Background: Electrogastrogram (EGG) can reflect gastric motility disorders in many diseases, but its application in acute pancreatitis (AP) has not been studied. Therefore, our study aimed to investigate the value of EGG in assessing the existence of gastric motility disorder in patients with AP and in predicting the severity of AP.Methods: Patients with AP admitted to the First Affiliated Hospital of Nanchang University from June 2020 to December 2020 were enrolled. Five EGG parameters , main frequency, average frequency, percentage of gastric tachycardia (PGT), percentage of gastric bradycardia (PGB)) were collected. The receiver operating characteristic (ROC) curve was constructed to judge the predictive value of EGG parameters to AP severity.Results: The PNGSW in AP patients was significantly lower than that of the control group (p < 0.05), and the PGB was higher in AP patients than that of the control group (p < 0.05). The area under curve (AUC) of the PNGSW and the PGB in diagnosing non-mild acute pancreatitis (N-MAP) were 0.777  and 0.775  respectively. After combining with C-reactive protein, the accuracy, sensitivity and specificity of predicting N-MAP were improved.Conclusion: EGG parameters can well reflect the gastric motility disorder of AP patients. The PNGSW and the PGB can be used to predict the occurrence of N-MAP. Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract and a rapidly developing inflammatory process of the pancreas . In recePatients with AP usually have gastrointestinal motility disorders . StudiesElectrogastrogram (EGG) is a non-invasive examination that monitors the electrical activity of gastric smooth muscle by placing electrodes at a specific surface position on the abdomen. Because of its non-invasive, painless, simple and objective characteristics, it has gradually become a new way to detect gastric motility in clinical practice . EGG canAccording to the Atlanta classification of acute pancreatitis revised in 2012 , PatientFive EGG parameters , main frequency, average frequency, percentage of gastric tachycardia (PGT), percentage of gastric bradycardia (PGB)) were collected in this study. EGG examination process: 1) Patient position: take the supine position, keep quiet and awake during the examination, avoid talking, calling and falling asleep; 2) Skin preparation: thoroughly clean the abdominal skin where the electrode is placed. If the body hair is too much, it needs to be shaved, and the conductive paste is applied to reduce the skin impedance. Place the electrode as shown in Refer to the published research and the Dutch MMS gastrointestinal motility examination system used in this study , The defIn addition, the following information was also collected: 1) Demographic characteristics, including age, gender, AP etiology, smoking and drinking history, hypertension, etc.,; 2) Laboratory examination and severity score (collected within 24 h of admission), including serum albumin level, C-reactive protein level (CRP), procalcitonin level, D-dimer level, urea nitrogen level, blood glucose level, calcium level, interleukin 6 (IL-6), interleukin 1β (IL-1β), acute physiology and chronic health evaluation (APACHE) II score, bedside index for severity in AP (BISAP score), modified CT severity index score (mCTSI score) and systemic inflammatory response syndrome (SIRS score); 3) Clinical outcomes included length of hospital stay and total cost of hospitalization.t-test or variance analysis. The measurement data of non-normal distribution were expressed as median (interquartile range), using non-parametric test. Count data were expressed as frequency (percentage), using chi-square test or Fisher exact test. The receiver operating characteristic curve (ROC curve) was constructed, and the predictive value of EGG parameters on the severity of AP was evaluated by calculating the area under the ROC curve. p < 0.05 was considered statistically significant. Data were analyzed using SPSS software (v26.0).The measurement data of normal distribution were expressed as mean ± standard deviation, using p < 0.05), while the PGB was significantly higher than that in the control group (p < 0.05). However, there were no significant differences in the mean frequency, the main frequency and the percentage of gastric tachycardia between the two groups (p > 0.05), which may be related to the majority of mild patients in the case group.A total of 83 AP patients were included in this study. According to the Atlanta classification criteria, there were 41 patients with MAP, 36 patients with MSAP, and 6 patients with SAP. The average age was 46.55 ± 13.36 years old, including 57 males (69.4%). The main causes of AP were gallstones (33.7%), hypertriglyceridemia (37.3%), alcohol consumption (4.8%), post-ERCP (2.4%) and mixed (9.6%). Another 10 cases (12.0%) were diagnosed as idiopathic AP due to unknown etiology. Most studies have shown that AP patients have gastrointestinal motility disorders. In order to objectively demonstrate this fact, 12 healthy normal people were selected as the control group, and EGG examination was performed on them and AP patients. As shown in p < 0.05), while the main frequency and the PGT were not significantly different among the groups (p < 0.05), while the average frequency was not significantly different between any two groups  and 0.775 , respectively. The cutoff values of N-MAP PNGSW and PGB calculated by Youden index were 72.21%  and 27.89% , respectively. In general, the accuracy of PNGSW and PGB in predicting N-MAP was similar, but the specificity of PGB was higher. Then the ROC curve was constructed with the combination of PNGSW + CRP and PGB + CRP  and non-mild acute pancreatitis group . ROC curve was constructed, and the value of each index in predicting N-MAP was evaluated by calculating the area under the ROC curve (AUC) ; Table 3GB + CRP ; Table 3EGG is an examination that monitors the myoelectric activity of gastric smooth muscle by placing electrodes in the abdomen. When it is correctly recorded, EGG-related parameters can reflect gastric motility. Normal gastric myoelectric activity includes slow wave and spike . Slow wave determines the maximum frequency and propagation direction of gastric contraction. When gastric slow wave is accompanied by spike, gastric contraction occurs. It is worth noting that not every gastric contraction is accompanied by spike . StudiesTo the best of our knowledge, this observational, cohort study is the first to link EGG and AP. Through strict and standardized EGG examination of healthy normal people and AP patients, and based on fast Fourier transform spectrum analysis, it was found that the percentage of normal gastric slow wave in AP patients was significantly lower than that in control group, while the percentage of bradygastria was significantly higher than that in control group, which objectively proved the existence of gastric motility disorder in AP patients. It may be because the sample size included in this study is small, and the proportion of mild symptoms in AP patients is relatively high, so there is no statistical difference in the main frequency and average frequency. On this basis, AP patients were divided into MAP, MSAP and SAP groups. It was found that there were significant differences in inflammatory factors CRP, PCT and various AP severity scoring systems among the three groups. Similarly, EGG-related parameters, such as mean frequency, percentage of normal gastric slow waves, and percentage of bradygastria, were also statistically significant in AP with different severity. Unfortunately, we found that there were significant differences in the percentage of normal gastric slow waves and the percentage of bradycardia between MAP and MSAP, MAP and SAP, but there was no significant difference in the average frequency between any two groups.Therefore, the patients were further divided into MAP and N-MAP groups. By constructing the ROC curve, it was found that some parameters of EGG, the percentage of normal gastric slow wave  and the percentage of bradygastria  could be used to predict the occurrence of N-MAP, with a sensitivity of 78.6%, slightly higher than that of CRP (73.8%). The combination of EGG parameters and CRP showed that the diagnostic performance was improved. The percentage of bradycardia combined with CRP to predict N-MAP could improve the sensitivity and maintain high specificity. In this study, the sensitivity of CRP to predict the occurrence of N-MAP was only 73.8%, which was much lower than 88% of Sternby et al. , This maThere are still some limitations in this study, Firstly, the sample size of this study is too small, especially SAP; Secondly, this study did not prove that there was a statistical difference in EGG parameters between MSAP and SAP, which may be related to the small sample size; Thirdly, because AP is in the early stage of fasting, the examination in this study belongs to the improved EGG, and EGG parameters of at least 30 min are recorded only in the fasting state. Therefore, there is no statistical analysis of the main power, and the postprandial/preprandial power ratio cannot be calculated. However, we believe that this has little effect on the results of the study, because the absolute value of the main power of EGG has no physiological and clinical significance . FourthlIn conclusion, this study proves that EGG is a new, non-invasive and simple method in AP, objective examination of gastric motility can be applied to AP patients in the early stage of clinical practice to predict the occurrence of N-MAP, which is conducive to timely intervention to prevent the aggravation of AP. However, the results of this study still need to be further verified by a large number of multi-center, large sample size prospective studies, and dynamically observe the changes of EGG parameters during the course of disease.


