The impact of primary site surgery on survival remains controversial in female patients with stage IV breast cancer. The purpose of this study was to investigate the role of primary tumor surgery in patients with stage IV breast cancer and concurrently develop a nomogram to identify which patients will benefit from surgery.We retrospectively searched the SEER database for female patients newly diagnosed with stage IV breast infiltrating duct carcinoma (BIDC) between 2010 and 2015 and then divided them into surgery and non-surgery groups. The propensity score matching (PSM) method was implemented to eliminate the bias, and Kaplan–Meier survival analysis was generated to compare the overall survival (OS) and cancer-specific survival (CSS) between the two groups. After PSM, Cox regression analyses were performed to determine the independent protective value of primary tumor surgery, while logistic regression analyses were utilized to uncover significant predictors of surgical benefit and establish a screening nomogram for female patients with stage IV BIDC. Nomogram performance was evaluated by calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).5,475 patients with stage IV BIDC were included in this study, and 2,375 patients (43.38%) received primary tumor surgery. After PSM, the median CSS was 53 months (95% CI: 46.84–59.16) in the surgery group compared with only 33 months (95% CI: 30.05–35.95) in the non-surgery group. We further found that primary tumor surgery was an independent protective factor for patients with stage IV BIDC. The independent factors affecting the benefit of locoregional surgery in patients with stage IV BIDC included histological grade, T stage, molecular subtype, lung metastasis, liver metastasis, brain metastasis, and marital status. The AUC of the nomogram was 0.785 in the training set and 0.761 in the testing set. The calibration curves and DCA confirmed that the nomogram could precisely predict the possibility of benefit from primary tumor resection.Our study suggested that primary tumor surgery improved the prognosis of female patients with stage IV BIDC and developed a nomogram to quantify the probability of surgical benefit to help identify surgical candidates clinically. Breast cancer (BC) is a common malignant tumor and the second most common cause of cancer death among women in the United States . Owing tSystemic therapy is the main treatment for stage IV BC patients to relieve symptoms, improve quality of life, and prolong survival, including endocrine therapy, targeted drug therapy, chemotherapy, and radiotherapy , 10. MorIt is well known that the histological subtype of BC can affect prognosis, with approximately 70%–80% of BCs being infiltrating duct carcinoma (IDC) , so we sThe data included in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The analysis of unidentified data in the SEER database did not require informed consent and was exempt from medical ethics review. We retrospectively searched for the data of female patients with stage IV BIDC from 2010 to 2015 and conducted a retrospective study. Patients who met the following inclusion criteria were included into the research: (1) 20 ≤ age ≤80; (2) first tumor; (3) histologically diagnosed as IDC; (4) survival time ≥1 month; (5) demographic variables and tumor characteristics are all available. In addition, patients diagnosed with autopsy or death certificate were excluded from this study. Totally, 5,475 patients  were included to form a PSM cohort to explore the impact of locoregional surgery on survival in female patients with stage IV BIDC. Afterward, 2,375 patients in the surgery group were randomly divided into the training group and testing group in a ratio of 7:3. Patients in the training set were used to develop the model, and patients in the testing set were used to validate the performance of the model.Statistical analysis was conducted using SPSS 24.0 and R 4.0.2. All statistical tests were bilateral, and p < 0.05 was considered statistically significant. After stage IV BIDC patients were divided into surgery and non-surgery groups, the PSM method was implemented to construct paired matched samples of two treatment groups to balance confounding variables. More specifically, patients in the two groups were 1:1 matched on the logit scale, using variables of p < 0.05 to generate propensity scores, with a caliper value of 0.0001. Then, the differences of variables between the surgery and non-surgery groups (before and after PSM) were evaluated by the chi-square test. We determined overall survival (OS) and cancer-specific survival (CSS) as two primary endpoints in this research. OS was measured as the time from BC diagnosis to the date of death due to any cause (including BC) or the date of last follow-up. CSS was measured as the time from the date of BC diagnosis to the date of BC death or the date of last follow-up. Subsequently, the Kaplan–Meier (K-M) method with the log-rank test was generated to observe the differences in OS and CSS between the surgery and non-surgery groups. Additionally, univariate and multivariate Cox regression analyses were performed to assess the independent protective value of primary tumor resection, and to identify CSS-related independent clinicopathological factors.We hypothesized that not all female patients with stage IV BIDC would benefit from primary tumor surgery. Under this assumption, patients who received primary tumor resection were divided into two groups, the benefit group and the non-benefit group, based on the median CSS time of the non-surgery group after PSM (33 months). Then, the univariate logistic analysis was used to determine the factors affecting the benefit of locoregional surgery. Significant variables with p < 0.05 in the univariate analysis were incorporated into the multivariate logistic analysis to further reveal the independent predictors of surgical benefit for patients with stage IV BIDC. Subsequently, on the basis of the surgery-benefit-associated factors, we established a novel nomogram with the “rms” package, a simple, multivariate oncology visualization tool for predicting and quantifying outcome rates for individual patients , to idenMoreover, to further verify the applicability of the model in the absence of prospective research data, we assessed the performance of the nomogram in the PSM cohort. Based on the score of each patient calculated by the nomogram, we divided all female patients with stage IV BIDC into three groups: (1) Surgery-Benefit group; (2) Surgery-Nonbenefit group; and (3) Non-surgery group. Specifically, patients in the surgery group with a probability  greater than 50% were assigned to the Surgery-Benefit group, while others were assigned to the Surgery-Nonbenefit group. Finally, K-M survival analysis with the log-rank test  was implemented to compare the CSS status among the above three groups, so as to test whether the model could quantify the probability of surgical benefit and identify surgical candidates.. As shown in In total, 13,285 female patients with stage IV BIDC at initial diagnosis between 2010 and 2015 were included in this study and 5,475 met the criteria . As show. The distributions of grade, N stage, radiotherapy status, chemotherapy status, bone metastasis status, liver metastasis, and molecular subtype were unbalanced for patients in the surgery group before and after PSM, while grade, T stage, N stage, radiotherapy status, chemotherapy status, bone metastasis status, brain metastasis status, liver metastasis status, lung metastasis status, and insurance status were unevenly distributed for the non-surgery group.To eliminate the patient-dependent bias, the 1:1 matched PSM method was generated, and 2,056 female patients with stage IV BIDC  were included for the following survival analysis. Baseline characteristics, including age, race, primary site, laterality, histologic grade, T stage, N stage, radiation therapy, chemotherapy, metastatic site , molecular subtype, tumor size, insurance status, and marital status, were all balanced (p > 0.05), as seen in 2. The. To further investigate the prognostic role of locoregional surgery, univariate and multivariate analyses for CSS were implemented, and the result concluded that primary tumor resection was clearly an independent protective factor . Other than that, age, histological grade, T stage, site of metastasis , molecular subtype, and marital status could also independently affect the clinical outcome of patients with stage IV BIDC .The median OS time, median CSS time, and 1–5-year OS/CSS survival rate for the surgery and non-surgery groups (before and after PSM) are shown in . To furt. To furt. Based on the above seven independent factors, a novel nomogram was established to identify female candidates with stage IV BIDC for locoregional surgery  would benefit. For the rigor of this study, we deleted two types of patients (n = 563) in the surgery group who could not be determined as benefit or not, as follows: (1) CSS status = 0 and survival time < 33 months and (2) CSS status = 1 and survival time = 33 months. With this assumption, patients in the surgery group with a median CSS time of more than 33 months were categorized as the benefit group , while those with less than 33 months were categorized as the non-benefit group (748 patients). Thereafter, univariate and multivariate logistic analyses were performed to determine the independent factors influencing the benefit from primary tumor resection of patients with stage IV BIDC. The independent surgery-benefit-associated predictors for primary tumor resection included histologic grade (p < 0.001), T stage (p < 0.001), molecular subtype (p < 0.001), lung metastasis (p = 0.005), liver metastasis (p < 0.001), brain metastasis (p < 0.001), and marital status (p = 0.002) . Based o. As shown in . In addition, ROC curves were also generated for each independent predictor variable , and the results implied that the AUC of the nomogram was higher than the AUC of all predictors individually, in both the training and testing sets. Additionally, we further validated the screening nomogram in the entire cohort and obtained good results with an AUC of 0.778 . The calibration plot also presented good agreement, and DCA showed the prediction accuracy in a wider range .We drew ROC curves for the training and testing sets, with the AUC of the nomogram being 0.785 in the training set and 0.761 in the testing set . As show. As show. As show. As show. As show. As show. As show. The results showed that patients in the S-Benefit group had a higher survival advantage than patients in the Non-surgery group , whereas patients in the S-Nonbenefit group presented poorer CSS than patients in the Non-Surgery group . These data further confirmed our hypothesis that not all stage IV BIDC patients would benefit from primary tumor surgery, and some patients may even have shorter postoperative survival time.Moreover, to further verify the applicability of the model in the absence of prospective research data, we went back to the PSM cohort for application validation. As described before, 728 patients with stage IV BIDC were assigned to the Surgery-Benefit (S-Benefit) group, 300 patients were assigned to the Surgery-Nonbenefit (S-Nonbenefit) group, and the remaining 1,028 were in the Non-Surgery group. Subsequently, we generated the K-M survival curves with the log-rank test to verify the discrimination ability of the screening nomogram . For example, if a widow