Physical activity (PA) is a non-pharmacological approach to alleviate symptom burden and improve health-related quality of life (HrQoL) in cancer patients (pts). Whether pts with myeloproliferative neoplasms (MPN) PA behavior changes due to symptom burden and/or knowledge of the putative beneficial effects of PA has not yet been investigated.We performed a large questionnaire study in MPN pts. Self-reported PA behavior and potential influencing factors of 634 MPN pts were analyzed. Questionnaires were used to assess demographics, anxiety, severity of symptoms, HrQoL, current level of everyday and sports activities, and the level of information regarding the importance/possibilities of PA. According to their PA, the pts were assigned to the three groups: “inactive”, “non-targeted active”, and “sporty active” and compared with each other.p ≤ 0.001) compared to the other groups. Inactive pts were significantly older and had a higher body mass index than sporty active pts. Inactive and non-targeted active pts felt less informed about the importance/possibilities of PA (p = 0.002).Key findings are that in 73% of the pts, the disease had an impact on PA, with 30% of pts reducing their PA. The prevalence of anxieties  regarding PA was 45%. Sporty active pts had a lower symptom burden and better HrQoL (Our results suggest that especially older and non-sporty MPN pts could benefit from motivational as well as disease-specific PA information. This study was registered at the German Registry of Clinical Trials, DRKS00023698. In addition to fatigue, the most common symptoms include concentration problems, bone pain, headache, dizziness, microcirculatory symptoms, itching, night sweet, depression, and anxiety –4. In adBased on the evidence regarding the effects of physical activity (PA) on functionality, symptom burden, and HrQoL in pts with solid tumors, acute leukemia, lymphomas, and myelomas , 12, it To support MPN pts in maintaining or implementing a physically active lifestyle in the long term, targeted information is warranted. The present study investigated which factors show an association with PA in MPN pts. The present study investigated (I) whether and how PA behavior changes due to a MPN disease, (II) whether anxiety of certain events such as thrombosis, bleeding, and skin reactions have an influence on PA, (III) how physically inactive MPN pts differ from active pts, and (IV) whether MPN pts have knowledge of the importance and possibilities of PA.2OnlineThe study was designed as a multicenter cross-sectional study. It was approved by the Ethics Committee of the University of Rostock (A2020-0274) and registered with the German Registry of Clinical Trials: DRKS00023698. Pts ≥ 18 years with any type of MPN  could paGeneral information. The following general characteristics were collected: gender, age, education level, family status, profession, height, and weight. The Body Mass Index (BMI) was calculated.Details of the disease. MPN subtype, year of diagnosis, disease-specific therapies  inhibitors, cytostatics , inteferon, and other therapies  were inquired.Physical activity. Questions asked for whether and how the PA had changed in everyday life and during sports since the diagnosis of the MPN, and whether they are afraid of certain events . Everyday activity was measured with the Godin-Shepard Leisure-Time Physical Activity Questionnaire (GSLTPAQ) and was classified into three categories: “insufficiently active”, “moderately active”, and “active”  ranging from 0 (very poor) to 100 (very good). Symptoms were assessed using single items of the MPN Symptom Assessment Form (MPN-SAF) (MPN-SAF) , supplemInformation level. It was recorded whether the pts felt sufficiently informed about the importance and possibilities of PA and the desire for more information.Pts were divided into three groups depending on their level of everyday (GSLTPAQ) and sports activities (SOC). Group 1 “inactive”: all insufficiently active pts who do no sports at all. Group 2 “non-target active”: all moderately and sufficiently active pts who do no sports at all. Group 3 “sporty active”: all moderately and sufficiently active pts who do sports regularly.2-test for categorical variables. All data were analyzed using SPSS . Statistical significance was assumed for p-values < 0.05.Continuous data are reported as means ± standard deviation, and categorical variables as counts and percentages. Mean differences for continuous variables were tested using Mann-Whitney U test and χ3In total, 766 questionnaires were received, of which 315 (41%) were in hard copy and 451 (59%) online. The response rate (handed out/received filled in) of the hard copy survey was 78%. Reasons for exclusion of questionnaires are presented in Further demographics and current therapies at the time of the survey are presented in The influence of a MPN disease on the PA of those affected is presented in p ≤ 0.001). Which events MPN pts are most afraid of during PA are presented in p = 0.038) and thrombosis (p ≤ 0.001). While CML pts had more anxiety about infections, ET and PV pts had more anxiety about thrombotic events compared to the other MPN subtypes. MF pts tended to have more anxiety about splenic rupture compared to the other MPN subtypes .Thirty percent of those who moved/exercised more consciously were more physically active. In contrast, 68% of those who were more careful were less physically active. Pts who reported moving less after diagnosis tended to