A total of 189 students were recruited, with 92 in the intervention group and 97 in the control group. The research assistant was responsible for student recruitment through email invitations and allocating the students into the control group or the intervention group. A Wilcoxon analysis was performed and revealed significant differences in PS and CR between the two groups (p < 0.001). The analytic results showed that the PSI, particularly in domains of Problem-Solving Confidence (PSC) (p < 0.001) and overall PS (p < 0.001), and the CR (p < 0.001) had significant improvement after HFPS, particularly in the intervention group. The study concluded that the structured HFPS guideline significantly improved the students’ problem-solving and clinical reasoning abilities. Nurse educators play an important role in providing explicit learning instructions in a simulation guideline that directs and guides students to learn at each stage of HFPS. The students can be directed to be engaged in their learning through HFPS to enhance their competence in knowledge and skill development (PS and CR) for their personal and professional development.High-fidelity patient simulation (HFPS) is widely used in professional training to enhance students’ competence in clinical management. A guideline for HFPS provides a systematic approach to direct students to learning during the simulation process. Problem-solving (PS) and clinical reasoning (CR) skills are essential to developing students’ professional competence in safe and effective care. These two skills should be initiated in the early training. A structured guideline was developed for HFPS. This study aimed to investigate the effects of the structured HFPS guideline on the development of PS and CR skills in junior nursing students. The students were required to go through four sessions, pre-briefing, simulation design, facilitation, and debriefing, for the HFPS; the study utilized the Problem-Solving Inventory (PSI) and the Nurses’ Clinical Reasoning Scale (NCRS) to measure PS and CR abilities before and after HFPS. Bivariate analysis, a one-sample  In today’s healthcare settings, technology has advanced and become more complex. As a result, healthcare services emphasize evidence-based practice ,2,3, andWith the increased complexity of healthcare services, nurses are expected to have greater accountability and independence to provide appropriate quality patient care . In currPS is the intellectual and analytic process that finds solutions to problems in specific contexts , while CHFPS is an advanced and innovative teaching–learning method that uses a computerised manikin in a simulated real-life scenario to allow students to integrate their knowledge and skills in their clinical decisions . HFPS haThis quasi-experimental study was conducted at a professional training institution.Students who (1) were in their first or second year of an undergraduate programme and (2) were aged ≥18 years were recruited. Those who (1) had been enrolled in another course with HFPS or (2) had a previous clinical placement were excluded to avoid contamination. Students in the 3-year and 5-year Programmes of the Bachelor of Health Science (Honours) in Nursing (BHSN) and the Higher Diploma in Nursing (HDN) were invited. The BHSN programmes were designed to train registered nurses, while the HDN programme caters to enrolled nurses.The sample size was calculated to reach a desired power of 0.95 and a type I error of 0.05, with an effect size of 0.5 using G*Power software (version 3.1.9.7). The required calculated minimum number of participants was 176 students. The eligible students were requested to join a group at their preferred timeslot. When the group size reached 8 to 10 students, the research assistant (RA) would inform the educator. The RA was not involved in the implementation of HFPS.The present study utilized a structured HFPS guideline, which was developed based on the Healthcare Simulation Standards of Best Practice (HSSOBP) by the International Nursing Association for Clinical Simulation and Learning [INACSL], drawing on clinical and academic expertise in HFPS . The guiThe PSI developed by Heppner and Petersen  is used The NCRS developed by Liou et al.  assessesThe recruitment of participants was conducted by the research assistant (RA) through email correspondence, wherein the purpose and details of the study were conveyed to prospective students. The RA was also responsible for the allocation of eligible participants into either the control or intervention group. The intervention group was instructed to utilize the structured HFPS guideline, while the control group followed the standard HFPS instruction. The HFPS was facilitated by two experienced researchers with more than five years of experience in teaching HFPS. To avoid contamination, the researchers acted as facilitators for the intervention and control groups, respectively, in separate venues. During the HFPS, the students were divided into three small groups, each with a 20 min role-playing session to provide care for the simulated patient. While one group performed in the simulation, the other two groups observed and provided feedback. Subsequently, debriefing was conducted for the purpose of performance improvement. The flow of data collection and study implementation is presented in Ethical approval (REC2021102) was sought from the Institutional Research Committee. Informed consent was obtained from the students after the study purpose and procedure were explained to them. All the data related to personal information were kept confidential.t-test was performed to compare the PS and CR abilities before and after the HFPS. All the statistical tests involved were two-sided, and p-values of <0.05 were considered statistically significant.Statistical analyses were performed using IBM SPSS version 26. Descriptive statistics were used for the demographic variables, including age, sex, study year, and study programme, and the outcomes of the intervention and control groups were presented separately. A paired A total of 189 students participated in this study without attrition. The mean age was 20.56 years (standard deviation = 3.14). p = 0.020; after intervention: γ = −0.50, p < 0.001). This indicated that PS and CR had a significant negative relationship. p = 0.027) and overall PSI score .There was a significant relationship between PS and CR abilities , overall PSI score (p < 0.001), and NCRS score (p < 0.001) between the two periods of HFPS. In the two periods of HFPS, the PSI score and NCRS score more significantly changed in the intervention group  than in the control group .In the paired samples t-test , there wt-test revealed that the effect sizes, as measured by Cohen’s d, were found to be less than 0.2 in both AAS and PC, suggesting a very small effect. Conversely, in the other PS subscales and NCRS, the effect sizes ranged from 0.3 to 0.7, indicating a small to medium effect.The paired p-value of less than 0.001 for PS, and a z-score of −5.92 with a p-value of less than 0.001 for CR.A Wilcoxon analysis was performed, due to the absence of a normal distribution. The findings indicate statistically significant variations in PS and CR measures between the two groups, as demonstrated by a z-score of −5.385 with a t-test (p = 0.016), PSC subscale score (p = 0.034), and overall PSI score (p = 0.012). Meanwhile, the NCRS score before the HFPS did not significantly differ between the two groups. However, there was no significant difference in all the PSI subscale scores and the NCRS scores between the two groups after the HFPS.In the independent sample t-test , there wt-test revealed that the effect sizes, as measured by Cohen’s d, were found to be less than 0.4 in all the subscales of PS and NCRS, indicating a very small to small effect.The independence p < 0.001), overall PSI score (p < 0.001), and NCRS score (p < 0.001) significantly improved. Notably, the HFPS significantly improves students’ PS confidence, leading to improved PS ability and increased CR ability. The HFPS provides a good learning and practice environment for students to apply their knowledge and skills to the simulated patient [p = 0.016), PSC subscale scores (p = 0.034), and overall PSI scores (p = 0.012). The control group exhibited more avoidance behaviours and lower confidence levels in PS compared to the intervention group. It is worth noting that pre-reading and orientation activities can enhance students’ confidence in PS, enabling them to effectively cope with problems and develop their clinical judgment abilities [This study revealed that the structured HFPS guideline effectively enhances the PS and CR abilities of junior students. Comparing the PS domains and CR between the two periods, the PSC subscale score ( patient ,12,23. S patient ,9. Therebilities ,9. Thus, p = 0.03, and ovebilities . FurtherSubstantial evidence shows that HFPS is a crucial component in enhancing clinical experience and clinical management skills ,31. A caDuring the role-playing session and the debriefing, the facilitator plays an important role in engaging students in learning through the HFPS more effectively ,31. The The structured HFPS guideline with adequate instruction, learning materials, and expected learning outcomes is essential to positively provide students with systematic direction and support so that the students achieve PS and CR development more effectively. This study successfully demonstrated the benefits of the structured HFPS guideline for student learning and skill development, including better preparation to increase knowledge acquisition and skill application, development of collaborative attributes, and enhancement of higher intellectual skills, such as PS and CR. Therefore, the structured guideline should be added to the courses with HFPS in the nursing curriculum. The results also promote the awareness of nurse educators to design HFPS guidelines and further enhance students’ PS and CR abilities, which are crucial for clinical judgement and decision-making, even in junior years. Therefore, early training cultivates PS and CR abilities in nursing students, enabling them to become familiar with decision-making and clinical management in the healthcare setting. It will produce a significant impact on the future clinical practice and nursing profession of the students.The structured guideline is useful to assist students in achieving their learning outcomes in a systematic manner. It is important to periodically review the content of the guideline to ensure that it meets the specific learning needs of students at different levels of education. Additionally, conducting studies to evaluate the effectiveness of HFPS in enhancing clinical practice would be highly beneficial in gaining a deeper understanding of students’ learning requirements and providing them with additional support to manage complex clinical situations.This study enables a direct comparison of the outcome measures between two stages of HFPS, providing reliable and accurate evidence of the intervention’s effects. Two educators with adequate experience in HFPS provide timely facilitation during HFPS. However, comprehending the development of students’ PS and CR necessitates a greater understanding of the sustainable impact of HFPS. In addition, the recruitment of students at a single professional training institution limits the generalisability of the results and the ability to draw causal inferences. To increase generalisability, a similar study should be conducted in multiple centres. The effectiveness of the intervention may be limited due to the lack of randomization, which can also introduce selection bias by creating systematic differences between the groups being compared.The structured guideline was developed to guide students to achieve their learning outcomes in a systematic way. The content of the guideline should be reviewed to meet the specific learning needs of students at various years. Studies to examine the application of HFPS beneficial to clinical practice are recommended to further understand students’ learning needs and provide more support for them to handle more complex clinical situations.The structured HFPS guideline in this study provides clear directions for students to prepare and enhance their knowledge and skills in clinical judgement and decision-making. Additionally, the HFPS guideline significantly improves PS and CR abilities before and after participating in HFPS. Throughout the learning process of HFPS, students not only apply their knowledge and skills but also increase their awareness and application of appropriate practice through a series of PS and CR. This study has significant implications for nursing education. As the use of HFPS continues to increase in professional training, including nursing, the findings highlight the importance of an HFPS guideline to improve student learning and competence in practising through HFPS, leading to better development of PS and CR abilities. Therefore, an HFPS guideline is crucial in enhancing students’ personal and professional development for more appropriate and safer clinical decisions and judgements.