with stage IV BIDC presents liver metastases, T4, histological grade IV, and molecular subtype HR-/HER2+, she will have a total score of 246, corresponding to an OR value of 0.726 (<1), indicating that she may not obtain a survival advantage from primary tumor resection. The novel nomogram is expected to be an effective screening tool for quantifying surgical benefit in female patients with stage IV BIDC, which may help oncologists make clinical decisions.To apply the nomogram, we first draw a vertical line up from the corresponding point of each variable to obtain the corresponding score and then add up the scores of each variable and draw a vertical line down from the total score row to get the probability of benefit from primary tumor resection Approximately 6%–10% of female patients were diagnosed with stage IV BC , and aboThe conventional view is that resection of the primary tumor in patients with stage IV BC is not associated with prolonged survival (except in patients with bone disease), and surgery may be only considered for certain patients whose systemic disease is under control, mainly to improve quality of life (QoL) –26. HoweAlthough surgical interventions have shown better survival outcomes, whether all patients should undergo locoregional surgery needs further discussion, especially in patients with poor surgical tolerance. The unplanned subgroup of the MF07-01 trial found a survival benefit of breast surgery in young patients (<55 years) with bone metastases only and positive ER/PR status . In addiTo our knowledge, this is the first screening nomogram to quantify the probability of surgical benefit in female patients with stage IV BIDC and identify surgical candidates clinically. However, our study has some shortcomings. First, the information in the SEER database is not complete, such as surgical method, endocrine or targeted therapy status, and general health status of patients. Second, although the screening nomogram was established in the training set, and verified in the testing set, entire cohort, and PSM cohort, prospective studies are still needed. Third, as a retrospective study, only patients with stage IV BIDC at initial diagnosis were included, and metastatic disease that occurred in the latter stage cannot be identified, which may reduce some clinical guidance value.Our study suggested that primary tumor resection improved the survival of female patients with stage IV BIDC and developed a nomogram to quantify the probability of surgical benefit to help identify surgical candidates, which may help oncologists make clinical decisions.https://seer.cancer.gov/.Publicly available datasets were analyzed in this study. These data can be found here: ZQW, BC, and XXD conceived of and designed the study. JYC, ZXW, and HYG performed the literature search. BC and YW generated the figures and tables. ZQW and BC analyzed the data and wrote the manuscript. XXD critically reviewed the manuscript and supervised the research. 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.


Objectives: Inadequate oral hygiene still leads to many serious diseases all over the world. Therefore, this study aimed to analyze scientific research in the field of oral health in order to be able to comprehend their relevant subject areas, research connections, or developments. Methods: This study aimed to assess the global publication output on oral hygiene to create a world map that provides background information on key players, trends, and incentives of research. For this purpose, established bibliometric parameters were combined with state-of-the-art visualization techniques. Results: This study shows the actual key players of research on oral hygiene in high-income economies with only marginal participation from lower economies. This still corresponds to the current burden situations, but they are more and more shifting to the disadvantage of the low-income countries. There is a clear North–South and West–East gradient, with the USA and the Western European nations being the most publishing nations on oral hygiene. As an emerging country, Brazil plays a role in the research. Conclusions: The scientific power players were concentrated in high-income countries. However, the changing epidemiological situation requires a different scientific approach to oral hygiene. This requires an expansion of the international network to meet the demands of future global oral health burdens, which are mainly related to oral hygiene. The purpose of oral hygiene is to prevent the formation of plaque, which indexes caries, gingivitis, and periodontitis . The redOral health refers to the freedom from inflammation and discomfort of the tooth, mouth, and jaw system and is therefore a critical part of general health and quality of life .The Global Burden of Disease Study 2017 estimated that oral diseases affect 3.5 billion people worldwide . SeriousStill, most people in developing countries do not have access to oral health programs . NeverthThe focus of scientific research in the field of oral hygiene is on oral disease prevention and reduction of the burden on health systems, which is estimated as 5% . In addiSince poor oral hygiene as a key factor for oral health still causes suffering for many people worldwide and is additionally associated with high financial societal burdens, it is necessary to take an in-depth look at relevant research efforts. Therefore, this study aimed to conduct a thorough evaluation of the research from chronological, geographical, and socio-economic aspects. The results thus provide background information for future planning of research programs, targeted promotions, and meaningful measures to increase individual awareness of the importance of good oral hygiene.The applied methods are embedded in a methodological platform that combines established bibliometric approaches with advanced parameters and the inclusion of density equalizing map projections (DEMP ) for theThe core collection of the online database Web of Science (WoS) served as the most suitable data source because it also provides citation figures via its Journal Citation Report (JCR).The date of the retrieval of data was 10 June 2016. In order to include only full years in the analyses, the evaluation period was set from 1900 to 2015.The following string of search terms was searched in the title of the articles:  AND (clean* OR hygiene* OR rinse OR wash* OR brush*)) OR toothbrush* OR toothpaste* OR “dental floss*” OR “dental silk” OR “plaque removal” OR “interdental brush*” OR dentifrices OR “plaque removal” OR ((caries OR periodontitis OR gingivitis OR tartar) AND (preventi* OR prophylaxis*) OR [(fluoride* AND (varnish* OR “mouth rins*”)] NOT TITLE: .This complex search term ensured that articles on cleaning methods, cleaning tools, and cleaning instruments were found but not articles on plaque indices, dental instruments, and nutritional behavior. Subsequent filtering for original articles as the document type meant that only original studies were included in the analysis. The representativeness of the included articles was ensured by extensive random checking of the article list.The bibliometric meta data of the identified articles were downloaded from the WoS. Data were then sorted according to the various analysis parameters and stored in a Microsoft Access database. Some analysis categories, such as institutions, had to be manually standardized because different values are used.POP, RGDP).The subsequent generated database was analyzed according to a variety of parameters, such as time of publication, country of origin, number of citations, citation rate, publication source, and research field. Additionally, country-specific data were analyzed in terms of their socio-economic characteristics  in USD 1000 billion) . For thiCorrelations between publication year and publication numbers or citation numbers were calculated using Spearman correlation.Geographical results were visualized based on the established DEMP technique by Gastner and Newman using the ArcGIS application . This prInternational collaborations were depicted as networking diagrams represented by nodes and connecting lines of varying strength.n) were published in the WoS.In 115 years, a total of 4812 oral hygiene-specific articles (p < 0.01). The average number of studies increased from n < 100 per year until 2001 to n < 200 until 2010 and subsequently raised to >200 after 2011, with quantitative peaks in 1964 and the 1980s. The number of citations (c) increased continuously from c > 100 in 1961 to c > 1000 in 1971 and c > 2000 after 2000 (p < 0.001). In 1946 (n = 131), 1950 (n = 116), and 1964 (n = 1014), the number of annual citations was above the quantitative average. The maximum value (c = 2235) was reached in 2009, followed by a steady decline in the annual citation frequency , followed by the UK , Germany , Spain , and Israel . Outside North America and Europe, Brazil  produced the most oral hygiene articles , followed by the UK , Sweden (c = 6680), and Germany (c = 3920) B.Additionally, the average number of citations per article (citation rate = cr) of the countries with at least 30 articles on oral hygiene (threshold) was calculated. Denmark (cr = 25.9) showed the highest value, followed by Sweden (cr = 24.2), Norway (cr = 20.1), New Zealand (cr = 19.0), and Canada (cr = 17.2) C.POP) [POP = 28.4), followed by Finland (RPOP = 26.4), Norway (RPOP = 22.5), and Denmark (RPOP = 18.1). Germany and the USA, countries with high publication numbers, dropped to position 12 (RPOP = 4.4) and 14 (RPOP = 3.9)  . Here, tP = 3.9) A.GDP), the Scandinavian countries again dominated. Finland (RGDP = 512.5) was ahead of Sweden (RGDP = 484.1), Denmark (RGDP = 296.3), Norway (RGDP = 231.9), and the UK (RGDP = 215.2). The high productive countries Germany and USA only ranked 13th (RGDP = 93.5) and 19th (RGDP = 73.1) (When the number of country-specific publications was related to the gross domestic product (GDP) in USD 1000 billion  Table 2Table 2 ( = 73.1) B.n = 282; 44.8%).In line with the highest number of published articles, the USA was the country with the most collaborations (n = 113), Sweden (n = 58), and Brazil (n = 54). The most productive international collaboration was identified between the USA and the UK, with 45 articles. In addition, the USA collaborated with Germany and Canada on more than 30 joint articles. Overall, the most active international collaborations were established with the USA. For Germany, the USA remained the main cooperation partner, next to the Netherlands, Switzerland, and the UK  were assigned to the subject area of dentistry, oral surgery, and medicine; followed by public, environmental, and occupational Health (n = 491); general and internal medicine (n = 195); pediatrics (n = 190), and chemistry (n = 118).Most articles  , as the n = 1274 out of 4812 articles) was identified as the most productive nation, followed by the UK (n = 634) and Germany (n = 361). The USA had previously been nominated as the most productive nation of dental publications [When country-specific oral hygiene research was analyzed, the USA  for systematic evaluation of oral health and quality of dental care, has led to the Scandinavian countries being among the “very low- and low-caries countries” .Most of the collaborative articles were produced by the UK universities Cardiff University, University of Bristol, and University of Wales, in collaboration with various US institutes. This research mainly focused on the