have more anxiety about certain events than pts who reported moving as much or more  of the total cohort were categorized as insufficiently active, 109 (19%) as moderately active, and 361 (62%) as active. The analysis of SOC revealed that 203 (34%) pts were not action-oriented (stage of precontemplation), 98 (16%) and 41 (7%) were in the stages of contemplation and preparation, respectively. In total, 257 (43%) pts reported regular sports (stages of action and maintenance). The results for the different diagnoses are available in the All MPN pts who reported both GSLTPAQ and SOC (n = 559) were assigned to an activity group according to the information provided. For 18 (3%) pts, the information provided was not plausible. These were excluded from the subgroup analysis. The SOC as a relation to the GSLTPAQ scores are presented in p = 0.018; Group 3: 55 ± 13 years; p = 0.004), and had a higher BMI than the sporty active group . The sporty active group rated their HrQoL significantly higher than the other two groups . In addition, the sporty active group reported significantly less fatigue, bone and muscle pain, and concentration problems , compared to both groups. There were no differences in HrQoL and symptom burden between the inactive and non-targeted active pts.The demographics, HrQoL, symptoms, and side effects of the MPN pts, depending on the activity group, are presented in p = 0.070). Eight percent of the active pts intentionally lost weight.Inactive MPN pts tended to gain weight more often than the active ones . Falls during the last 12 months were reported significantly more often in this group, as well . Thirty-one percent of the sporty active group reported a splenomegaly, which was in the range to the inactive , but of note: in higher proportion compared to the non-targeted active .The inactive pts reported thromboses more often than the active pts . All pts, regardless of their activity level, expressed their wish to receive more information about PA.Two hundred and seventy-two (43%) of all participants stated that they did not feel sufficiently informed about the importance and possibilities of PA for their disease. The differences in the level of information depending on the activity group are presented in 4This is the first study to investigate the PA behavior of MPN pts and provide an overview of which factors show an association with PA in this population. The most important results are discussed below and information is derived for which pts may need to lead an active lifestyle for as long as possible.According to the presented data, the MPN disease and associated therapies had an impact on PA in 65-81% of the pts, depending on the MPN subtype. Approximately one in three pts reported a reduction in PA because of the disease, with the proportion highest in MF pts and lowest in ET pts. This is about as expected, as symptom burden varies according to diagnosis and consequently has different effects on HrQoL. Furthermore, the prevalence of moderate to severe fatigue, which is associated with a reduction in PA, is about 50% in MPN pts .Of importance is the result that in many MPN pts, depending on the MPN subtype, fear of certain events - especially infections, thromboses, bleeding, and skin reactions - had a negative influence on PA behavior. The reduction was not only limited to sports activities, but also affected everyday activities. Of particular interest is our finding that PV and ET pts more frequently reported anxieties compared to CML and MF pts in regards to the occurrence of thromboses. This might reflect the fact, that in PV and ET thromboembolism is often the initial disease complication that leads to the diagnosis. The rare occurrence of thrombosis in the present cohort (3%) suggests that the fear especially of PV and ET pts has to be addressed in order to avoid negative effects on PA. The high proportion of pts in the present study who regularly participate in sports despite anticoagulation and/or skin reaction suggests that these symptoms do not represent a limitation to sports activities. The numerous exercise interventions available for pts following high-dose chemotherapy and hematopoietic stem cell transplantation also suggests that exercise is safe for pts at increased risk of bleeding and infection, and that pts may benefit from numerous positive effects . It cannAccording to the presented data, 62% of MPN pts were sufficiently physically active in their daily lives at the time of the survey (self-reported), and 43% stated that they regularly played sports. These are unexpectedly high percentages and might be due to the survey design. Due to the voluntariness, it cannot be ruled out that more pts with an affinity for sports took part in the survey. In addition, 10% of the participants did not answer the questions on PA behavior or answered them inadequately and were excluded from the analysis. Furthermore, the cohort is quite young with an average age of 57 years and it is known that PA tends to decrease with age . LikewisAmong physically active pts, the proportion of pts with increased bleeding tendency or skin reactions is as high as among inactive pts. Consequently, these side effects/concomitants are not, or only to a limited extent, barriers to PA or sports. Mean comparisons showed comparable symptom burden and HrQoL for the inactive and non-targeted active pts. This suggests that a lack of motivation is the reason for inactivity rather than symptom burden. As