After controlling for age and gender, greater nature connection significantly predicted lower depression and stress and improved well-being. Percentage of green space did not significantly predict any mental health outcomes. Further, time point (pre- or during COVID) and the interaction of time point with green space and nature connection did not significantly predict any of the outcome measures. The findings indicate that nature connection may play an important role in promoting mental health. Strategies to improve mental health and reduce mental illness should consider the role of nature connection and the use of interventions that involve direct interaction with natural environments.Background: Exposure to green space and feeling connected to the natural environment have independently been associated with improved mental health outcomes. During the coronavirus pandemic, people experienced restrictions on access to the outdoors, and health data indicated a decline in mental health in the UK general population. Methods: Data available from two independent surveys conducted prior to and during the pandemic enabled a naturally occurring comparison of mental health and its correlates prior to and during the pandemic. Results: Survey responses from 877 UK residents were included in the analyses. Independent  Mental health is defined as “a state of well-being in which every individual realises their own potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to her or his community” . By contEvidence suggests that the coronavirus pandemic resulted in further declines in mental health. Throughout the pandemic, mental health declined in the general UK population ,7, alongEvidence of the benefits of exposure to green space for mental health is growing . Green sNature connectedness, defined as the degree to which an individual feels connected to the natural world , is alsoThe impact of the pandemic on use of green space is unclear. In line with UK government coronavirus restrictions, after 23 March 2020, individuals could only leave their homes for the following reasons: (i) to shop for necessities, for example, food and medicine; (ii) for one form of exercise a day, alone or with household members; (iii) for any medical need or to provide care or to help a vulnerable person; and (iv) to travel for work purposes if the work could not be conducted from home. Whilst some studies reported increased use of green space during this time , other sTo date, the effect of the pandemic on the potential mental health benefits derived from nature connection and local green space has not been investigated. The aims of this study were therefore to: (i) examine changes in mental health outcomes from before to during the pandemic; (ii) confirm the relationship between percentage of local green space and nature connection with mental health outcomes; and (iii) explore whether the relationship between exposure to green space and nature connection with mental health outcomes differed before and during the coronavirus pandemic.Participants were recruited separately to take part in two independent online surveys, both of which included questions about nature connection and mental health. Studies were advertised via social media, including Facebook and Twitter, using a snowballing sampling strategy. Details of the studies were shared amongst the researchers’ social media groups and on institutional and research group websites. The researchers also shared details of the studies with their colleagues, collaborators, and contacts, all of whom were asked to share the survey with their networks. All participants were aged ≥18 years and residing in the UK at the time of survey completion.The two surveys were completed between 28 August 2019 and 2 June 2022, with study one taking place between 28 August 2019 and 30 April 2020 and study two taking place between 1 May and 2 June 2020. Study one was undertaken as part of a PhD study exploring the relationship between physical activity outside in nature and mental health and well-being outcomes. Study two was undertaken to explore changes in physical activity and well-being during the UK coronavirus lockdown. All participants that completed either survey on or after 23 March 2020 did so during the UK government’s coronavirus restrictions. For the purposes of the present analyses, participants completing a survey before 23 March were allocated to the pre-pandemic group and those completing a survey on or after 23 March were allocated to the during-pandemic group.All participants completed the surveys electronically via Qualtrics and provided their consent to take part in the study after reading the participant information sheet on the landing page of each survey. In both surveys, participants were asked to provide demographic information and to complete measures assessing their well-being, depression, anxiety and stress, and nature connection. Ethical approval was granted by the School of Health and Social Care and the School of Sport, Rehabilitation and Exercise Sciences Ethics subcommittees at the University of Essex (Ref: ETH2122-0071 & ETH1920-1283).The following measures were used for both datasets.Participants were asked to provide a range of demographic data, including age, gender, ethnicity, employment status, relationship status, and postcode.r = 0.954 [Participants’ well-being in the last month was assessed via the short form Warwick Edinburgh Mental Well-Being Scale (SWEMWBS) ,38. The  = 0.954 . In the  = 0.954 . During The Depression, Anxiety and Stress Scale 21 is a 21-item scale that is designed to measure the emotional states of depression, anxiety and stress . Each ofr = 0.67), which is frequently used in nature and green exercise research [The extent to which participants felt connected to the natural environment was assessed via the Nature Connection Index (NCI) . The NCIresearch . The mearesearch .Participant’s postcode data were used to identify their census area statistic ward (2001), which was subsequently used to determine the percentage of green space within each participant’s ward using the data of Richardson and Mitchell . This pen = 87.9%). SPSS (V.28) was used for analysis with significance set at a p value of less than 0.05. Since the data were derived from independent non-equivalent samples, preliminary analyses were conducted to compare the two samples. Independent t-tests were used to compare age, nature connection, and percentage green space, whilst a chi-squared test of independence compared the distribution of sex, ethnicity, employment, and relationship status in the two samples.Incomplete responses were removed from the datasets prior to analysis , independent Generalized linear modelling was conducted to explore multivariate predictors of depression, anxiety, stress, and well-being. For depression, anxiety, and stress, we used generalized linear models with Tweedie log-link function and employed robust estimates of covariance due to the skewness of the data and inclusion of zero responses. For well-being, we used a linear function and employed robust estimates of covariance. In Model 1, age and gender were entered as predictors to adjust for the effect of these demographic variables on outcome measures. Rather than testing the effect of multiple demographic variables in this study, we only included age and gender, as they have previously been reported to influence the green space–health relationship . In Moden = 470), whilst participants completing the study during the pandemic were from both study one and study two . An independent t-test revealed that the pre-pandemic sample were significantly older than the during-pandemic sample (t(873) = 7.87; p < 0.001), whilst a chi-squared test for independence revealed that there was a significantly smaller proportion of females in the pre-pandemic sample . A chi-squared test of independence also revealed significant differences between the pre-pandemic and during-pandemic sample in terms of employment status , with a greater percentage of the during COVID sample being in full-time employed. Overall, a majority of participants were of a white background and in full-time employment both before and during the pandemic  = 2.949; p = 0.003). There were no significant differences in nature connection scores between participants who completed the survey before and during the pandemic (p > 0.05). Nature connection scores were significantly higher than the reported normative values by Richardson et al. [t(469) = 7.209; p < 0.001) and during (t(406) = 7.037; p < 0.001) the pandemic and for the total sample (t(876) = 11.16; p < 0.001).Independent n et al.  for botht-tests revealed significant differences between participants who completed the survey before and during the pandemic for depression (t(875) = −4.061; p < 0.001), anxiety (t(817) = −4.528; p < 0.001), stress (t(875) = −6.126; p < 0.001) and well-being (t(875) = 2.896; p = 0.004). Participants who completed the survey during the pandemic had significantly worse scores on all well-being variables  = −6.403; p < 0.001) and during (t(406) = −10.319; p < 0.001) the pandemic. The pandemic mean was significantly higher (t(406) = 4.833; p < 0.001) than the mean pandemic score of 20.8 ± 5.1 reported by Smith et al. [t(469) = 4.537; p < 0.001) and during the pandemic (t(407) = 10.151; p < 0.001). Neither anxiety or stress scores pre-pandemic were significantly different (p > 0.05) from the normative values of 3.76 ± 5.90 and 9.46 ± 8.40, respectively. During the pandemic, both anxiety (t(405) = 5.606; p < 0.001) and stress (t(407) = 7.934; p < 0.001) were significantly higher than the normative values of Henry and Crawford [One-sample t et al.  both preAll models were significantly different from the intercept model, with Model 3 providing the optimal model fit for depression, anxiety, and stress according to AIC . Age wasp = 0.057) such that there was a stronger association of higher nature connection with lower depression pre-COVID compared to during the coronavirus pandemic.Age remained a significant predictor of depression, anxiety, and stress in models two and three; however, gender was no longer a significant predictor of anxiety or stress after including nature connection and ward percentage of green space in the model . Higher All models yielded a significant overall model effect, with Model 3 providing the best model fit . Age wasThe aims of this study were to: (i) examine changes in mental health outcomes from before to during the pandemic; (ii) confirm the relationship between percentage of local green space and nature connection with mental health outcomes; and (iii) explore whether the relationship between exposure to green space and nature connection with mental health outcomes differed before and during the coronavirus pandemic.t-tests revealed that pre-pandemic survey respondents had significantly higher well-being and lower depression, anxiety, and stress scores than survey respondents during the pandemic, with the pandemic mean for all variables being significantly worse than their respective normative values. However, the generalized linear modelling revealed that the survey time point did not significantly predict scores on any mental health outcome measures. Although evidence has consistently demonstrated the adverse impacts of the pandemic [In line with aim (i), independent pandemic ,8,9, it pandemic ,13. Our In relation to aim (ii), the findings revealed that after accounting for age and gender, greater nature connection was associated with significantly lower depression and stress, and improved well-being. This is in line with previous research that has demonstrated that nature connection is positively associated with well-being, increased happiness, more purposeful, fulfilling, and meaningful lives , a lower2 and did not take into consideration whether the green space was accessible, of high quality or use. Other studies looked specifically at access rather than exposure to green space. For example, Hubbard et al. [The percentage of green space in residential ward was not significantly associated with scores on any of the mental health outcomes after controlling for age and gender. Previous research has demonstrated that both exposure and access to green space is beneficial for mental health outcomes ,22,23,24d et al.  reportedd et al.  found pud et al. ,51, poteThe final aim of the study (iii) was to explore whether the relationship between exposure to green space and nature connection with mental health outcomes differed before and during the coronavirus pandemic. Although Model 3 represented the best fit for the data, the interaction of the study time point with green space exposure and nature connection was not a significant predictor of any of the outcome measures. This finding suggests that the relationships between green space exposure and nature connection with mental health outcomes were consistent across the two time points. For depression only, the interaction of time point and nature connection was approaching significance. The Wald chi-squared statistic indicated a stronger relationship between nature connection and depression pre-COVID compared to during the coronavirus pandemic. This finding could suggest that during the pandemic, there were other unmeasured variables that played a more important role in mental health, leading to a reduction in the importance of nature connection. For example, social interaction, which was restricted during the pandemic, might have had a greater effect on depression scores during this time.This study supports findings of previous research that indicated that nature connection is a significant component of the nature–health relationship. Nature-based interventions are already being used to support various populations, including people who have experienced trauma and people living with mental ill health ,53,54. TThe current study has a number of limitations that need consideration. Whilst the data were collected from a large sample of the general population, neither the overall dataset nor sub-samples are representative of the UK general population, with a majority of participants being female, white British, and in full-time employment. The percentage of accessible green space was lower in the ‘during’ group and may have contributed to the lower well-being scores reported by this group. Further, demographic variables not controlled for in the models, such as ethnicity and employment status, may have affected mental health outcomes. Nature connection scores were also significantly greater than the UK average in both samples. This therefore limits generalisation of the findings, and the exploration of how demographic factors relate to mental health outcomes. The data were also collected from two different sub-groups, as opposed to representing repeated measurements in the same sample over time. Whilst these repeated comparisons would have enabled further exploration of changes in mental health outcomes over the course of the pandemic, generalised linear modelling techniques were employed to robustly explore factors associated with mental health outcomes. To build on the data in the current study and to further explore whether the relationship between nature connection, green space and mental health outcomes differs as a result of the pandemic, it would be beneficial to collect data in comparative samples. These additional data would support comparisons of relationships pre-, during, and post-pandemic and further elucidate the longer-term influence of the coronavirus pandemic on these relationships.Overall, the findings of this study indicate that nature connection is significantly associated with decreased depression, anxiety, stress and increased well-being after accounting for the effects of age and gender. Whilst the pandemic resulted in worsened scores on all mental health variables, scores did not differ by study time point after accounting for age, gender and nature connection, further emphasising their importance. Strategies to improve mental health and reduce mental illness should consider the role of nature connection and the use of interventions that involve direct interaction with natural environments.