caries-preventive effect of oral hygiene products such as toothpastes and mouth rinses . The almThe intensive research of the German Braun AG in Kronberg with the Optiva Corp. in the USA and UK accounted for studies on plaque reduction by electric toothbrushes and therefore contributed significantly to the technical development of oral hygiene .In summary, a regional concentration of articles was observed, with only five nations being responsible for more than 50% of the article production.Although broad international networking already exists, future research planning should be expanded to include currently underrepresented regions. Mutual benefit can be achieved through the exchange of knowledge and new approaches, especially with regard to education and improved awareness of oral hygiene.The results presented may be somewhat biased by the composition of the generated database due to the characteristics of the online database WoS, which is known to have a bias towards English articles. In addition, not all articles can be included in the analysis due to WoS’s stringent requirements for indexed journals. The title search strategy applied also reduced the size of the database. Another limitation that must be considered when interpreting the results is the correctness of the error-prone citation parameters.Nevertheless, the advantages of the database as one of the most used sources worldwide and the quality of the listed articles combined with the guaranteed representativeness of the search strategy justify this approach.The present study was conducted to obtain information on the global research output on oral hygiene. It was found that the current major players in oral hygiene research are high-income economies. Only marginal involvement of lower-income economies can be observed. Thus, the commitment of research efforts is clearly concentrated and corresponds to the existing high burden countries. Nevertheless, the situation seems to be changing with the adoption in the developing countries of the lifestyle of the industrialized countries, and thus health burdens due to poor nutrition will become apparent there as well. Future research must take these circumstances into account. This requires the expansion of the international research network, which should include these regions, so that appropriate measures can be taken there as well, based on sound science. These requirements should be taken into account by all stakeholders. Scientists, planners, funders, and stakeholders involved in science are therefore encouraged to align their research efforts with this changing situation in mind.


Background: Mind-body interventions may support the development of adolescents’ self-regulation and provide a protective effect against maladaptive outcomes, e.g., internalizing and externalizing problems. The present study aimed at evaluating the effects of mindfulness-oriented meditation training (MOM) and autogenic training (AT) on a group of healthy Italian adolescents’ character dimensions, emotional and behavioral difficulties. Methods: 72 adolescents were randomly assigned to MOM/AT conditions and tested before and after the 8-week trainings through self-report measures . Main analyses involved robust and repeated measures ANOVAs, carried out separately for character TCI and SDQ-A scales. Results: After trainings, we found increased levels of cooperativeness and reduced emotional symptoms. Changes in these dimensions were negatively correlated: the more participants increased in their cooperativeness the greater decrease they showed in emotional symptoms. Conclusion: Both MOM and AT enhanced a cooperative attitude in adolescents and helped reducing their emotional problems. Therefore, it may be useful to apply these mind-body interventions in school settings as they can have a protective effect on the well-being and psychosocial adjustment of youths, through fostering their character maturity and helping them to better regulate their emotions. Adolescence is a period of development and change for youths across multiple domains . ExposurSchool-based prevention programs offer a means of targeting a broad portion of the population at or before the peak emergence of critical conditions, especially with programs offered to all students, thus avoiding the disadvantages of selecting out at-risk individuals, e.g., lack of failsafe screening and potential stigmatization ,11. InteIn particular, mindfulness-based programs have been broadly theorized to improve SR of emotions, behavior, and cognitive processes. Mindfulness has been defined as “paying attention in a particular way: on purpose, in the present moment, and non-judgmentally” . The useTo further address this issue, the present study aimed to evaluate the effects of two mind-body interventions on adolescents, namely mindfulness-oriented meditation (MOM) and autogenic training (AT), a relaxation technique first introduced by the German psychiatrist Johannes Heinrich Schultz in 1932. AT consists of a series of relaxation exercises, in conjunction with verbal cues, to learn to regulate physical processes  to induce a state of relaxation. Both programs may positively impact adolescents’ psychosocial adjustment; more specifically, we predict that these types of training will show some beneficial effect in reducing emotional and behavioral problems in youth.Moreover, as shown in previous studies, cognitive, emotional and social experiences could be affected by personality characteristics. In this regard, we built on previous research suggesting the importance of personality traits as protective factors for adolescents’ well-being and psychosocial functioning and the usefulness of assessing these dimensions, especially in the context of interventions that may potentially enhance some character dimensions . AccordiThe research study involved seventy-two adolescents aged between 16 and 20 years recruited in two five-year high schools, located in two small cities of approximately 7000 and 14,000 inhabitants in the north-east of Italy . Students belonged to four classes: the 3rd and 4th grade of a technical high school, and the 3rd and 4th grade of a scientific and linguistic high school. The schools were randomly assigned to a MOM or an AT condition, resulting in one 3rd and one 4th grade class assigned to each training. The training programs were led by two expert instructors of mindfulness meditation and autogenic practices, who were both present in each group meeting . The participants were tested twice, before the beginning and after the end of the courses , through two self-report measures, the TCI and SDQ-A. Questionnaires were administered in groups in participants’ classrooms, in the presence of their teacher and a research psychologist. The courses were designed to be comparable and structurally equivalent; they lasted 8 weeks, during which participants attended a group session once per week. Group sessions for both training programs took place during morning school time, on consecutive days. All the subjects were invited to continue to practice daily at home and to record in a diary each individual session. This study was approved by the Ethics Committee of the University of Udine  and all procedures performed in the study were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments.Seventy-two adolescents aged between 16 and 20 years  participated in the study. In total, 69 participants completed the training and the research questionnaires. We thus excluded 3 participants who had not concluded the training or the research questionnaires. All participants were volunteers and were previously informed about the research purposes according to procedures reviewed by their schools. More specifically, the study methodology, aims and procedures were presented to teachers, parents and students in a school general assembly by the experts, with the opportunity to ask questions and seek clarification from the researchers. All recruited participants reported no past history of neurological or mental illness and had no previous experience with MOM and AT training or with the outcome measures used in the study.The mindfulness-oriented meditation training (MOM) ,51,52 waThe autogenic training (AT)  was struPersonality was assessed by the 125-item version of the self-report form of the TCI , adminisThe self-report form SDQ-A ,57 was uAll participants attending the MOM and AT programs were asked to complete diaries on daily practice. More specifically, they were asked to report daily if they practiced individually at home, for how long and at what time of the day. They were also free to report any comments or personal experiences about their practice that they might want to share during the following group discussion.p < 0.05 was used as a statistical threshold of significance. All analyses were conducted using JASP (version 0.16) and R (version 3.6.3) software.Continuous measures were summarized reporting mean and standard deviation of raw data obtained before and after trainings in the MOM and AT groups . One part = −2.691, df = 67, p = 0.009), but the two groups did not differ significantly in total practice time reported by participants .Before performing the main analyses, we compared the two groups in terms of attendance at group meetings and individual practice time: participants to the MOM group had, on average, 1.19 absences (sd = 0.90), while the mean for the AT group was 0.59 (sd = 0.93); the total individual practice time accumulated during the training was, on average, 500.69 min (sd = 217.20) for the MOM group, and 600.57 min (sd = 434.36) for the AT group. The MOM group had a significantly higher absence rate (p < 0.05). On the basis of two 2 (Session: Session 1 and Session 2) × 2 (Group: MOM and AT) ANOVAs using robust M-estimator and 2000 bootstraps carried out on C and ST scores, there was a significant main effect of Session for the C scale . Thus, MOM and AT trainings led to higher scores on the cooperativeness scale at Session 2 than at Session 1.A Shapiro–Wilk’s test showed that the TCI character scores of C and ST scales were not normally distributed at Session 1 in the AT group (p < 0.05). Furthermore, at Session 2, the SDQ-A scores of the EMO scale were not normally distributed for the AT group (p < 0.05).A Shapiro–Wilk’s test showed that at Session 1, the SDQ-A scores of the BEH, HYP, PRO scales in the MOM group, as well as the PEE scores in the AT group, were not normally distributed . Thus, after MOM and AT trainings, participants showed lower scores on the emotional symptoms scale.On the basis of five 2 (Session: Session 1 and Session 2) × 2 (Group: MOM and AT) ANOVAs using robust M-estimators and 2000 bootstraps carried out on each SDQ-A scale score , there was a significant main effect of Session for the EMO scale . The more participants increased in cooperativeness after the training the greater decrease they showed in emotional symptoms.With regard to correlations between the indexes of Session 2 minus Session 1 changes in cooperativeness (C) and emotional symptoms (EMO), we obtained a significant negative correlation between changes in C and changes in EMO , before and after the trainings. Globally after both training programs, we found an increased level of cooperativeness, involving the acceptance of others, compassion and forgiveness. Alongside these changes, after the trainings, both groups showed decreased emotional symptoms, such as often feeling unhappy and downhearted. Moreover, the