behaviors tend to become entrenched over time, they are often difficult to change. To motivate previously inactive MPN pts to adopt an active lifestyle, a psychologist’s involvement may be beneficial. The most effective strategies to motivate cancer pts to be more physically active in the long term include motivational interviewing, coaching, and Bandura’s socio-cognitive learning (model learning) approach .In all groups, fatigue, bone and muscle pain, and concentration problems represented the most common severe symptoms. The reported prevalence and severity of these symptoms is comparable to results of other studies , 11. InaThe lower symptom burden and higher HrQoL of the sporty active pts in our study is consistent with the assumption of Eckert et al.  that tarThe presented data is based on a large cohort, but due to the survey design, there are inevitable limitations that should be taken into consideration when interpreting the data. First, due to the online format, no information is available on how many potential participants were informed about the study and declined to participate. Due to the high proportion of online questionnaires, a bias towards more women and “younger” respondents is suspected. Even though it is known that women often report a higher symptom burden, we suspect that the bias of the results due to the unbalanced participation of the genders is small . This as5In conclusion, it could be shown that the majority of MPN pts change their self-reported PA behavior due to the MPN disease or therapy. About one third of all MPN pts reduce the amount of PA, especially pts with PV and MF. In addition to fears, especially of infection, thrombosis and bleedings depending on the MPN subtype, higher age and motivation level also seem to influence PA. Sporty pts have a lower symptom burden and higher HrQoL than non-sporty pts. Physically inactive pts have a significantly higher prevalence of falls and higher BMI compared to physically active pts. Inactive and non-targeted active pts were significantly less likely to be informed about the importance and possibilities of PA. Our data clearly suggest that PA information and education, as well as sports programs, should be integrated into the treatment of MPN pts. Further studies, especially longitudinal studies are needed to verify the results of the survey study.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the University of Rostock. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.Conception and design: SF, CJ. Statistical analysis and interpretation: SF, JR, CJ. Data collection: PC, HA-A, SS, L-OM, JuG, JaG, VK-K. Writing the article: SF, JR, CJ. Critical revision of the article: SF, JR, PC, HA-A, SS, L-OM, JuG, JaG, VK-K, CJ. Obtained funding: SF. Overall responsibility: SF, CJ. All authors contributed to the article and approved the submitted version.


Objective: An individual’s articulation of pragmatic language development (PLD) signifies successful social interaction with others. Therefore, it is important to detect early pragmatic language impairment (PLI), whether as a primary disorder or as a symptom of other neurodevelopmental disorders. This study reports on validating the Arabic version of the Pragmatic Language Skills Inventory (A-PLSI). Methods: The PLSI was subjected to various validation stages before the A-PLSI was created. To assess PLD in preschoolers with and without psychiatric histories, 264 preschoolers were assessed in several cities in Saudi Arabia by their teachers and speech–language pathologists. Results: The results of this study included three key findings. First, the established psychometric features, including construct validity, criterion-related validity, and (confirmatory) factor analysis, all reported a high level of measurability to consider the A-PLSI a valid instrument for assessing PLD in school settings and diagnosing PLI in clinical settings. Second, the A-PLSI provided empirical evidence by identifying children with and without PLI, documenting their progress on pragmatic language ability, and distinguishing between preschool children in school and clinical settings. In addition, the A-PLSI approved the typical norm that the older the children, the higher their level of PLD: the data showed higher performance for children aged 6–7 compared to the lower PLD level of children aged 4–5. Conclusion: The present study contributes to the existing literature on PLD assessment in a school setting and PLI diagnosis in a clinical setting. More importantly, it adds a new validated tool to the few available instruments in Arabic to assess PLD and diagnose PLI in Arabian contexts. Pragmatics plays a major role in children’s development of language competencies and social communication . It is aSeveral studies have addressed the phenomenon of pragmatic development disabilities in preschool and primary school children and the relationship between social interaction and communication problems with pragmatic development problems. In contrast, children who use appropriate pragmatic communication skills usually have successful social interactions with their peers, family members, and teachers . In the Studies have shown that speech and language development disabilities are linked with challenging behaviours and social skills ,13. It hVarious assessment tools have emerged from testing the pragmatic development skills and the interactions of preschool children. For instance, the Language Use Inventory (LUI) is