The Score for Moderate-to-Severe type of GO risk Prediction (SMSGOP) and the Score for Muscle-predominant type of GO risk Prediction (SMGOP) were constructed using the machine learning-based automatic clinical score generation algorithm. (3) Results: 55.3% were classified as mild type and 44.8% were classified as moderate-to-severe type. In the moderate-to-severe type group, 32.3% and 12.5% were classified as fat-predominant and muscle-predominant type, respectively. SMSGOP included age, central diplopia, thyroid stimulating immunoglobulin, modified NOSPECS classification, clinical activity score and ratio of the inferior rectus muscle cross-sectional area to total orbit in initial examination. SMGOP included age, central diplopia, amount of eye deviation, serum FT4 level and the interval between diagnosis of GD and GO in initial examination. Scores ≥46 and ≥49 had predictive value, respectively. (4) Conclusions: This is the first study to analyze factors in initial findings that can predict the severity of GO and to construct scores for risk prediction for Korean. We set the predictive scores using initial findings. The complex pathogenesis arising from the interaction of endogenous factors and environmental triggers, diversity, and ethnic differences in manifestations of Graves’ orbitopathy (GO) has made it difficult to tailor therapies for individual patients ,2,3,4. SThe epidemiological and clinical features for white patients with GO have been well illustrated, but there is a paucity of literature on GO in Asian populations. Li et al. investigated the characteristics of patients with moderate-to-severe GO in China . Asians In 2018, the European Group on Graves’ Orbitopathy (EUGOGO) identified four independent determinants as predictors of GO development in patients with newly diagnosed Graves’ disease (GD): clinical activity score (CAS), thyrotropin binding inhibiting immunoglobulin (TBII), current smoking, and longer duration of hyperthyroid symptoms . In addiAs some symptoms of GO are irreversible and can result in a pronounced loss of quality of life, the condition can be explained to the patient in advance with early commencement of active treatment ,17. In mTherefore, we classified the disease type according to the initial eye manifestations and the treatment they received at the time of final evaluation retrospectively and constructed a predictive score that can comprehensively predict the moderate-to-severe type of GO for Korean subjects. In addition, we attempted to identify factors at initial examination that were significantly different between patients requiring active treatment for diplopia related to the enlargement of extraocular muscles and those who did not, in the moderate-to-severe type group, and to construct a predictive score.We performed a retrospective cohort study of patients treated at the Department of Ophthalmology of Bundang CHA Medical Center, Republic of Korea. This study was approved by Bundang CHA Medical Center Institutional Review Board (IRB Number: 2021-07-054). All data were de-identified and the requirement for informed consent was waived due to the retrospective nature of the study. The study was performed in accordance with the tenets of the Declaration of Helsinki.Patients referred to the Department of Ophthalmology of Bundang CHA Medical Center for evaluation of GO between October 2002 and February 2021 were screened for inclusion in the study. The inclusion criteria were diagnosis of GO and follow-up at both endocrinology and ophthalmology clinics of our hospital for at least 6 months. Patients with an incomplete set of laboratory measurements, CT images, or other parameters for assessment of GO were excluded.The primary outcomes were determination of which initial ophthalmic findings were significantly different between types of GO. The disease type was classified at the time of final evaluation. Mild type was defined as the modified NOSPECS scores ≤ 5 and clinical symptoms necessitating only conservative treatment. If the mild type of clinical manifestation did not progress for at least 6 months, the severity of the disease was still considered as mild type. Moderate-to-severe type was defined as clinical symptoms requiring treatment other than conservative treatment at least once. These patients were divided into fat predominant and muscle predominant types. Fat predominant type was defined as presenting with clinical symptoms such as proptosis and lid retraction requiring active treatment, but no definite external ocular muscle (EOM) involvement. The most important factor is that these symptoms must be correlated with a definite increase in fat volume on CT. Muscle predominant type was defined as EOM involvement leading to diplopia within 30° of field of view on binocular single vision test (BSV test) and requiring treatment.The treatments for moderate-to-severe type include periorbital injection using triamcinolone acetonide, Botulinum neurotoxin type A (BoNT-A) and fillers, lid surgery, systemic corticosteroids, radiotherapy of the orbits, surgical orbital decompression, and strabismus surgery. For fat predominant type, periorbital injection , lid surgery, systemic corticosteroids and surgical orbital decompression were considered. In the acute phase, periorbital injection  was considered as an option for patients with severe eyelid abnormalities such as lid retraction and entropion that interfere with daily life. In the chronic phase, lid surgery was performed according to the type of symptoms. Systemic corticosteroids were primarily considered for patients with CAS 4 or higher and surgical orbital decompression was considered for patients with exophthalmos of 3 mm or more in the chronic phase. For muscle predominant type, systemic corticosteroids, radiotherapy of the orbits, BoNT-A injection to EOM and strabismus surgery were taken. First, radiotherapy was primarily considered for patients with diplopia and strabismus corresponding to muscle enlargement in the acute phase, but systemic corticosteroids were also selected according to the patient’s preference or general conditions. For chronic patients, BoNT-A injection to EOM or strabismus surgery was considered, depending on the degree of strabismus or diplopia.We developed scores, i.e., Score for Moderate-to-Severe type of Graves’ Orbitopathy risk Prediction (SMSGOP) and Score for Muscle predominant type of Graves’ Orbitopathy risk Prediction (SMGOP), to comprehensively predict the severity and type of GO, based on the secondary outcomes.Putative determinants for severity of GO were assessed at initial eye examination. They included age, sex, follow-up duration of GD and GO, interval between diagnosis of GD and GO, medical history , smoking behavior , history of GD treatment (radioactive iodine therapy (RAI) or thyroidectomy), CAS, the modified NOSPECS classification, proptosis by Hertel exophthalmometry , type and amount of eye deviation by HESS test, presence of central diplopia by BSV test, orbital computed tomography (CT) to measure cross-sectional area of each external ocular muscle except the inferior oblique muscle, orbital fat, and total orbit at 4 mm behind the eyeball. Each of external ocular muscle and orbital fat were calculated as a ratio to the total orbit. Biochemical severity of GD, i.e., thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels, and immunological severity, i.e., thyroid stimulating hormone receptor antibodies (TSH-R Ab), thyroglobulin antibody (TG Ab), thyroid peroxidase antibody (TPO Ab), and thyroid stimulating immunoglobulin (TSI), were also evaluated.TM  for TSI.We used variable immunoassay kits: Atellica IM Free Thyroxine , (RRID:AB_2895179) for free Thyroxine (FT4), Atellica IM Thyroid Stimulating Hormone 3-Ultra , (RRID:AB_2895183) for Thyroid Stimulating Hormone 3-Ultra(TSH3-UL), ARCHITECT Free T3 Reagent Kit , (RRID:AB_2885163) for Free T3, Elecsys Anti-TSHR_P , (RRID:AB_2801453) for TSH receptor Ab, Elecsys Anti-Tg_P , (RRID:AB_2894922) for Thyroglobulin Ab, Elecsys Anti-TPO , (RRID:AB_2631044) for Thyroid peroxidase Ab, ThyretainSome continuous variables were transformed into categorical variables for ease of interpretation and to deal with nonlinearity. Serum TSH, FT4, and FT3 levels were categorized into three groups: below the normal range, normal range, and above the normal range. TSH-R Ab, TG Ab, TPO, and TSI were categorized into two groups: negative and positive.t test and chi-square tests at the 5% significance level. The data were analyzed using R software, version 3.5.3 .In the descriptive summaries for the demographic table, categorical variables are shown as the frequency (percentage) and continuous variables are reported as the mean (standard deviation). Comparisons were performed with the We implemented the AutoScore framework (version 1.0.0), a machine learning-based automatic clinical score generation algorithm developed by Nan and Feng ,20. AutoAutoScore was used to select the most discriminative variables from all candidate variables. Parsimony plots  based on the validation set were