change in cooperativeness was negatively correlated with reduction in emotional problems: the more participants increased in their cooperativeness the more they showed a decrease in emotional symptoms after training.Our study sample had already been investigated, at the “baseline” Session 1, in a previous study  that sheMindfulness and relaxation-based interventions based on autogenic training produced similar beneficial outcomes despite the different aims and techniques on which they focused, i.e., mindful awareness and relaxation practices, respectively. Similar findings emerged also in some previous studies ,60. The In general, the present results are consistent with what has emerged in previous research; implementing mind-body programs in schools can be an effective method to enhance positive intra- and interpersonal changes ,64,65, sOur findings also show the importance of continuing to assess personality traits and their relation to well-being and psychosocial functioning in adolescence . More spNotwithstanding these promising results, more studies are needed to clearly define the specific effects and processes of the action of autogenic and mindfulness training in young people. Deepening this line of research will help tailor more effective programs for specific age groups and conditions, e.g., evaluating which delivery aspects of mind-body programs, such as duration of training, level of expertise of teacher training, environmental aspects, home practice, etc., induce the largest effects. Training should also be specifically adapted for use with youth, by shortening practice periods, making language appropriate for youth, and selecting age-appropriate activities, but further research is required to identify the optimal age, content and length of programs. These further investigations could be helpful to increase our knowledge on how to implement mind-body interventions in school settings with the aim of improving or preserving adolescents’ psychosocial functioning and well-being, which is becoming more and more important considering the challenges our society is facing and will face in the future.The present findings should be interpreted in the context of some limitations. First, the exclusive use of self-report measures can be susceptible to socially desirable responding and these are sometimes considered less reliable than more objective measures, such as observation, in detecting, for instance, externalizing behaviors ,86. OtheThe aim of the present research was to investigate the impact of different mind-body interventions, specifically MOM and AT, on a group of Italian adolescents, by detecting potential changes in character dimensions, emotional and behavioral difficulties. Both training programs were effective in increasing participants’ level of cooperativeness, and in decreasing their emotional symptoms. These findings support the importance of implementing mind-body programs in schools as a valid method to enhance positive intra- and interpersonal changes in students. To conclude, it is suggested that consideration of the outcomes of this research could inspire future studies to further investigate the effectiveness and the underlying mechanisms of mindfulness and relaxation practices in young people, with the aim of promoting their healthy and harmonious growth.


Antimicrobial resistance is one of the many health challenges worldwide, particularly in resource-limited countries like Ethiopia. Increasing knowledge of health professionals can reduce the occurrence of antimicrobial resistance. In this study, we determined the antimicrobial resistance knowledge and examined the associated factors among the University of Gondar Hospital health professionals.p < 0.05.An institution-based cross-sectional survey was carried out. The samples were randomly recruited. Statistical analysis was performed by using the statistical package for social sciences (SPSS) version 20 after entering the data using Epidemiological information (Epi-Info). To identify associated factors, the authors executed binary logistic regression and multivariate analysis wherein the statistical significance was decided at Four hundred and twelve health professionals with ages ranging from 20-60 years and mean age of 29.9 years took part in the study. Fifty-three-point-four percent of participants were males. The majority of the total respondents  had good knowledge of antimicrobial resistance. It was found that being male , a work experience of 6–10 years , having 30–38working hours per week , and antibiotic intake  were significant factors of antimicrobial resistance knowledge.In the current study, about 84.5% of health professionals had good knowledge of antimicrobial resistance. Reducing working hours per week and increasing the experience of workers are recommended to increase the knowledge on AMR. Antimicrobial resistance (AMR) is one of the main global health challenges, particularly in resource-limited countries associated with increased antimicrobial use –7. The eThe role of health professionals is essential in the rational use of antimicrobials. Potential benefits of awareness of the effects of AMR for health professionals are helpful to prevent any kind of infection, reduce the occurrence of AMR, and promote effective drug use , 15, 16.As it is defined by WHO, rational use of antimicrobials is “the cost-effective use of antimicrobials which maximizes the clinical therapeutic effect, whereas minimizing both drug-related toxicity and the development of AMR , 19.” ToGlobally, the rate of AMR is growing and becoming a threat to public health, increasing healthcare costs. AMR can result in the reduction of drug efficacy, difficult patient treatment, or increase in cost. At times, it may be impossible to achieve a therapeutic outcome . In a yeAs there were no previous studies to investigate the knowledge of AMR among health professionals in Ethiopia, particularly in Gondar Comprehensive Specialized Hospital, we undertake this research which could be used as a baseline for researchers to fill the gaps of AMR challenges. Henceforth, this study assessed the knowledge of health professionals on AMR and associated factors in the University of Gondar Comprehensive Specialized Hospital, northwest Ethiopia.We conducted a cross-sectional survey among health professionals at the University of Gondar Comprehensive and Specialized Hospital from June to August 2020. The University of Gondar is located in the northwest Ethiopia, 728 km away from Addis Ababa, the Ethiopian capital City. The hospital serves for more than 5 million people in the catchment area. It has about 1,060 health professionals at the time of the study period.All health professionals working in diverse departments in University of Gondar Comprehensive Specialized Hospital were the source of the population.Health professionals who are in the department of nursing, pharmacy, medicine, laboratory, and midwifery, all working with diverse departments in the University of Gondar Comprehensive Specialized Hospital were the included in the study population.All health professionals  working at the University of Gondar Comprehensive and Specialized Hospital were included. Some health professionals were excluded due to low contribution to the prevention of AMR. Health professionals who had <6 months of work experience and were on annual leave were also excluded.The sample size was calculated using single population proportion formula with assumptions about the proportion = 0.5, 95% uncertainty interval, and margin of error (d) = 5%. By adding a non-response rate of 10%, the final sample size was 423. We used a simple random sampling technique for the selection of study participants to be included.We developed a pretested semi-structured, self-administered questionnaire from previously published studies , 7, 28 wThe measuring techniques was, as per stated in the WHO, the level of measurement of antimicrobial resistance of communities . Each paThe dependent variable was knowledge of AMR, while potential independent variables were sex, age, marital status, education level, duration of work experience, setting (working section), profession, working hours per week, presence of work stress, and self- medication practice.Emotional responses that occur when the requirements of the job do not match the capabilities, resources, or needs of the worker. Respondents were asked whether they face symptoms of work stress within a single question. They were to answer as none, low, medium, or high based on their subjective opinion.The high amount of work or working time given or assigned to do per day. Respondents were asked to answer as none, low, medium, or high based on their subjective opinion on their workload in the department.The use of medication or drugs to treat self-diagnosed disorders or symptoms by purchasing at a community pharmacy without the prescription of other health professionals and without following appropriate diagnosis by the health practitioner team. Respondents were asked to answer “yes” if they had ever used drugs/pharmaceutical products for themselves without prescription and “no” if otherwise.The knowledge of participants in classifying drugs/pharmaceutical products sold OTC (without prescription) based on safety, effectiveness, and appropriateness, i.e., assurance that the patient can manage without supervision . Respondents were asked to answer “yes” for this question if they knew this classification and “no” if otherwise.p < 0.2), we performed a multivariable analysis using odds ratio with its 95% CI to describe the strength of association, and a p < 0.05 to ascertain the statistical significance to describe the association between exposure variables with the outcome variable (knowledge of AMR).We used Epi-info 7.1 for data entry before exporting into SPSS version 20 for computing, recoding, and statistical analysis. Mean with standard deviation (SD) and frequency were calculated. Binary logistic regression was fitted to identify associated factors of knowledge of AMR. After checking for bivariable association  took part in the study. There was a 97.4% response rate. The participants' mean age was 29.9 years . The majority of participants (82.3%) held a Bachelor's degree. From the participants, majority (47.6%) were Nurse professionals, followed by pharmacy professionals (27.2%) and Midwifery (16.7%). Of the total participants, 58.3% had 2–5 years of work experience and 39.1% of respondents work for 39–43 h a week .From a total of 412 respondents, 349 health professionals  had good knowledge of AMR. Three hundred and forty-three (83.3%) health professionals reported that they have used antibiotics for self-treatment in their lifetime. Among these, 183 (53.4%) participants have taken antibiotics within a year. Only a few participants (17.2%) gained training regarding AMR. Of the participants, 225 (54.6%) participants reported to practice self-medication in their life .In the bivariable analysis, sex, work experience, working hours per week, work stress, knowledge of over the counter drugs, use of antibiotics, and self-medication practice were associated with knowledge of AMR. Finally, we found that knowledge of AMR was significantly associated with being male , 6–10 years of work experience , 30–38 working hours per week , and antibiotics intake  .As AMR is a major global health problem and health professionals are key stakeholders in the prevention and control of AMR during prescribing and dispensing antibiotics and related activities, the authors conducted the cross-sectional study that assessed the health professionals' knowledge on AMR , 31. In In this study, the respondents' knowledge on AMR was 84.7% (95% CI: 80.08–88.30), which is in line with other studies , 31–33. p > 0.05) in a previous study conducted in Dire Dawa, Ethiopia  even though they were the candidate variables for multivariate regression (p < 0.2).However, other studies showed that AMR is mostly developed by self-medication , 31, 34.Even though this study used a large sample size and was able to find possible contributing factors for health professionals' knowledge of AMR, it also had limitations including recall and social desirability bias. In addition, the cause-effect association cannot be elucidated by using a cross-sectional survey.The current study showed that 84.5% of health professionals had good knowledge of AMR. Male sex, high work experience, low working hours per week, and history of antibiotic intake were found to be contributing factors with good knowledge of AMR. Reducing working hours per week is recommended to increase the knowledge of AMR.