a parent-report measure, considering that parents and/or caregivers can perform this assessment since they interact with the child for a long time . FurtherOf relevance to this study is recent research which has shown that assessment and diagnosis play a vital role in ensuring typical language development for preschool children . BecauseThere is a lack of literature examining the development of pragmatic skills in Arabic literature. However, a few studies have attempted to explore some aspects of pragmatic skills development in preschool children and children in elementary school with impaired and normal abilities. For instance, in a study, the researchers compared the results of the Arabic Test of Pragmatic Language (TOPL-2)—as a psycholinguistic marker that measures the ability of individuals with Developmental Dysphasia (DD)—and the results of both the Pragmatics Profile (PP) and Observational Rating Scale ORS subtests from the Clinical Evaluation of Language Fundamentals (CELF-4) . In anotThe theoretical population of this study was preschoolers who speak the Arabic language as their mother tongue language, with and without a psychiatric history. The accessible population was preschoolers in Saudi Arabia with and without a psychiatric history. The sampling frame included preschoolers who were enrolled or not enrolled in preschools in Saudi Arabia. We defined preschoolers here as children who had not joined basic education, which could have been ≤7.0 years. The sample included 237 preschoolers without pragmatic language impairment and 27 with pragmatic language impairment. A detailed description of the population is provided in A total of 237 preschoolers between 4 and 7 years, both females and males, in different areas in Saudi Arabia were randomly selected for participation in the validation of the Arabic version of the PLSI. A detailed description of the participants is provided in A total of 27 Arabic-speaking Saudi children with various communication abilities were selected to assess the application of the A-PLSI at the Jeddah Institute for Speech and Hearing and Medical Rehabilitation (JISH), Jeddah, Saudi Arabia. JISH is a clinic that provides assessment and treatment for children and adults with various communication disorders. Amongst the participants, twenty children had different neurodevelopmental disorders; the remaining seven did not have any concomitant disorders. Informed consent was signed by all parents of children involved in this study. The Research Committee also approved the study at JISH. The PLSI is designed to assess children’s pragmatic language skills . TheoretThe PLSI is introduced in 45 items divided into three subscales: classroom interaction (CI), social interaction (SI), and personal interaction (PI). The use of the instrument includes: (1) identifying students who have PLI; (2) documenting progress in pragmatic language ability; (3) determining strengths and weaknesses in pragmatic language skills; and (4) data-collection for research .The translation process went through several stages before reaching the A-PLSI. Empirical evidence for the validation process is presented in detail in the results. We outline the main steps here. First, the instrument was translated using the literal translation by two academics holding doctoral degrees in translation and curriculum design. Back translation was conducted to ensure the accuracy of the content. The first draft was shared with three academics majoring in clinical linguistics, psycholinguistics, and speech–language pathology. Modifications and suggestions were provided for the further development of the translation, but none of these modifications were related to cultural differences. These suggestions are provided in All 45 items of the test were administered; however, some items were modified as they were not fully applicable in the clinical setting. These modifications included items that required reading or writing or were classroom specific. For example, Item 13, ‘writing a good story’, was modified into ‘telling a complete story’. The complete list of modifications is described in The English PLSI was normed on 1175 children between 5 and 12 in different areas of the United States. The data were collected between 2001 and 2004. The authors mentioned that they included additional data for children with disabilities. Coefficient alpha, test–retest, and interrater reliabilities were reported for this instrument. Content validity, item discrimination, and criterion-related validities were also reported. The validity also included construction validity and factor analysis. The three subscales and the pragmatic language index achieved acceptable values, confirming the measurability of the instrument for its sought purposes. We located only one attempt to validate the PLSI in the Turkish language . The parSince the purpose of the study was to validate the Arabic version of the PLSI, it was vital to compare data from children with and without a psychiatric history. All participants in the two groups were assigned randomly. Although the participants in the clinical group were selected to match the age requirement, no limitation for the type of disorder or even IQ level was considered.The data were collected between 19 October 2021 and 13 January 2022. Preschool teachers administered the instrument in the randomly selected schools in Saudi Arabia See . The admParticipants who met the criteria of this study were included