used to determine the choice of variables. We conducted bootstrap variable selection to solve the problems of initialization and small data. We chose several variables that showed more than a certain level of improvement in performance. For defining “certain level of improvement”, we made 50 boot samplings. For each 50 Random Forest feature importance, we measured the improvement of AUROC as we added the variables one by one from most important variables list. If more than half was obtained (25 here) of improvement in AUROC after adding the variable, we selected those variables as final features. These selected variables highlighted the severity of GO on initial examination. The performance did not improve markedly when more variables were added to the scoring model. Predictive performances of the SMSGOP and SMGOP scores are reported based on the testing cohort with 95% confidence interval (CI), and validation of the score was visualized with binned scatter-plot and non-linear regression. The data were randomly split into two cohorts: a training cohort (80%) for development and a validation cohort (20%) for evaluation. A total of 633 patients referred to the Department of Ophthalmology of Bundang CHA Medical Center for evaluation of GO between October 2002 and February 2021 were assessed for eligibility. Among them, 221 did not complete the initial evaluation for GO, and 12 did not meet the follow-up criteria . FinallyOf the 400 patients included in the study, 221 (55.3%) were classified as having mild type disease and 179 (44.8%) as moderate-to-severe type disease requiring active treatment. Among the moderate-to-severe type subgroup, 129 (32.3%) were classified as fat predominant type and 50 (12.5%) as muscle predominant type. Their characteristics at initial examination are listed in We chose six variables as the parsimonious choice for severity of GO and they achieved a good balance in the parsimony plot, i.e., age, central diplopia, TSI, the modified NOSPECS classification, CAS, and ratio of cross-sectional area of inferior rectus muscle to total orbit. These variables highlighted the severity of GO on initial examination. Addition of more variables to the scoring model did not markedly improve the performance. We chose five variables as the parsimonious choice for muscle predominant type GO: age, central diplopia, amount of eye deviation, serum FT4 level, and interval between diagnosis of GD and GO. GO has unique characteristics in different ethnic groups, and its clinical presentations vary according to age, sex, smoking status, and other external factors . In thisLi Q et al. analyzed the clinical features of patients with moderate-to-severe GO in China and reported that the severity of GO was significantly associated with male sex, older age, smoking, family history of thyroid disease, and degree of proptosis . In addiThe classification of GO as mild or moderate has been carried out in most of the literature based on EUGOGO criteria. The classification based on EUGOGO criteria was for establishing treatment guidelines, and in our study, the disease type was decided by the severity, based on the modified NOSPECS score system at the time of final evaluation. In other words, patients were retrospectively classified according to the eye manifestations and the type of treatment they received. This classification helps predict the disease progression, related to severity and need of medical intervention based on the initial eye manifestations.We selected variables as predictors of moderate-to-severe type GO to construct a predictive score, i.e., age, central diplopia, TSI, the modified NOSPECS classification, CAS, and ratio of the cross-sectional area of inferior rectus muscle to the orbit. We used the autoscore term “risk” meaning, or equivalent to, “possibility” and the “risk” was quantified as a score. This predictive score (SMSGOP) has higher values than PREDIGO except for specificity  [At initial presentation, 385 patients showed the mild type and 15 patients showed the moderate to severe type of GO. Among initial ‘mild type’, 219 patients (56.9%) stayed as mild type, but 166 patients (43.1%) progressed to the moderate to severe type. Among initial ‘moderate to severe’, 13 patients (86.7%) stayed as moderate to severe type, but 2 patients (13.3%) turned to the mild type. So, 58% of patients would stay at the initial type of GO, but 42% of the patients progress to another type of GO, based on this SMSGOP model during the follow up period at least 6 months.In terms of each component of the predictive scores, the modified NOSPECS classification of 4 was associated with the highest corresponding risk (quantified as score). Higher CAS and modified NOSPECS classification tended to correspond to a higher predictive score. CAS <3 corresponded to a score of 0, while CAS > 3, indicating the active phase, was associated with the highest score. It should be noted that, the more severe and active GO was from the time of first evaluation, the more likely it was to develop into moderate-to-severe type GO. The score was the highest for age 51–64 years and second highest for age 28–51 years. The incidence of GD is known to show two age peaks in the fifth and seventh decades of life, with a mean age of about 43 years . This isRegensburg NI et al. divided GO patients into four groups—with no increases in orbital fat volume (FV) or extraocular muscle volume (MV) (25.3%); with only FV increase (5.3%); with only MV increase (61.1%); and with both FV and MV increases (8.4%)—and reported that increases in MV were present in the largest proportion . CompariAmount of eye deviation, age, central diplopia, serum FT4 level, and the interval between diagnosis of GD and GO are predictors of muscle predominant type of GO. SMGOP had higher predictive value than SMSGOP, except for lower sensitivity , and could be a very effective tool for evaluation generally.In terms of different components of predictive scores, amount of eye deviation <15° had a corresponding risk of 0, while >45° had the highest corresponding score of 43. If the EOM is severely affected leading to a large amount of eye deviation from the beginning of GO, this is a powerful indicator suggesting that the disease will progress to the muscle predominant type. Age ≥ 64 years was associated with the highest risk, with a score of 45. In older patients who have passed the acute phase, fibrotic changes can be assumed to occur in the extraocular muscles, causing irreversible changes and diplopia. The risk increased significantly from 0 to 38, with age > 32 years, so patients in this age group should be monitored carefully. The presence of central diplopia at initial examination was also associated with risk of muscle predominant type disease. When the interval between diagnosis of GD and GO was >10 years, the corresponding risk was 0. GO usually occurs within 2~3 years after GD diagnosis in most patients. However, it could also be interpreted that GO does not occur well in patients with GD prevalence period of more than 10 years, but even if it occurs, the probability of turning into the muscle predominant type is small. Some GD patients have been under anti-thyroid medication for more than 10 years, and they could happen to present GO manifestations at that time or later. Even though 10 years is not the usual time point for GD follow up, it was the meaningful cut-off time point in this study.In our study, we could obtain CT data for the GD patients with suspected thyroid ophthalmopathy, even with mild symptoms to evaluate the orbit. We presented six variables for moderate to severe type, so even if there is no CT data the other variables could help in predicting it. Five variables were applied for muscle predominant type, but they did not include CT data.This study may be flawed, because the inclusion criteria and study settings are not equivalent to other studies, since most patients for our study were referred by endocrinologists and general ophthalmologists, and their acute phase could have passed when they finally visited our clinic. This can be inferred by the CAS scores of the patients initially visited. The average CAS scores were 1.2, 2.4, and 3.0 in the mild type, fat predominant type, and muscle predominant type, respectively. It also had some limitations related to its retrospective nature and sample size. Machine learning classification has been proposed in GO previously . In thatIn conclusion, both SMSGOP and SMGOP are two models of artificial intelligence system for prediction of GO progression when doctors see Graves’ patients, based on the initial eye manifestations. These are very useful for doctors to explain the potential severity to patients and decide follow up and management plans on a regular basis. Therefore, we definitely recommend that doctors, not only ophthalmologists but also endocrinologists, apply the SMGOP model to pay attention to potential severity in GO patients and to treat these patients at the right time in the proper manner, which could avoid functional complications and disfigurement.