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical approval was gained from the Ethical Committee of the School of Pharmacy, University of Gondar with ethical review protocol number: SOP/559/2019. All participants were informed about the purpose of the study. Written informed consent was obtained from each participant to assure their willingness of participation and no identifiers were listed in the questionnaire to make it confidential.WS involved in the proposal development, analysis, and manuscript writing. BD, HD, and BW participated in statistical analysis and manuscript preparation. All authors reviewed and approved the final manuscript.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. The reviewers AM and AS declared a shared affiliation with the authors, to the handling editor at the time of review.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.


U tests indicated that female caregivers consistently scored higher than male caregivers on COVID-19 stressors related to income, family, and chaos. Finally, concurrent validity was demonstrated by significant bivariate correlations between each scale and caregiver, family, and child outcomes, respectively. This demonstrates the validity of the COVID-19 Family Stressor Scale for use with female and male caregivers in family-based research. The current sample was predominantly White-European, married/common-law, and had at least some post-secondary education. Additional sampling and validation efforts are required across diverse ethnic/racial and socioeconomic groups.The COVID-19 pandemic has raised significant concerns regarding the effect of social disruptions on parental mental health, family well-being, and children's adjustment. Due to the pace of the pandemic, measures of pandemic-related disruption have not been subject to rigorous empirical validation. To address this gap, a multi-national sample  of 372 female caregivers and 158 male caregivers of 5–18-year-old children was recruited online. Participants completed a survey including a 25-item scale indexing disruption in finances, basic needs, personal and family welfare, career/education, household responsibilities, and family relationships related to the pandemic. An exploratory factor analysis yielded an optimal three-factor solution: factors included Income Stress , Family Stress , and Chaos Stress . Multiple-group confirmatory factor analysis demonstrated measurement invariance of each factor across female and male caregivers, indicating that factor structure, loadings, and thresholds were equivalent across groups. Composites reflective of each factor were computed, and Mann-Whitney  The COVID-19 pandemic has brought upheaval to families across the globe. There is widespread disruption to family life due to school closures, loss of access to regular childcare, social distancing, household crowding, economic recession and its associated consequences , and disruptions related to managing the pandemic such as  shortages of supplies and an influx of news/media coverage . Such soTo date, there does not exist an empirically-sound and comprehensive measure of family stressors related to COVID-19. Though COVID-specific psychological distress and mental health scales for use with adults have been validated , there iAnother problem related to family research during COVID-19 is the pattern—well-documented in developmental psychopathology—of omitting male caregivers from observational or survey-based studies . InclusiStandards for Educational and Psychological Testing . The CoFaSS was developed within a conceptual framework of COVID-19 disruption and family resilience, further described below . We foll Testing , the cur Testing . We util Testing .Next, we examine the resultant CoFaSS scales for internal consistency and their relations to other variables . With respect to the latter, we expect there to be mean group differences across male and female caregivers in social disruptions related to the pandemic, as captured using the CoFaSS scales. Concurrent validity is further examined within a theoretical model linking COVID-19 to child and family well-being . SpecifiThis endeavor addresses current measurement limitations, such as the use of non-validated scales and/or single-item metrics that do not adequately capture the variegated and cumulative ways in which the pandemic has disrupted life for families. The goal of this project is to inform how pandemic adversity is conceptualized, measured, and studied, while providing a practical tool that can be easily and reliably deployed in child, youth, and family research during times of international crisis.Child Resilience and Managing Pandemic Emotional Distress in Families Study (CRAMPED), a multi-national, longitudinal study examining family dynamics and sibling differences during COVID-19. Ethics approval for the current study was obtained from the research ethics boards of the universities of all listed authors. Recruitment for the larger study was conducted from an online research panel (Prolific®). Prolific® is a research company that facilitates online participant recruitment for surveys, including the targeting of specific populations, such as parents/caregivers, as is the case in the current study. This occurs through screening an ongoing pool of over 70,000 panelists worldwide. Based on availability of financial resources and statistical power, a target sample of 1,000 children in 500 families was established for the current study. The survey was launched in May 2020 and made available for approximately 1 week. Panel members from Prolific were initially screened based on a question determining if they had two children between 5 and 18 years given the study's goal of studying within-family processes in developmental psychopathology. Panel members who were eligible were invited to complete the study survey on Qualtrics®. There were 3,200 panelists screened, 626 who met inclusion criteria, and 549 who completed the survey within the time period that the survey was active. Panel members were remunerated based on the amount of time it took them to complete the survey . The survey for data included in the first wave of the study took approximately 56 min to complete. The average payout for the survey completion was $10.80 USD/participant. All questions were completed by a single caregiver, including questions on caregiver and child demographics, COVID-19 stressors, disruptions, and potential benefits, caregiver mental health and childhood experiences, family relationships and functioning, and child adjustment (for two children).Data come from the first wave of data collection of the M = 41.33, SD = 6.329), who reported on themselves and their children . Caregivers were mostly female (68%), married/common-law (90%), White-European (73%), and had at least some post-secondary education (69 %). The majority of the respondents resided in the United Kingdom (76%), with others residing in the United States (19%), Canada (4%), and Australia (1%). There was a wide range in annual household income prior to the pandemic , with the median value falling in the $50,000 to $75,000 USD range. Data on caregiver sex was extracted from the Prolific® database, with options of “male,” “female,” or “prefer not to answer.” Of the original sample, 530 caregivers elected to report on their sex . This subset of participants comprised the final sample for the current study. The current study only reports on measures involving the younger child.Participants included 549 caregivers  and members of their laboratory at the University of Waterloo, Canada, and was subsequently reviewed with critical feedback from the research team . The conceptual framework for the items was based upon a theoretical model of COVID-19 disruption and family resilience, which draws from systemic models of human development and family functioning, as well as empirical findings on the negative consequences of cumulative risk, human-made and natural disasters, global health crises, and economic recessions . In partNot True” (1), “Somewhat True” (2), and “Very True” (3)]. A “not applicable” option was not available for respondents. Items were scored based on respondent endorsements and there was very minimal missing data. Thus, for those items that were not applicable for participants, the default response was likely (1) . The internal structure, psychometric properties, and concurrent validity of the resulting subscales are presented in the Results.Items included stressors across domains of finances, basic needs, personal and family welfare, career and education, and household responsibilities. A list of all original items can be seen in Caregiver anxiety. The short-form, four-item, anxiety measure of the Patient-Reported Outcomes Measurement Information System  measureCaregiver psychological distress. The Kessler Psychological Distress Scale (K10) (None of the time” (1) to “All of the time” (5). Responses yield a global score of distress (α = 0.93).le (K10)  is a widParenting stress. Parents were asked the follow question: “Over the past 14 days, how stressful were your parenting experiences with [child name]?” and asked to respond using a seven-point scale ranging from “Not at all stressful” (1) to “Extremely stressful” (7). This item has demonstrated validity  to “Always” (5). A summed score was calculated (negative parenting practice items were reverse scored) and a higher score indicated greater positive parenting (α = 0.81).th Study . The carNever” (1) to “Almost Always” (5), α > 0.85 across domains.Caregivers reported on children's mental health problems using the parent proxy reports of the Patient-Reported Outcomes Measurement Information System (PROMIS®). The following domains were administered: anger  , anxietyWe used MPlus version 8.5 (2012–2020) to conduct the exploratory factor analysis (EFA) and tests of measurement invariance, and SPSS version 27 for descriptive statistics and analyses assessing concurrent validity. Minimal missing data were present (<1% for any variable).After removing low-frequency items, we subjected remaining items to an EFA (including 1–5 factors) in order to examine the underlying structure and interrelationships of scale items. This analysis used geomin rotation and the default weighted least squares estimator for categorical/ordinal indicators. We