Shapiro–Wilk test. The homogeneity of variances was tested with the Levene’s test. The elemental concentration of leaves and soil parameters were compared based on the studied areas and tree species by Generalized Linear Model (GLZ) .Ficus religiosa was coded as 0, Mimusops elengi was coded as 1), humus content and humus quality (as independent variables), and the BAF values (as dependent variables). We applied two models, the multiple linear regression (MLR) and the multivariate adaptive regression splines (MARS) regression. While the MLR has the prerequisite of linearity and the normal distribution of the model residuals, MARS is a non-parametric extension of MLR without assumptions on dependent and independent variables. MARS algorithm runs linear regressions by partitioning the data into linear sections. MARS models are based on two steps. First, values of independent variables are partitioned into groups, and linear regression models are performed on all groups. Each group has a linear function with its own slopes and where the connections of lines are called the knots. All knots have two basis functions (BFs). In the second step, the algorithm uses these BFs as independent variables to provide a final model, removing the BFs that contribute the least [2 values, which is the correlation between the modelled and observed values of the data of the testing set. R2 values reflect the models’ efficiency and not the model fit. Statistical modelling was conducted in R 3.6.3.We analyzed the relationship of plant species  by plants species along the PC1 axis, while the sites of urban gradient had not significant differences, i.e., there was no spatial pattern of the elements  contributed 48.6% of total variance and the second one (PC2) contributed 18.1%. Element concentration in leaves had significant difference  according to GLZ. In the cases of other elements, the differences were insignificant. Usually, rural sites have the smallest metal loads due to smaller traffic and population density. However, in our case we note that the rural study site was alongside the Chao Phraya River, which is one of the major rivers of Thailand and is seriously polluted due to untreated wastewater originating from agricultural, industrial, and domestic activities [The elemental concentrations in the leaf tissue of the tree species were found to be homogenous across the study sites ; only intivities . Contamitivities . Fe is ativities . Howevertivities , where tFicus bengalensis, Alstonia scholaris, and Neolamarckia cadamba species are tolerant to air pollution, while F. religiosa is sensitive to air pollution. Trees with thin leaves such as F. religiosa can receive less particles due to their leaf position. Despite this, trees with hard leaves can trap more air pollutants upwards or horizontally with their concave surface [F. religiosa can be used to intercept air pollutants. Based on the elemental concentration of leaves, we demonstrated that M. elengi is a more tolerant species than F. religiosa. M. elengi leaves include pericyclic fibers, rosette and prism shape calcium oxalate crystals, and resinous matter [M. elengi exhibited more resistance to air pollutants than others such as Acmena accuminatissima, Lysidice rhodostegia, Bombax malabaricum, and Hibiscus rosa-sinensis. Similar to earlier findings, our results indicated that the deposition of air pollutants and the resistance to air pollutants of plant leaves vary with structure, geometry, height, and canopy of the tree. Thakar and Mishra [Nandy et al.  noted th surface . Prajapa surface  also dems matter . Changlis matter  reportedd Mishra  demonstrThere are numerous reports studying the heavy metal content of soils under anthropogenic influence. The first component (PC1) contributed 85.0% of total variance, and the second one (PC2) contributed 6.8%. There was no separation of sites based on soil elemental concentration .Unlike earlier reports , our finThe available proportion for plants can be lesser due to soil characteristics  and the type of binding (adsorbed or within solid phase), and depending on the physiology of the given species, the accumulation varies even by the organs ,63,64,65F. religiosa. While for Mn, higher BAF values than 1 were found in the industrial and urban sites based on M. elengi leaves. The BAF values of Cu and Mn were higher than 1 indicating that these elements could be accumulated in leaves from soil through any exposure route. Plants ingest heavy metals from 25 cm of the soil where the underlying foundations of most developed species are found [The BAF values were lower than 1 for all studied trace elements, except Cu and Mn . In the re found . Cu and re found ,67,68. G2 medians > 0.4), while in the case of Fe and Mn, the R2 medians were around 0.2, but the interquartile range indicated that the models can be more accurate in several cases. The relationship was the weakest in the case of Zn, with lowest upper quartiles. Results also pointed to the relevance of a robust approach, which came from the distribution: MARS was a better predictor algorithm than MLR. Splitting the database resulted in non-linear connections between the humus and the studied elements; thus, the MARS algorithm having no assumptions on distribution on the input data was more successful with better performance  regarding the heavy metal content of their soil environment to reveal the pollution level. We determined that F. religiosa accumulated significantly higher metal content than M. elengi in the leaves in the cases of Ba, Ca, Cu, K, Mg, and Zn, while M. elengi had higher metal content in the cases of Al, Cr, Fe, Mn, Na, Ni, and Pb. According to the multivariate analysis, the species had a significantly different accumulation pattern. The location, the industrial–urban–rural gradient, had not significant difference regarding the metal uptake, i.e., the intensity of land-use had no discriminating effect which can be in connection with the polluted Chao Phraya River near the rural sampling site. Bioaccumulation (BAF) was significantly larger in F. religiosa especially in the industrial and rural sites. We revealed that the multiple linear regression was not as efficient in finding the relationship between metals SOM and the humus quality as the MARS regression which has no assumptions regarding linearity, distribution, and outliers. The applied k-fold cross-validation provided more reliable results related to a correlation because it uses a training and an independent testing dataset, and the repetitions provided 50 R2-values which showed the range of possible realizations instead of a single value. We proved the connection between bioaccumulation and humus in case of Al, Ba, and Cu. Our findings demonstrated that trees are a useful indicator of air pollutants for biomonitoring studies of cities.Distribution of heavy metals in the environment is relevantly affected by biotic and abiotic factors. We analyzed two species’ (