Studies evaluating breastfeeding promotion and support interventions suggest some economic benefits. This study assessed the direct and indirect costs of a multicomponent breastfeeding promotion and support intervention during the first two years of the infant’s life.p-value below 0.05.This is a cost-benefit analysis of data generated from a randomized controlled trial that aimed at investigating whether provision of a multicomponent breastfeeding promotion and support intervention to Lebanese mothers in the first six months postpartum would improve breastfeeding rates compared to standard obstetric and pediatric care. Data on 339 participants included information on maternal socio-demographics and health, infant nutrition and health, and direct and indirect costs of the intervention. The primary outcome was the benefit-cost ratio (BCR) of the intervention at one, six, 12, and 24 months. Secondary outcomes included the overall costs of infant nutrition and infant-mother dyad health costs during the first two years. Multiple linear regression models investigated the effect of the multicomponent intervention (independent variable) on the overall infant nutrition cost and the overall mother-infant health costs (as dependent variables), adjusting for monthly income and number of children (confounders) at different time points in the first two years. Similar regression models investigated the association between infant nutrition type  and infant nutrition costs and infant-mother health costs. Intention to treat analyses were conducted using SPSS (version 24). Statistical significance was set at a Exclusive/Predominant breastfeeding among participants declined from 51.6% in the first month to 6.6% at the end of second year. The multicomponent breastfeeding intervention incurred 485 USD more in costs than the control group during the first six months but was cost-efficient by the end of the first year , and by the end of the second year . In adjusted analyses, the intervention was significantly associated with fewer infant illness visits in the first year (p=0.045). Stratified analyses by the type of infant nutrition revealed that infants who were on Exclusive/Predominant, or Any Breastfeeding had significantly more favorable health outcomes at different time points during the first two years (p<0.05) compared to infants receiving Artificial Milk only, with health benefits being highest in the Exclusive/Predominant breastfeeding group. Moreover, Exclusive/Predominant and Any Breastfeeding had significantly lower costs of infant illness visits, hospitalizations, and infant medications during the two years (p<0.05), but had additional cost for maternal non-routine doctor visits due to breastfeeding . Whereas the overall cost (direct and indirect) during the first six months was significantly lower for the Exclusive/Predominant breastfeeding infants (p=0.001), they were similar in infants on Mixed Feeding or Artificial Milk.The prevalence of Breastfeeding is associated with significant economic and infant health benefits in the first two years. In the context of the current economic crisis in Lebanon, this study provides further evidence to policymakers on the need to invest in national breastfeeding promotion and support interventions. Breast milk is the ideal nutrition for preterm and term infants that ensures healthy growth and development of infants and young children . BreastfIn Lebanon, the prevalence of EBF is low, estimated at 58.3% in infants less than one month and 15% in infants below five months of age , 10. StuIn response to the low national breastfeeding rates and societal barriers to breastfeeding, we conducted a multicenter, two parallel-arm, single-blind multicomponent BF promotion and support trial that compared the effect of provision of a package consisting of prenatal BF education, professional lactation support and peer support for up to six months postpartum on six-month EBF rate of women in the community, in comparison to standard medical care. The multicomponent BF intervention resulted in a significantly higher EBF rate in the experimental group compared to the control group  . In thisThis is a cost-benefit analysis of data generated from a multi-center, two-arm, single-blind randomized controlled trial (RCT) that aimed to investigate whether the provision of a multi-component BF promotion and support intervention to mothers in the community during the first six months postpartum would improve BF rates, as compared to standard obstetric and pediatric care. The trial was conducted between December 6, 2013 and January 21, 2016. All participants provided written informed consent. The intervention consisted of three components: prenatal BF education, peer support, and professional lactation support. Details of the trial procedures and findings are described in the trial protocol . BrieflyParticipants were mothers who participated in the breastfeeding trial and completed at least one month of follow up (n=339). They were recruited from the antenatal clinics of two healthcare centers in Beirut, Lebanon. After obtaining written informed consent, participants were randomly assigned to an experimental group (n=160) and a control group (n=179). Inclusion criteria were healthy pregnant women who were in their first or second trimester of pregnancy and who planned to breastfeed after delivery. Women with any chronic medical condition, abnormal fetal screen, twin gestation, no intention to breastfeed, delivery prior to 37 weeks of gestation, were past the second trimester of pregnancy, or residing outside Lebanon were excluded , 21.Exclusive Breastfeeding, Predominant Breastfeeding, Mixed Feeding, Any Breastfeeding, Exclusive Formula Feeding (EFF), and Any Formula Feeding (Any FF).In this cost-benefit analysis study, we grouped the infants according to the type of milk they received for nutrition during the first six months of life. Nutrition group types were EBF was defined as feeding the infant human milk only without any additional food or drink, not even water [en water .Predominant Breastfeeding is feeding the infant human milk as the predominant source of nutrition, but allowing water, water-based drinks, or a maximum of two feedings of artificial milk in one week during the first six months.Mixed Feeding is feeding the infant both human milk and more than two feedings of artificial milk per week.Any BF is feeding the infant human milk with or without artificial milk.Any FF is feeding the infant artificial milk with or without human milk.EFF is feeding the infant artificial milk exclusively.Exclusive/Predominant Breastfeeding, Mixed Feeding, EFF, Any FF, or Any BF), number of artificial milk bottles per day, volume of artificial milk per bottle, brand of artificial milk formula, price of one can of formula, number of formula cans consumed per week, brand of water bottles used to prepare bottles of artificial milk, price of one water bottle, number of water bottles consumed per week, infant’s illness visit to a physician (Yes/No), number of infant illness visits, diagnosis of infant illness at each visit, cost of each illness visit, third party payment for illness visit (Yes/No), use of drugs for infant illness (Yes/No), cost of drugs per illness, infant hospitalization for an illness (Yes/No), number of infant hospitalizations, diagnosis of infant illness at each hospital admission, cost of each hospital admission, third party payment for infant hospital admission (Yes/No), and cost of drugs used during/after hospitalization.Data on the following variables were collected at months 1, 3, 6, 12, and 24 postpartum: 1) maternal variables: participant’s allocation , age, employment (Yes/No), number of living children, education, household monthly income, maternal non-routine doctor visit relating to BF (Yes/No), number of maternal non-routine doctor visits due to BF, cost of maternal non-routine doctor visits due to BF; 2) infant variables: type of infant nutrition  of the multicomponent BF intervention at one month, six months, 12 months, and 24 months. The BCR compares the discounted benefits of the intervention against its discounted implementation costs at each time point.Secondary outcomes included the differences between the experimental and control groups in terms of: 1) the overall cost of infant nutrition, 2) the overall health costs for infant and mother , during the following time periods: first month; months two to three; months four to six; first six months together; months 7 to12; first 12 months together (first year of infant’s life); months 13 to 24 (second year of infant’s life); and all 24 months together (first two years of infant’s life). Other secondary outcomes were the differences in the overall cost of infant nutrition and overall health costs of the infant-mother dyad at the same time periods stratified by the infant nutrition group type, irrespective of maternal allocation in the trial.We summarized continuous variables as means and standard deviations (SD) and ategorical variables as counts and proportions. To calculate the BCR, we first calculated the Net Present Value (NPV) of expenditures incurred by each participant in the trial . To calculate the NPV, all expenses were discounted using an annual discount rate (r) of 3%, which is appropriate for developing countries based on recommendations for economic analyses , 23. TheThe Discount Factor for any expense that happens Therefore, the formula of the BCR is as follows:A BCR greater than 1 indicates that the intervention of interest is efficient and saves money relative to the control. A ratio less than 1 indicates that the intervention is inefficient, and costs more than it saves relative to the control.EBF vs. Mixed Feeding vs. EFF groups using Chi-square and ANOVA for dichotomous and continuous variables, respectively.We conducted multiple linear regression analyses to compare the experimental and control groups with respect to the overall cost of infant nutrition, and the overall health costs for infant and mother, adjusting for any baseline characteristic that was significantly different between the two trial groups. These comparisons were done separately for month one, months two to three, months four to six, all first six months, months 7 to12, all first 12 months, months 13 to 24, and all 24 months. Moreover, we compared differences in infant illness visits and hospitalizations between the experimental and control groups as dichotomous (Yes/No) and continuous variables (frequency) using logistic and linear regressions, respectively. Similarly, we compared these two variables in EBF vs. Mixed Feeding vs. EFF using ANOVA; EBF vs. Any FF, and Any BF vs. EFF using the independent Student’s t-test. All statistical analyses