regardless of the severity or type of communication disorder or the amount of time spent in therapy. Following the participants’ selection, the speech–language pathologist (SLP) administered the test and provided them with therapy. Pragmatics and social skills goals were always incorporated within any patient’s treatment plan. However, more goals targeting specific areas of weakness were included in the treatment plans for children who had affected social skills or were diagnosed with ASD. Various approaches were utilised to achieve those goals, such as social scripts, social stories, and social groups to generalise skills. Parents were also an integral part of therapy as all treatment plans were family-oriented. The parents were included in the therapy sessions to transfer learnt skills to the home environment.The data analysis went through several steps. First, all the data were moved from the booklets to Excel sheets. The Excel sheets were checked to ensure data accuracy. The Excel sheet was translated into English since the original one was made in Arabic. The data were then analysed using Minitab 18 and Jamovi 2.2.2. Both descriptive and inferential tools were used to analyse the collected data and achieve the study’s objective. The results are reported in detail in the following section.The objective of this study was to provide evidence of the validity of the A-PLSI. First, we present psychometric evidence for the validation of the instrument. This is explained in three sub-sections: normative information, validity, and the reliability of the A-PLSI. Second, we present empirical evidence demonstrating the instrument’s usability to assess PLD in a school setting and diagnose PLI in a clinical setting. This sub-section, which presents the characteristics of PLD in preschool children, is demonstrated in three parts: PLD and gender, PLD and pragmatic language skills , and PLD and age.The A-PLSI was normed on 264 children between the ages of 4.0 and 7.0 years residing in 15 cities in Saudi Arabia: Al Jubail, Al Khobar, Al-Kharj, AlNamas, Altaif, Eastern region, Hafar Al-Batin, Hail, Jeddah, Khamis Mushait, Makkah, Medina, Riyadh, Taif, and Yanbu.The data were collected between 2021 and 2022. Preschools and kindergartens within the aforementioned cities were randomly selected to participate in this study. Those who had special needs all resided in Jeddah. We focused on preschoolers during this study stage, but we plan to extend to children aged 5 to 12. The raters included preschool teachers and speech–language clinicians. A description of the representativeness of the normative sample is given below in For establishing the validity of the Arabic version of PLSI, we considered both face validity and content validity. Below, we describe the procedures we used to establish construct validity.Face Validity: To establish face validity, we followed two steps. In the first instance, the first author reviewed the translation and determined its relevance to the original. Secondly, the translation was sent to four experts in speech–language pathology, psycholinguistics, translation, and curriculum design. Based on feedback, the A-PLSI appeared to be suitable for evaluating PLD. A few items regarding translation and age-matching concerned the speech–language pathologist. First, Item 13 on the classroom interaction subscale (writing a good story) was considered unsuitable for preschoolers. This was discussed, and it was decided that advanced preschoolers could accomplish this, and it is typical of preschoolers to get involved in short storytelling. The second item was 20 in the social interaction subscale, where it was stated that taking turns in conversations was different from conversing. The proposed translation was used in place of the previous one. The other items are listed in Content Validity. This scale was designed to validate the validated scale in English, so we compared the validity of the content to the three subscales already included in the original version. The PLSI is composed of three main subscales: classroom interaction (Items 1–15), social interaction (Items 16–30) and personal interaction (Items 31–45). Teachers and speech–language pathologists who administered the scale confirmed that these three subscales were appropriate for measuring PLD in preschoolers.p = 0.001, r = 0.90, and p = 0.001, respectively. A high correlation score indicated that the A-PLSI correctly predicted PLD for preschoolers through CI, SI, and PI.Predictive Validity: PLD scores were correlated with preschoolers’ performance on CI, SI, and PI, assuming that A-PLSI would predict PLD level for preschoolers See . PLD andp < 0.05 level for the three dimensions: F  = 1.30, p = < 0.001; F  = 1.29, p = < 0.001; and F  = 1.29, p = < 0.001, respectively. This significance was also reported for the overall PLD and pragmatic language index: F  = 1.29, p = < 0.001 and F  = 1.29, p = < 0.001. Post hoc comparisons using the Games–Howell test indicated that the means between these two groups for all dimensions were statistically significant p = < 0.001  See . There wTo assess the data structure and further check the validity of the A-PLSI, we evaluated the correlations between the variables by factor analysis using Minitab 18 See . This waThese results show the unrotated factor loadings for all the factors using the maximum likelihood extraction method. This method was utilised because the scale had already been identified with the