examined eigenvalues to identify potential factor solutions  and examined the empirical factor solution, in conjunction with conceptual accuracy, as the basis for grouping items into scales. Test of model fit relied on a non-significant chi-square value, as well as indices that are not sensitive to sample size including the comparative fit index (CFI ≥ 0.95) and the root mean square error of approximation (RMSEA ≤ 0.06) . We usedWe examined measurement invariance across caregiver sex to compare and contrast the latent structure of the CoFaSS scale for male and female caregivers, independently for each factor. We used multiple-group confirmatory factor analysis (MGCFA), wherein two nested models of varying restriction—a constrained model and an unconstrained (baseline) model—were compared for significant differences in model fit. The grouping variable was caregiver sex. If the model fit of the constrained model was not significantly worsened as compared to the baseline model, then invariance of the tested parameters was accepted . SpecifiFirst, we obtained the best factor model for each group separately by conducting independent CFAs. Mis-specified parameters were addressed following guidelines from Byrne . Once thU Test (due to the non-parametric shape of the data). We also examined the bivariate correlations between CoFaSS scales and several concurrent caregiver, family, and child outcomes, using Spearman's rho.Following tests of measurement invariance, scales were formed by summing scores within each factor, in addition to a general stressor scale including all items. Internal consistency of each scale was assessed by obtaining a Cronbach's alpha. Intercorrelations among all scales were examined using Spearman's rho. Relations of the CoFaSS scales to other variables was used as a test of concurrent validity. We examined whether the CoFaSS scales captured mean rank differences across male and female caregivers using Mann-Whitney r = 0.60 in the female caregiver group). Item 19 was retained for parsimony (due to its slightly higher factor loading). The final three factor solution included Income Stress (5 items with geomin rotation loadings ranging from 0.57 to 0.91); Family Stress (seven items ranging from 0.57 to 0.87); and Chaos Stress (four items ranging from 0.53 to 0.70). Items included in each of the three factors are denoted in p < 0.05).Distributions of item responses for the 25 scale items can be seen in the stacked bar plots in n = 158) and female (n = 372) caregivers. Fit statistics were acceptable for all factors in both male and female caregivers. In the Income Stress factor, freely estimated parameters of residual covariances were included for males (“Significant decrease [over 10%] in household income” and “Job disruption or loss [myself or my partner]”) and females , respectively, based on an examination of modification indices and theoretical justification. These two sex-specific estimates were included in subsequent invariance models involving the income factors.Results from invariance models can be seen in The least restrictive model of configural invariance, without any constraints, fit the data well for each of the three factors, indicating that the factor structure was invariant across male and female caregivers. There was one exception for the Chaos Stress factor in males only, with one of the two fit statistics above the cut-off (RMSEA = 0.094). An examination of the probability of the RMSEA being ≤ 0.05 indicated a value of 0.179, indicating acceptable fit .p < 0.005, suggesting worsened fit. However, the less sensitive cut-offs of ΔCFI and ΔRMSEA did not indicate meaningful change in model fit   , 39. Thurs = 0.27, p < 0.001) and Chaos Stress . Family Stress and Chaos Stress had a large association . Given the significant intercorrelations between factors reported in the EFA, as well as between composite scores, a General Stress scale was justified and computed .Composite variables based on summing of items were computed based on the final factor solution of the EFA. Each scale demonstrated acceptable internal consistency based on Cronbach's Alpha: Income Stress , Family Stress , and Chaos Stress . Spearman's rho correlations indicated significant associations among constructed CoFaSS composites: Income Stress significantly correlated with Family Stress . Female caregivers also scored higher than male caregivers on the Income Stress subscale, z = −3.09, p < 0.001 (difference in mean ranks = 44.12), the Family Stress subscale, z = −3.94, p < 0.001 (difference in mean ranks = 56.88), and the Chaos subscale, z = −5.10, p < 0.001 (difference in mean ranks = 73.43).Mann-Whitney The General Stress scale and each of the Income Stress, Family Stress, and Chaos Stress factors were correlated with constructs expected to relate to social disruptions from COVID-19, including caregiver , family  and child outcomes , including income reduction, debt, and job insecurity. Family-related stressors include those stemming from an increase in family altercations, emotional withdrawal, and child management concerns . A third cluster of concerns emerged related to chaotic states such as difficulties accessing essential supplies and/or exposure to COVID-19 news coverage . Thus, a particular clustering of stress may occur within individual families, with some strained due to financial insecurity, others due to the exacerbation of family issues arising from stay-at-home orders and social distancing measures, and still others that are due to disequilibrium of living during a time of severe public health threat. Differences in the sources of stress may have important implications for how families are impacted, pathways to resilience, and/or methods of intervention. Furthermore, the Income, Family, and Chaos Stress factors were significantly inter-correlated, suggesting that there may be an elevated climate of stress within families that stems from all three domains. In other words, these manifold stressors may aggregate together in some families, creating a particularly elevated threat to healthy adjustment and coping during the pandemic. Importantly, we might expect for the three types of COVID-19 stress to more frequently cluster in the most socially disadvantaged families, as has been demonstrated in studies of cumulative risk . It willThe emergence of three stress-related factors has important methodological implications for future family research. Specifically, the Family Stress factor indexes strain in family relationships and problems with child behavior management. This was reflected in the concurrent validity assessment wherein this subscale had the strongest associations with family and child outcomes among the three subscales. Future investigators can therefore decide when to use the General Stress scale or specific subscales based on specific study questions. For example, an investigation on the impact of pandemic-related stress on family processes may be better suited to using the Chaos and/or Income Stress subscales, so as to not conflate family stress with family process. As was demonstrated, use of the General Stress scale and/or specific subscales is a valid approach based on demonstration of reliability and concurrent validity, and should be tailored to specific samples, study designs, and research questions.Validation of the CoFaSS in both male and female caregivers was a primary goal of the current study. Configural, metric, and scalar invariance of factors provides evidence that the meaning of the CoFaSS scale is consistent across male and female caregivers. That is, the structure  and contribution of each item to the factor  were similar across male and female caregivers, and the mean differences in the factors captured all mean differences in the shared variance of the items. Such a demonstration—referred to as strong measurement invariance—is required prior to using a measure for sex-based analysis  . This reThe validation of the CoFaSS and generalizability of findings should be interpreted in light of the sampling approach used in the current study. The majority of participants identified themselves as White-European. As such, these findings are not generalizable to diverse ethnic groups and racialized communities who are disproportionally impacted by global crises including COVID-19 , 42. RelFindings also need to be interpretated within the regional and time-related parameters of the study. Data for the current study were from May 2020, relatively early on in the pandemic. As such, items that were removed due to low frequency of endorsements at this timepoint may indeed be relevant at different times of the pandemic. Relatedly, a large proportion of the sample was from the United Kingdom and the United States, with smaller numbers from Canada and Australia. Different countries, and regions within countries, varied in the timing and magnitude of the COVID-19 threat , as well as resulting policies . Limitations of our data, including measurement of the CoFaSS at a single time point, as well as small sample sizes within countries, preclude our ability to examine variations in stress over time or across regions. Given the ever-changing nature of the pandemic, it is important to consider the changing nature of family stressors. This is an issue that will be examined with subsequent data collection in the CRAMPED study.Finally, data were collected as part of a larger within-family study requiring participants to have two or more children between the ages of 5–18 years in the household. Further validation efforts will be needed to extend the use of the CoFaSS to caregivers of younger children and/or those with only one child as the experiences may not generalize to these groups. For instance, there is some indication for protective effects of having siblings in the home in the prediction of children's well-being during COVID-19 , 46.There are a few additional limitations that should be considered. First, caregivers reported on their own COVID-19-related stressors, caregiver, family, and child outcomes, thus raising the possibility of inflated associations due to shared-informant biases. Future validation procedures will be strengthened through a multi-informant and/or multi-method approach to address this threat to internal validity. Second, the readability of the scale items, as assessed by the Flesch-Kincaid Readability analysis, was a grade level of 9.6. This may limit comprehension amongst a broad range of groups, though at present is not considered prohibitive. Third, regarding validation procedures, additional sources of evidence for validity  were beyond the scope of the paper and should be considered in future validation efforts . FinallyThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by The Human Research Ethics Committee–University of Waterloo; The Human Participants Review Subcommittee–York University Ethics Review Board; Research Oversight and Compliance, University of Toronto. Participants provided electronic informed consent by selecting “Yes” on the following item: “Do you agree of you own free will to participate in this study?” If participants selected “No”, they were routed to an ineligibility message and were unable to participate.HP: conceptualization, analysis and writing. MW and JJ: reviewing and editing. SM: data collection and management and reviewing and editing. DB: conceptualization, methodology, data collection, and reviewing and editing. 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.