were conducted as intention to treat analyses using SPSS (version 24). Statistical significance was evaluated at a p-value below 0.05.With respect to the comparisons of infant nutrition costs and health costs of the infant-mother dyads according to the infant nutrition group, we compared SD) age of 29.5 (4.9) years, with more than half  being employed, having a university-level education , with at least one child , and a monthly household income above 1,000 USD . A significantly higher proportion of women in the trial’s experimental group were primigravid (p<0.001) and had a higher monthly household income (p=0.003). Otherwise, the two groups had similar baseline characteristics , telephone charges and commuting of the support mothers , salaries of three research assistants , the cost of the BF video production , BF booklets and pamphlets , and the research assistants’ commuting cost . The implementation cost per participant was 43.60 USD in the first month, and 261.61 USD for each of the following time periods: 0 to 6 months (first six months of infant’s life), 0 to 12 months (first year of infant’s life), and 0 to 24 months (first two years of infant’s life).p=0.035), and a smaller number of doctor visits for infant illnesses during the first 12 months , as compared to the control group. However, in the adjusted intention to treat analyses, only the number of doctor visits for infant illnesses in the first 12 months remained statistically significant (p=0.045). No other significant differences were found between the experimental and the control groups at other time points with respect to infant and mother health outcomes, or to the cost of the following: infant nutrition, doctor visits for infant illnesses, infant hospitalizations, infant medications, maternal non-routine doctor visits due to BF, as well as overall total costs in both unadjusted and adjusted analyses (S1 Table).In the unadjusted intention to treat analyses, the experimental group had a significantly lower proportion of infants needing hospital admission during the period 7 to 12 months . Moreover, this group had fewer illness visits in the first three months, and fewer hospitalizations during the first year . The overall cost (direct and indirect) was significantly lower in the Exclusive/Predominant BF group during the first six months (p=0.001). As expected, the cost of water and formula in the Any FF group was significantly higher at all time points, whereas the costs related to infant health were significantly lower in the Exclusive/Predominant BF group such as illnesses visits in the first month (p=0.001), infant hospitalization during the first six months (p=0.016) and the second year (p<0.001), infant medications during the first month (p=0.017), months 2 and 3 (p=0.032), and second year (p<0.001). Cost of maternal non-routine doctor visits due to BF was significantly higher in the Exclusive/Predominant BF group only during months 4 to 6 (p=0.031). Details of the comparisons between the two groups are summarized in S2 Table.Infants who were on Any BF and EFF, Any BF was associated with a significantly lower proportion of infants who had illness visits  and hospitalizations  during the second and third months, and fewer hospitalizations during the first six months . Similarly, Any BF was significantly associated with fewer number of infant hospitalizations during second and third months (p=0.027), and during second year of the infant’s life (p<0.001). As for costs, EFF had significantly higher costs for water and formula at all time points. However, Any BF was associated with significantly lower costs of infant hospitalizations during the second and third months (p=0.038) and during the second year (p<0.001), as well as lower cost of infant medications during the second year (p<0.001). Any BF was associated with higher cost of maternal non-routine doctor visits due to BF during months 4 to 6 (p=0.047), in the first six months (p<0.001), and in the first year (p<0.001). However, the overall cost was not significantly different between the two groups at any time point. Further details of the comparisons between Any BF and EFF groups are shown in S3 Table.When comparing the groups of Exclusive/Predominant BF, Mixed Feeding, and EFF showed a significant difference in the proportion of infants who had illness visits in the first month being lowest in the Exclusive/Predominant BF group and highest in the EFF group . A similar trend was observed in the proportion of hospitalized infants  in the first month, and during the first six months , and in the number of infant illness visits in the first month (p=0.004), number of infant hospitalizations at one month (p=0.041) and during the first six months (p<0.001). Healthcare costs were lowest in the Exclusive/Predominant group and highest in the EFF, specifically in infant illness visits at one month (p<0.001), infant hospitalization during the first six months (p=0.001), and overall cost during the first six months (p<0.001). The cost of water and formula was highest in the EFF group and lowest in the Exclusive/Predominant BF group at all time points. Further details of the comparisons among the three groups are shown in S4 Table.The comparison of the three groups In this study, we conducted a cost-benefit analysis of a multicomponent BF promotion and support intervention composed of peer support, professional lactation support, and BF education. We found that although the intervention was not cost-efficient in the first six months postpartum, it was cost-efficient at years one and two. The net monetary benefits of the intervention were 2.44 times, and 2.82 times the costs of its implementation in year one and year two, respectively. There are few studies in the literature that evaluated the cost-effectiveness of breastfeeding promotion interventions that reported conflicting results. The differences in the cost-effectiveness of the breastfeeding interventions of these studies may be due to differences in their BF promotion interventions, study designs, durations of intervention delivery, and in the outcomes used to report cost-effectiveness.Chola et al.  assessedIn another study, Frick et al. conducted a cost-benefit analysis of a breastfeeding support intervention delivered by nurses and peer counselors (Breastfeeding Support Team) to low-income breastfeeding women in Baltimore, Maryland . The intOur intervention was also associated with a reduced number of infant hospitalizations and doctor illness visits during the first year of life. However, this was not paralleled with reductions in the costs of infant nutrition, infant illness visits, infant hospitalizations and medications, or maternal non-routine doctor visits due to BF at any time point. Moreover, the difference in the overall total costs between the experimental and the control groups was not statistically significant. This may be attributed to the fact that only 22.4% of the participants in the experimental arm complied with the three components of the intervention, which may have attenuated the association between the breastfeeding intervention and health-related costs . In addiExclusive/Predominant BF had less infant illness visits and hospitalizations, as well as less health-related costs and overall cost in the first six months of their lives. For example, in the first three months, we found a significant reduction in infant illness visits, hospitalizations, and medication cost. Similarly, there was a reduction in infant hospitalizations and medication cost between 12 and 24 months. However, Exclusive/Predominant BF was associated with an increase in the cost of maternal non-routine visits due to BF between the 3rd and the 6th months. This is an expected finding as BF women may experience BF-associated complications, such as mastitis, engorgement, or sore nipples necessitating medical care. Interestingly, infants on any BF also showed significant reductions in infant illness visits, hospitalizations, and associated costs at different time points in the first two years, and a similar increase in the cost of maternal non-routine doctor visits. These observed BF benefits in infants’ health outcomes and its associated cost savings are consistent with the literature. In a meta-analysis by Victora et al. [Our study also revealed that, irrespective of maternal allocation in the trial, infants who were on a et al. . Anothera et al. .Our findings are conservative in that we are missing many of the benefits of BF. The fact that our study stopped at two years means we only captured some of the benefits of BF. To the extent that the immunity acquired through BF continues to protect the child past age two years, we are unable to measure that benefit. Another limitation is that the benefits are measured in terms of physical health outcomes (absence of illness), whereas some of the benefits may be cognitive and behavioral. A further limitation is the fact that trial participants were recruited from two private hospitals in Beirut and were women who intended to BF. Therefore, our results may not be generalizable to women in rural areas or to women who did not intend to breastfeed. Moreover, only a small percentage of women complied with the three components of the intervention, which may attenuate the difference in the cost-benefit analysis between the two trial groups, especially that it was an intent-to treat analysis. We cannot exclude the potential for information bias since the costs of infant nutrition and healthcare utilization were self-reported and not based on invoices provided by the mothers. Finally, this study did not collect data on maternal food consumption, maternal health problems not related to BF, use and cost of breast milk pumps, and the cost of maternal absenteeism from work. The main strength of our study is its prospective design which reduces recall bias relating to the accuracy of data on infant nutrition and healthcare cost over the first two years of infant’s life. Also, we collected data on all infant non-routine health visits as well as maternal health care visits relating to BF-associated problems.Our multicomponent BF promotion and support intervention was associated with infant health benefits as well as economic benefits that were noted during the first two years postpartum. Moreover, exclusive, or partial BF was associated with significant infant-health and economic benefits in the first six months postpartum. Hence, our findings suggest that any intervention that increases the rate or duration of BF may be cost-beneficial. In the context of the current economic crisis in Lebanon, this study provides further evidence to policymakers on the need to invest in BF promotion and support interventions in Lebanon.