three factors used to measure PLD. The three factors had variances  that were greater than 1. The percentage of variability explained by factor 1 was 0.586. Factors 2 and 3 explained the percentage of variability of 0.044 and 0.026. In comparison, these results performed a varimax rotation on the data in the second part of the table to the right. Items 21–24  had large positive loadings on factor 1; this factor described classroom interaction and the potential for developing pragmatic language skills. Items 3–5  had large positive loadings on factor 2; this factor described social interaction and the potential for developing pragmatic language skills. Items 33–34 and 37  had large positive loadings on factor 3; this factor described personal interaction and the potential for developing pragmatic language skills. Together, all three factors explained 0.655 of the variation in the data.p < 0.001). Second, we checked the fit of measures where the CFI and TLI reported high values  with a low RMSEA (0.099) and a 95% CI . This also confirmed that the measure was fit to run this analysis. p-values were significant (p < 0.001) and had standard estimates (>40). More importantly, the factor covariances for the three subscales CI, SI and PI were all significant (p < 0.001) with high standard estimates . Finally, the path diagram , the SI subscale consisted of 15 items (α = 0.87), and the PI subscale consisted of 15 items (α = 0.94). Cronbach’s alphas for the 15 CI, 15 SI and 15 PI items was 0.93 See . These pWe also conducted reliability analyses for each subscale of the PLSI-A separately. The CI subscale consisted of 15 items (α = 0.97), the SI subscale consisted of 15 items (α = 0.97), and the PI subscale consisted of 15 items (α = 0.94) See .A one-way ANOVA was performed to determine if the proportion of PLD represented by CI, SI and PI differed by gender, PLS, or age.p < 0.033; SI: F  = 1.217, p < 0.008; and PI: F  = 1.227, p < 0.010. A post hoc comparison using Games–Howell was performed to verify this statistical significance, and the results indicated differences among preschoolers in the three dimensions of PLD according to gender. Generally, females showed higher PLD skills in CI, SI, and PI. There was also a main effect in the total performance of pragmatic language skills: F  = 1.224, p < 0.009. Females reported significantly higher scores than males  = 1.229, p-values were insignificant (p > 0.0). The significance of these differences was also tested using the post hoc comparison of Games–Howell. There was only significance for the standard score of SI p > 0.021. While the means of these conversions showed differences favouring males, these differences were statistically insignificant except for the SI. The reported differences for the raw scores were more valid, especially when looking at the pragmatic language index (M = 110) for females and (M = 111) for males.The analysis of the data revealed an issue regarding the influence of score conversion on participants’ overall performance based on gender. There was a difference conversion sheet provided for scores based on gender by the authors of the PLSI. For females, the conversion scores were lower when compared with males, who were given higher conversion scores when raw scores were converted to percentiles and standard scores. Females generally showed higher PLD scores than males, but this was completely reversed when converted scores were considered. Initially, all p < 0.001; SI: F (219) = 6.29, p < 0.001; and PI: F (376) = 6.31, p < 0.001. A post hoc comparison using Games–Howell was performed to verify this statistical significance, and the results indicated differences among preschoolers in the three dimensions of PLD according to the grade of pragmatic languages except for a few items. For instance, there was no significant difference between ‘below average’ and ‘poor’, ‘poor’ and ‘very poor’, or ‘superior’ and ‘very superior’ in the case of CI. This also applied to the case of SI and PI. In general, the highest means were reported for the ‘very superior’ grade showing a high level of PLD for preschoolers (see A main effect of gender was found for CI: F (417) = 6.29, p < 0.001; SI: F (16.90) = 3.64, p < 0.001; and PI: F (6.74) = 3.64, p < 0.001. A post hoc comparison using Games–Howell was performed to verify this statistical significance, and the results indicated differences among preschoolers in the three dimensions of PLD according to the participants’ age, except for a few items. For instance, there was no significant difference between ages 4 to 5, 5 to 6, and 6 to 7 in the case of CI and SI. More importantly, there was only reported significance for ages 4 to 6 and 4 to 7 in the case of the third dimension, that is, PI. In general, the highest means were reported for ages 6 and 7, showing a high level of PLD for preschoolers (see A main effect of age in years was found for CI: F (14.71) = 3.64, This study aimed to provide empirical evidence for the psychometric features of a validated version of the PLSI. This purpose was tested through the possible identification of preschool children with PLI, documenting the progress of pragmatic language ability, and comparing the characteristics of PLD between preschooler children with and without psychiatric histories. The results were presented in two sections. The first section presented the psychometric features for the A-PLSI, including normative information, validity, and reliability. The second