Rheumatoid arthritis (RA) is a progressive articular disease. In addition to damaging the joints, it may cause multiple organ complications, and considerably impair the patient’s functioning. Elderly patients with RA report pain, fatigue, mood disorders, sleep disorders and insomnia, accompanied by weakness, poor appetite, and weight loss. All these factors combined have an adverse effect on the patient’s perceived quality of life (QoL). Due to the chronic nature of RA and the high risk of malnutrition in this patient group, the present study investigated QoL, activities of daily living, and frailty syndrome severity in relation to MNA  questionnaire scores among elderly RA patients. The study included 98 patients (aged over 60) diagnosed with RA per the ARA (American Rheumatism Association) criteria. The following standardized instruments were used: WHOQoL-BREF for QoL, the Edmonton Frail Scale for frailty syndrome severity, MNA for nutritional status assessment, and MMSE  to assess any cognitive impairment. Medical data were obtained from hospital records. Patients with a different nutritional status differed significantly in terms of limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL). Higher levels of malnutrition were associated with greater limitations in activity. An adverse impact of lower body weight on cognitive function was also observed . Likewise, frailty was more common in malnourished patients . Malnourished patients had significantly lower QoL scores in all WHOQoL-BREF questionnaire domains than those with a normal body weight, and multiple-factor analysis for the impact of selected variables on QoL in each domain demonstrated that frailty was a significant independent determinant of poorer QoL in all domains: perceived quality of life (β = −0.069), perceived health (β = −0.172), physical domain (β = −0.425), psychological domain (β = −0.432), social domain (β = −0.415), environmental domain (β = −0.317). Malnutrition was a significant independent determinant of QoL in the “perceived health” domain (β = −0.08). In addition, regression analysis demonstrated the positive impact of male sex on QoL scores in the psychological (β = 1.414) and environmental domains (β = 1.123). Malnourished patients have a lower QoL than those with a normal body weight. Malnutrition adversely affects daily functioning, cognitive function, and the severity of frailty syndrome. Frailty syndrome is a significant independent determinant of poorer QoL in all WHOQoL BREF domains. Rheumatoid arthritis (RA) is a chronic polyarticular inflammatory disease affecting 1% of the total population . ApproxiElderly patients with RA next to malnutrition pain, report fatigue, mood disorders, sleep disorders and insomnia, accompanied by weakness, poor appetite, and weight loss. When combined, all these factors adversely affect the patient’s perceived quality of life ,13. The Due to the long-term chronic disease processes, many patients with advanced RA are elderly, which is associated with a risk of comorbidities typical for the elderly population. The most common ones include cognitive impairment, frailty syndrome, polypharmacy, and multimorbidity. The adverse impact of malnutrition on morbidity, mortality and QoL in a variety of diseases has already been recognized ,19,20. TQoL evaluation has become an important part of daily practice for physicians and nurses in recent years, and a topic of particular interest for many researchers. It may constitute an important endpoint in the evaluation of treatment outcomes. Approaching treatment effectiveness from the point of view of QoL has presented the medical community with an opportunity to demonstrate long-term effectiveness in the management of chronic diseases.The ongoing assessment of QoL is a multi-dimensional concept incorporating the individual’s perception of health status, psycho-social status and other aspects of life and rather concerns the impact of disease and symptoms on daily functioning and perception of health. Quality of life is assessed on the basis of physical, mental, social and environmental fitness, which refers to mobility, financial resources, access to medical care and the home environment. Additionally, questions are asked about the perception of health and quality of life. The purpose of our study was to analyze selected factors, including cognitive impairment, frailty syndrome, multimorbidity, the number of medications taken, and patient sex, in the context of malnutrition, and to evaluate their relationships with QoL in elderly RA patients.The study included 98 patients hospitalized at the Department of Rheumatology and Internal Diseases. The inclusion criteria were: age above 60 years, stable clinical condition and RA diagnosed per the ARA criteria . PatientThe study plan had assumed that patients would complete the surveys without assistance, but in some cases, due to the advanced age and vision impairment of some included patients, a nurse assisted the respondents in reading the questionnaire items whenever necessary. In all cases, the primary consideration was the unassisted provision of responses to all items.All elderly patients included in the study were evaluated on the basis of an interview questionnaire specifically designed for the purpose of the study, and a number of standardized scales. The MMSE questionnaire was used to evaluate cognitive function for the purpose of patient exclusion based on the pre-established criteria.The first stage of the study involved an interview used to collect general personal details and data on respondents’ socio-economic standing and health, and the MMSE assessment . During At the next stage of the study, 106 patients were evaluated for functional capacity, nutritional status, and QoL. At this stage, 4 patients dropped out, despite their prior consent to participate in the study, and another 4 patients returned incomplete questionnaires.All the remaining 98 patients were in a stable clinical condition. All patients consented to participate, having been informed that this was strictly voluntary and anonymous, and that they could withdraw at any time without providing a reason.The study was approved by the Bioethics Committee of Wrocław Medical University.The authors’ own questionnaire was used to collect data on patients’ sex, age, education, relationship status and residence. Clinical data were gathered from hospital records.We used the Folstein Mini-mental State Examination (MMSE) questionnaire. It is commonly used for dementia screening, allowing for rapid administration and straightforward interpretation of results . The MMSThe Instrumental Activities of Daily Living (IADL) scale was used to assess patients’ ability to perform complex daily activities. The scale evaluates eight parameters: using a phone, shopping, preparing meals, housekeeping, doing laundry, using transportation, taking medication, and managing money. Scores for each category range from 3 points—the patient is able to perform the activity with no assistance, to 1 point—the patient is entirely unable to perform the activity. The maximum score is 24 points, and the lower the score, the less independent the respondent . CronbacThe standardized, short version of the questionnaire is used for subjective QoL assessment in healthy or ill individuals, for research or clinical purposes. It provides a QoL profile including four domains: physical, psychological, social, and environmental. Scores in each domain are determined by calculating arithmetical means from all items contained in a given domain . Domain scores reflect patients’ individual perceptions of their QoL in each aspect. The Cronbach’s alpha coefficient for the original version of the WHOQOL-BREF scale was 0.896, and for the Polish version in the own study, 0.84  .® Mini Nutritional Assessment questionnaire (Nestlé Nutrition Institute), comprising a screening part and an assessment part. The former concerns appetite loss, mobility, weight loss over 3 months, BMI, and neuropsychological problems. The latter concerns diet , medication, self-reported nutritional status, and overall health. Calf and mid-arm circumference measurement is also included. The instrument has strict cut-off values, which has contributed to its widespread use in clinical practice worldwide. The assessment part comprises 12 items, broken down into anthropometric, general, dietary, and subjective assessment. Total MNA scores from both parts are used to identify patients with a normal nutritional status (≥24 points), at risk of malnutrition (17–23 points), and with protein-calorie malnutrition (<17 points) [All patients were tested using the complete MNA points) . MNA sca points) .For all patients included, we analyzed the correlations between nutritional status assessed using the Mini Nutritional Assessment scale and cognitive function, frailty, and WHOQoL-BREF scores. We also considered differences resulting from socio-demographic parameters, health status, and clinical parameters (number of chronic conditions). MNA scores below 17 points were used to identify malnutrition.For continuous or ordinal variables, data are presented as means and standard deviations, and as medians with interquartile ranges and ranges; for categorical variables, data are presented as percentages. Comparisons of categorical variable frequencies between groups were performed using the chi-squared test or Fisher’s exact test . Quantitative variable values were compared between two groups using the Mann–Whitney test. For three or more groups, quantitative variable values were compared with the use one-way ANOVA or the Kruskal–Wallis test . The effect of the MNA group on WHOQOL-BREF scores was analyzed with the use of ANCOVA with the age as covariate of