Metabolic syndrome (MetS) has the largest global burden of all noncommunicable diseases. Owing to the clinical heterogeneity of MetS, wide variations have been reported in the efficacy of moderate-to-vigorous physical activity (MVPA) and intermittent fasting (IF) for improving MetS. We searched five databases for randomized controlled trials published through December 2021, and 372 participants from 11 studies were included in this meta-analysis. Compared with MVPA alone, IF combined with MVPA had a more significant effect on improving body mass and levels of fasting blood glucose and high-density lipoprotein cholesterol; however, it was ineffective in improving triglycerides level, systolic blood pressure, and diastolic blood pressure. Subgroup analysis showed that, except for blood pressure, time-restricted fasting combined with MVPA had a better effect than alternate-day fasting with MVPA. Meanwhile, when the intervention lasted longer than 8 weeks, the effect of the combined intervention was significantly better than that of MVPA alone. This finding provides a basis for clinicians to manage the health of overweight individuals. This study also showed that Caucasians may be more suitable for the combined intervention than Asians. And the combined intervention may provide a preventive effect for MetS risk factors in healthy populations, although this may be due to the small sample size. In general, this study provides a novel perspective on special interventions for MetS traits. MetS isad libitum feeding (“feast days”)  engagement and calorie restriction (CR), are major contributors to reducing MetS risk factors , 9. PA et days”) .Although MVPA and/or IF have been reported to be beneficial for individuals with MetS risk factors in several studies, it remains unclear whether a combined intervention would have a better effect than a single intervention. In this study, by reviewing and meta-analyzing reliable results from previous studies, we evaluated and compared the benefits of MVPA combined with IF with a single intervention on the MetS risk factors. This study provides a novel perspective on specific effective intervention for the MetS risk factors.2.This study was conducted in accordance with the PRISMA 2020 guidelines . The PRI2.1.Five English databases  were searched from their inception dates  to December 31, 2021. The search terms included: “Exercise,” “Physical Activity,” “Aerobic Exercise,” “Endurance Training,” “Resistance Training,” “High-Intensity Interval Training,” “Intermittent Fasting,” “Time Restricted Feeding,” “Alternate-day Fasting,” “Metabolic Syndrome,” and “Metabolic Disease.” We also manually searched for published reviews and their references to identify other studies that met the criteria. Examples of search strategies for the three databases can be found in 2.2.Three authors  selected the eligible studies independently by reading the titles, abstracts, and full texts of the publications. The inclusion criteria were as follows: (1) randomized controlled trials (RCT); (2) studies published before December 2021; (3) the participants included healthy and obese adults, both male and female; (4) the methods included a description of the IF protocol and a PA program during the trial period; and (5) studies reporting the effect of IF combined with MVPA on the primary risk factors for MetS and the outcomes included body mass (BM), fasting blood glucose (FBG) levels, triglycerides (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, systolic blood pressure (SBP), and diastolic blood pressure (DBP).The exclusion criteria were as follows: (1) non-RCT studies; (2) non-human studies; (3) reviews, case studies, surveys, abstracts, conference papers, or repeated studies; (4) studies in elite or professional athletes; and (5) interventions that did not include IF alone or MVPA alone.2.3.Three authors  extracted the data by screening abstracts and full texts separately. The extracted information included the author, publication year, number of participants, baseline characteristics in the intervention and control groups, mean age, IF and MVPA intervention measures, outcomes, and study duration.2.4.Three authors  evaluated the quality of the included studies using the Cochrane Collaboration Risk of Bias (ROB2.0) to assess the risk of bias, as recommended . The Coc2.5.STATA ver. 16.0 was used to analyze the heterogeneity of the studies and calculate the n groups . Outcome3.3.1.In total, 432 records were selected according to the search strategy used in our study . After e3.2.All the included studies compared a combination of IF and MVPA intervention with a control group of IF or MVPA intervention alone. With a total sample size of 372 participants, 154 were in the combination group, 154 in the MVPA group, and 64 in the IF group. The average age of the participants ranged from 22.4 to 43.3 years. The types of MVPA included endurance training , aerobic3.3.The results of the Cochrane’s risk of bias assessment showed that the overall bias in most of the literature was low, whereas three studies raised some concerns and the bias in one study was high A. All stSupplementary Figure 13.4.p = 0.009]. This finding strongly suggested that the combination therapy was more suitable for obese patients with MetS (p = 0.110).Obesity is a high-risk factor for insulin resistance and T2D  and is aith MetS . Sensitiith MetS  revealedith MetS  was a soith MetS  and Eggeith MetS , which sp = 0.003). However, when the intervention time was less than 8 weeks, there was no significant difference between the two intervention approaches ; however, the difference was not significant in papers published in 2018 and before , whereas no significant difference was found between the “ADF + MVPA” and the MVPA groups (p = 0.012). However, BM changes in the two groups were not significantly different in Asia , whereas in the healthy population, the combined intervention showed a greater effect of changes on BM  and TRF  combined with MVPA intervention effectively reduced FBG levels than MVPA alone (p = 0.497), whereas in studies published in the last 3 years (after 2018), the combined intervention group was more effective for BM reduction  and in the Asian (Korean) study . Similarly, the combined intervention showed greater improvement in FBG in both obese  and healthy  population subgroups ; therefore, the random-effects model was adopted. No significant difference was found between the combined intervention and MVPA intervention groups .According to the heterogeneity test, there was significant heterogeneity among the six studies with TG (p = 0.037), whereas ADF combined with MVPA intervention did not  nor that based on study regions  were significantly different (p = 0.736), but the combined intervention showed more significant changes in TG levels in the healthy population , we found that TRF combined with MVPA significantly decreased TG levels than MVPA alone , a fixed-effects model was applied. Furthermore, a sensitivity analysis  was a favorable factor for HDL-C elevation compared with ADF combined with MVPA , whereas no better effect on improving HDL-C levels was observed in studies published before 2018 . However, studies in Asia (Korea) showed no significant difference in the HDL-C level , while in the healthy population, the combined intervention was more effective in improving HDL-C  and DBP (p > 0.05), a fixed-effects model was employed. The results showed a slight decreasing tendency in SBP  and a slight increasing tendency in DBP , However, these changes were not statistically significant (Blood pressure (BP), which is used to determine cardiac function and peripheral vascular resistance , is alsonificant .Moreover, there was no significant difference between the intervention and control groups in terms of changes in SBP and DBP in the original studies.3.8.Because IF alone could lead to nutritional deficiencies , few stu4.This study aimed to investigate effective approaches to improve the risk factors for MetS. In summary, our meta-analysis demonstrated the following four points: (a) Combining IF with MVPA was more effective than MVPA alone in improving BM, FBG, and HDL-C levels in adults, especially when MVPA was combined with TRF and the duration of the intervention was more than 8 weeks. Combined interventions may be more effective in preventing and managing MetS than MVPA alone; (b) The combined intervention did not show significant changes in the TG level and BP, although stronger effects were observed on the TG level in the TRF combined with MVPA subgroup; (c) More significant improvements in BM, FBG, and HDL-C levels were found in the subgroup of studies published from 2019 to 2021 (the last 3 years); (d) Compared with Asian studies, studies conducted in Europe and the Americas reported significant improvements in BM, FBG levels, and HDL-C levels by the combined intervention. (e) In the obese population, the combined intervention only had a more significant effect on FBG, while in the healthy population, the combined intervention showed more beneficial changes in BM, FBG, TG, and HDL-C. Overall, combining IF with MVPA was effective in reducing BM and FBG levels while significantly elevating HDL-C levels, suggesting that IF combined with MVPA may be better for preventing and treating individuals with these risk factors. In contrast, for patients with abnormal TG and BP levels, the combined intervention was not as effective, indicating that it may not be suitable for those with these risk factors.p = 0.000) but failed to significantly reduce TG levels simultaneously (p = 0.068). Although a decrease in TG implies a concomitant increase in HDL-C in general, our results, which did not show this trend, may be due to the potentially complex relationship between HDL-C and TG in patients with MetS, which is similar to that in patients with other diseases (In our main outcomes, IF combined with MVPA significantly increased HDL-C levels (diseases . To gaindiseases  or alterdiseases . Additiodiseases , 49. Thediseases .Studies on combined interventions have shown opposite results in different regions and populations. Combined interventions showed better results in studies conducted in Europe and the Americas, whereas no significant differences were found in studies conducted in Asia. Coincidentally, the subjects in the study conducted in Europe and the United States included healthy trained people, while the study conducted in Asia included obese people. The different subject types may be an important factor in this result. Similarly, subgroup analyses based on subject types showed that the combined intervention was more effective in the healthy population, whereas in the obese population, the combined intervention did not show a better effect than the single intervention. In the studies of the obese population, the single intervention already made a significant improvement on MetS risk factors , so the Subgroup analysis at the time of publication showed that the combined intervention significantly improved BM, FBG level, and HDL-C level than MVPA alone in the context of social development and dietary changes. Over the past decade, IF has emerged as a more effective alternative to traditional CR, potentially reducing body weight and is recommended for improving metabolic health , 50. MeaDue to limited number of involved studies, we only explored the influence of intervention duration on the effect on BM, and the results showed a more significant effect when the intervention lasted 8 weeks or more. This may be related to the long-term mechanism of IF and MVPA in MetS . Long-teWe found that subjects in all three studies with BP as an outcome indicator had normal baseline BP. Comparing to blank control, the combined intervention and the single intervention did not cause significant changes in BP , 31, 34.Furthermore, our study showed that the combined intervention was not more effective than IF alone in improving any metabolic risk factor. Interestingly, previous studies have reported that IF alone was more effective in reducing BM than a combined intervention . Thus, IThis study had several limitations. First, the sample size in this study was relatively small because of our strict inclusion criteria as well as the fact that there are currently few studies on combined interventions. Similarly, inadequate sample size leads to another substantial limitation, namely the heterogeneity of the study sample. Although we performed subgroup analyses of obese and healthy populations to reduce heterogeneity, there were still differences in body composition and physical activity at baseline in the included samples. The larger the sample size, the stronger the statistical power. More research data are expected to enhance the reliability of conclusions. Second, we compared the effects of the combined intervention with MVPA or IF alone, but our study lacked the comparison of effects between MVPA and IF. Future studies could consider using a network meta-analysis to compare the effects of these three interventions. Third, owing to the limitations of the original literature, BM was selected as an indicator for evaluating the effect of weight loss. In the future, more consideration should be given to body mass index and waist circumference to evaluate the effectiveness of interventions . Finally5.This study showed that different interventions had different effects on the various risk factors for MetS. Combined intervention with IF and MVPA, especially TRF combined with MVPA, was more beneficial than MVPA alone for individuals with increased FBG, TG, and HDL-C levels, and/or BM. However, the combined intervention had no significant effect on BP changes compared with IF or MVPA alone. Thus, different interventions may be appropriate for individuals with various risk factors. The identified combined interventions provide a new perspective on special effective interventions for MetS risk factors.HW contributed to the evaluation and interpretation of data, and the writing of the first drafts and the final version of this manuscript. YQ and BL contributed to the development of the review concept, assisted in the editing of all drafts of the manuscript, and critically reviewed the manuscript. YD contributed to the primary evaluation and interpretation of data, assisting in editing of all drafts of the manuscript and performed the statistical analysis. SH contributed to scrub data and maintaining research data for initial use and later re-use, and also performed much of the primary quality-of-evidence assessment. SR assisted in editing of all drafts of the manuscript and critically reviewed the manuscript. All authors contributed to the article and approved the submitted version.This research was funded by the Natural Science Foundation of Hunan Province in China, grant number: 2021JJ31070 and the Social Science Foundation Education Special Project of Hunan Province in 2021, grant number: 21YBJ24.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.