included empirical evidence for the ability of the A-PLSI to measure PLD in preschoolers and identify differences among them considering age, gender, and pragmatic language skills. There are two key findings of the present research. First, the method showed acceptable psychometric features as an assessment instrument for measuring PLD in preschool children. The evidence showed that preschoolers without PLI outperformed those with PLI in CI, SI, PI, and overall PLD. Second, the A-PLSI could document pragmatic skills in preschooler children considering CI, SI, and PI and distinguish between children with and without PLI.The first key finding can be further extended into three findings. First, the A-PLSI is a representative, normed instrument. It was normed on 264 preschool children in Saudi Arabia distributed in different cities, including females and males and populations with and without a psychiatric history. Second, a high level of validity was established for the A-PLSI. This was achieved by considering both construct validity and criterion-related validity. The construct validity was achieved through face validity by different raters, and content validity by dividing the whole scale into three subscales—CI, SI, and PI—to measure PLD. Criterion-related validity was achieved through predictive validity, concurrent validity, factor analysis, and confirmatory factor analysis. All these reported a high level of validity, making A-PLSI a valid instrument with acceptable psychometric features that can assess PLD and diagnose preschooler children with and without PLI. Third, internal reliability was measured, and the results reported that the A-PLSI was highly reliable .The second finding can be extended into three findings. First, the A-PLSI reported controversial differences between females and males in PLD considering CI, SI and PI. When the results were calculated using the direct data, females reported higher PLD in CI, SI and PI. When the data were converted using the pragmatic language index provided by the authors of PLSI, males reported higher scores than females, albeit statistically insignificantly, except in SI. Second, the A-PLSI reported different levels of PLD for the participants according to three skills, namely, CI, SI and PI, with different grades including (very) superior, (above/below) average, and (very) poor. Third, the A-PLSI showed higher PLD for children with older age, that is, 6 and 7 years, compared to 4 and 5, who showed lower levels of PLD.This pattern of results is consistent with the previous literature reporting the need to validate or construct instruments for assessing PLD and the diagnosis of PLI in the Arabic language. Among the instruments validated were TOPL-2 and PP and ORS from CELF-4. The TOPL-2 is a formal assessment tool based on tasks to assess PLD in children with and without PLI. The PP and ORS are informal instruments used for the same purpose but filled in by parents of the children. They make a credible combination, allowing a triangular assessment of PLD and diagnosis of PLI ,38,39,40These data have some potential practical implications. For example, instruments for assessing PLD in Arabic are scarcely available, which might motivate other researchers interested in research in Arab countries to follow similar steps. Previous efforts have been made to validate or construct instruments. These include the validation of the Test of Pragmatic Language (TOPL-2), the Pragmatics Profile and Observational Rating Scale subtests from the Clinical Evaluation of Language Fundamentals (CELF-4) using modern standard Arabic ,41; LUI There are no accurate incidence reports  or prevalence  available but there are generally higher rates among children with developmental language disorders, particularly boys . Our finThere are at least two potential limitations concerning the results of this study. The first limitation concerns the number of included participants. While we intended to include a higher number of preschool children in both school and clinical settings, there was much hesitation from schools and clinics to allow accessibility due to the restrictions concerning COVID-19. A second potential limitation, also related to the pandemic, is that it was not possible to administer another test to compare the results of the A-PLSI.The findings of this study revealed that the A-PLSI is a valid instrument that can be used to identify children with and without PLI in Arabian contexts. The presented evidence illustrated that the established psychometric features for the A-PLSI could be reliably used to measure PLD concerning CI, SI, and PI to document the strengths and weaknesses of children in terms of pragmatic language ability. Furthermore, the presented evidence confirms that the A-PLSI could be used to measure typical PLD according to age, and it was shown that the performance of children increased according to their age. While these results are positive indicators that this instrument could be used by other researchers, it is vital to strengthen this method with other ones. The data could be collected twice by teachers, parents, and speech–language clinicians for validation. Another method is to use multiple instruments that could be formal, informal, or observational to reach a more concrete assessment, especially when used for diagnostic purposes in clinical settings or for the early identification of children vulnerable to atypical pragmatic language development.