WHOQOL-BREF. When a comparison showed statistically significant differences, post-hoc analyses were performed using the Bonferroni or Dunn’s or test, respectively. In the case of heavily left-skewed IADL scores, the effect of age was verified in a two-stage approach. Firstly, a linear regression model of the relationships between the age and IADL score was performed and the residuals were derived. At the second stage, the effect of MNA groups on the residuals  was tested with the use of one-way ANOVA. The relationships between selected variables and WHOQOL-BREF was analyzed with the aid of full multiple linear regression model. The Variance Inflation Factor (VIF) was used for checking the co-linearity of these explaining variables. The VIF ranged from 1.05 (Sex) do 2.38 (EFS), which proves the weak co-linearity of the variables. All analyses used a significance threshold of 0.05. The analyses were performed using the R software, version 4.0.4 , the G*Power software , and Statistica 13.5 .The MNA scores in our study were interpreted in accordance with the key and 57.14% patients were found to have a normal nutritional status, 36.73% were at risk of malnutrition, and 6.12% were malnourished. Further analyses were performed for groups identified on the basis of patients’ nutritional status.p = 0.001) compared to those RA patients who were well-nourished or at risk of malnutrition (p = 0.03). In the Bonferroni test, significant differences were observed between the Malnutrition group and the Normal nutritional status group p = 0.045).A comparative analysis of the socio-demographic characteristics of the patients studied and their nutritional status demonstrated that malnourished patients were significantly more likely to suffer from colorectal disease  of normally nourished patients had a full ADL capacity, while in the malnourished group, one in two patients, had a severely limited capacity to perform ADL.Patients with a different nutritional status differed significantly in terms of impairment in activities of daily living. IADL scores were heavily left-skewed in the groups analyzed and therefore, the Kruskal–Wallis test was used, and results were presented as medians, quartiles, and ranges.p < 0.001, p = 0.006, p = 0.73, respectively)  .p < 0.001). In the malnourished group, all patients had some degree of frailty, while nearly half of patients with a normal nutritional status had no frailty.Furthermore, the relationship between nutritional status and frailty syndrome was evaluated in the study sample. The results demonstrated an association between greater degree of malnutrition and greater severity of frailty in RA patients. Among the malnourished patients, 16.67% had severe frailty and the same percentage had moderate frailty, while in the normally nourished group, there was no severe frailty, and moderate frailty was only found in 3.57% of patients (p = 0.008).Our findings show that patients with a different nutritional status also differed significantly in terms of cognitive impairment, as more impairment was associated with poorer nutrition . Only hap < 0.05), and therefore, the Kruskal–Wallis test was used for analysis, and the results were presented as medians, quartiles, and ranges for each variable.WHOQoL-BREF scores did not have normal distributions in the groups analyzed  on each WHOQOL-BREF domain. Linear regression model findings are as shown in p < 0.05). For the “perceived health” domain, independent predictors included frailty and cognitive impairment. Each additional point in the EFS questionnaire decreased the QoL score in this domain by an average of −0.17 points (p < 0.001). For the physical QoL domain, frailty was an independent predictor. Each additional point in the EFS questionnaire decreased the QoL score in this domain by an average of −0.50 points (p < 0.001). As to medication (>3), it increased QoL in the domain by an average of 1.71 (p < 0.05). For the psychological QoL domain, independent predictors included frailty and male sex. Each additional point in the EFS questionnaire decreased the QoL score in this domain by an average of −0.36 points (p < 0.01). As to the male sex, it increased QoL in the domain by an average of 1.38 (p < 0.05), compared to female sex. For the social QoL domain, frailty was an independent predictor. Each additional point in the EFS questionnaire decreased the QoL score in this domain by an average of −0.34 points (p < 0.001). For the environmental QoL domain, independent predictors included frailty and male sex. Each additional point in the EFS questionnaire decreased the QoL score in this domain by an average of −0.61 points (p < 0.01), while male sex increased it by an average of 1.93 points (p < 0.05), compared to female sex. As to age, it increased QoL in the domain by an average of 0.18 (p < 0.01).For the “perceived QoL” domain, frailty was found to be an independent predictor of QoL. Each additional point in the EFS questionnaire decreased the QoL score in this domain by an average of −0.07 points (Our study demonstrated that among RA patients, health-related QoL as measured using the standardized WHOQoL-BREF scale was poorer in malnourished than in properly nourished patients. In addition, we found that poor nutritional status was associated with cognitive impairment and frailty syndrome severity, all of which adversely affected daily functioning and may in turn result in poorer nutrition. It is worth noting that in the regression analysis, the nutritional status was not a statistically significant factor affecting QOL, different to what we assumed in our study.Musculoskeletal disorders can result in a loss of the ability to work and lower QoL . Though Our study is one of only a few on the topic. Notably, hospitals have recently been obliged to assess patients’ nutritional status, but the results of these assessments are not widely used to evaluate patients’ functioning and treatment outcomes. The authors emphasize that malnutrition may result from improper nutrition .Malnutrition has been demonstrated to affect QoL chronically ill elderly populations , but issKremers et al. demonstrated that joint pain and fatigue in severe forms of RA were not the main factors contributing to QoL deterioration in RA patients with a low BMI . Severe,In our findings, the adverse impact of frailty syndrome on QoL was observed. Malnutrition-related loss of muscle protein leads to physical disability and limitations in ADL and IADL, which are characteristic of people with frailty syndrome . Tada etMarcora et al. claim that the implementation of rehabilitation and nutritional programs with protein supplementation may play a significant role in improving QoL in a frailty patient group. This may certainly also limit the adverse consequences of frailty . MarcoraIn our study, frailty was the strongest negative independent determinant of QoL in all the QoL domains studied. Salaffi et al., in a study on frailty in RA patients, demonstrated that this patient population was at very high risk of developing frailty syndrome. According to the authors, this may be related to the functional deterioration, depression, cognitive impairment, falls, malnutrition and polyphagia they ex-perience .Moreover, in our own study, we proved clearly that a greater degree of malnutrition is associated with a greater severity of frailty syndrome and cognitive impairment. Notably, concurrent frailty syndrome complicates patient management due to multi-morbidity and risk of progression all the way to irreversible disability . Bąk et Another independent determinant that had a positive impact on the QoL assessment in the psychological domain was male gender. The issue of gender as a determinant of QoL is often discussed and researchers lack a unified position. The available studies indicate a lower quality of life of the respondents, which may result from a negative attitude to pain and the occurrence of deformities. In women, the disease has a negative impact on social life.It is worth emphasizing that the quality of life depends on adaptive forces and the processes of coping with the disease, which may be justified by the results obtained by us.Implications for Practice: The issues addressed here, concerning the prevalence and importance of frailty and malnutrition in RA patients, represent a novel and under-researched topic in rheumatology. Therefore, further studies are warranted to understand whether improved nutritional status would be associated with improved cognitive function, reduced frailty, and better QoL. RA patients should be routinely screened for malnutrition and frailty, so that preventive measures can be implemented to reduce the risk of these conditions and minimize their QoL impact.Study Limitations: Our study is not free of limitations. The relatively small study sample may be considered one such limitation; it did, however, include a specific group of individuals aged 60 and above, diagnosed with rheumatoid arthritis. Moreover, frailty syndrome was only evaluated using a single self-reported instrument, though no consensus has yet been reached regarding the instrument to use in such evaluations. In addition, we only used a generic QoL questionnaire.In conclusion, malnourished RA patients had a significantly impaired QoL—more malnutrition was associated with poorer QoL. QoL included perceived health, social and physical domains. It was not, however, an independent determinant of lower QoL. Malnutrition was significantly associated with cognitive impairment and with frailty syndrome severity. Frailty was a strong and independent predictor of poorer QoL. Male sex and age was associated with better QoL in the environmental domain and Medication >3 was an independent predictor of better QoL in the physical domain.