Graphene nanoplates (GNPs)/TA15 composites were fabricated by pre-sintering and hot extrusion. During a room temperature tensile test, the dislocation was generated in grains. With increasing strain, the dislocation piled up along the interface between GNPs and Ti matrix, leading to stress concentration and microcracks. Then, the microcracks extended to GNPs or along the interface. The GNPs cracked under the shear force and the GNPs pulled out along with the crack propagation along the interface. This work provides a new sight in the room temperature tensile fracture behaviors. Graphene nanoplatelets (GNPs) have significant advantages on mechanical properties and specific surface area ,2,3 and Herein, the GNPs/TA15 composites were pre-sintered at 900 °C and hot extruded at 900 °C. A new method was introduced to investigate the room temperature fracture behaviors, combining SEM and EBSD. It is beneficial to reveal the fracture behaviors for optimizing the properties of GNPs/Ti composites. The GNPs/TA15 composites were fabricated by pre-dispersing, pre-sintering, and hot extrusion. The details are as follows: (I) Pre-dispersing: TA15 is a type of α titanium alloy with the advantages of mechanical properties and heat resistance, and its composition are shown in −3 S−1, using a universal testing machine (MTS) equipped with an extensometer.Scanning electron microscopy  was employed to observe the microstructure and side-fracture along ED, which was fitted with an EBSD system. The interface and phases were analyzed by transmission electron microscopy . Furthermore, the room temperature tensile tests were carried out at 10The microstructure, phases, and mechanical properties of GNPs/TA15 composites are exhibited in With respect to GNPs/TA15 composites, the TA15 was similarly prepared by pre-sintering and hot extrusion at the same parameters. The room temperature stress–strain curves of GNPs/TA15 composites and TA15 are presented in The SEM images were employed to deeply investigate the fracture process of GNPs/TA15 composites, i.e., observing the side morphology of tensile specimens with different locations, as shown in It is no doubt that the microcracks would form along the interface  and exteThe EBSD was adopted to analyze the microstructure evolution of GNPs/TA15 composites during a tensile test, i.e., KAM mappings with respect to different locations. The deformation of area IV was above the measured limiting of EBSD, resulting in an inaccurate value. Thus, area I, area II, and area III were deeply researched, as shown in The room temperature fracture behaviors of GNPs/TA15 composites were researched by combining SEM and EBSD. During the tensile test, a mass of dislocation generated in grains and moved to GNPs, because the deformation between the Ti matrix and GNPs was not consistent with each other. The dislocation moved and piled up, leading to stress concentration and microcracks. With the increasing of strain, the microcracks mainly extended to GNPs and were along the interface, forming cracked and pulled-out GNPs. In addition, stress transfer, dislocation strengthening, and solution strengthening allowed the ultimate tensile strength to improve from 977 MPa to 1273 MPa with the addition of 0.4 wt.% GNPs.


Caregivers were very satisfied with tailored program activities. Analyses of trends suggest non-significant increases in positive aspects of caregiving and decreases in caregiver burden and depressive symptoms. This is the first known study assessing the feasibility of the Savvy Caregiver Program for caregivers of LGBTQ+ individuals living with ADRD. Future research on the Savvy Caregiver Program for caregivers of LGBTQ+ people living with ADRD is needed.Nearly 350,000 lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) adults in the U.S. are currently living with Alzheimer’s disease and related dementias (ADRD). Informal caregivers face challenges impacting their ability to access and receive adequate and inclusive care for LGBTQ+ persons living with ADRD. The purpose of this study was to determine the feasibility and acceptability of the Savvy Caregiver Program for caregivers of LGBTQ+ individuals living with ADRD. Data for this secondary analysis come from caregivers ( Alzheimer’s disease and related dementias (ADRD) are some of the most common health concerns faced by adults over the age of 65. In the United States, about 6.5 million older adults are living with ADRD, with projections of 14 million by 2060 ,4.Research suggests that lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) caregivers experience greater loneliness, financial strain, and poorer health than non-LGBTQ+ caregivers ,6. As a There is currently limited research on the informal caregiving of LGBTQ+ older adults living with ADRD , and a dThe Savvy Caregiver Program is a widely used educational and behavioral program for caregivers of people living with ADRD ,16. The This secondary data analysis explored the feasibility and acceptability of a culturally adapted Savvy Caregiver Program designed to support caregivers of LGBTQ+ older adults living with ADRD . First, The Savvy Caregiver Program is comprised of six two-hour sessions. Each session focuses on different aspects of caregiving for individuals with ADRD. Session themes include, for example, general knowledge about ADRD, creating caregiving plans, and creating personal resources to support caregiving . SessionPrior to adapting and implementing the Savvy Caregiver Program for the LGBTQ+ community, a community-based organization’s staff had interviews with 10 current caregivers of LGBTQ+ people living with ADRD. The interview questions focused on caregivers’ backgrounds, relationships with their care recipients, challenges in caregiving, issues specific to the LGBTQ+ community , ability to meet caregiving needs, supports currently received, additional services needed, willingness to participate in caregiver support groups, description of the program and assessing program interest, and identification of barriers and facilitators to participation in the six-week Savvy Caregiver Program. One interesting finding that came out of the consultations was around language and a recommendation to consider using the term care partner rather than caregiver. It was suggested that the term, “care partner”, reflects a more egalitarian relationship between the person providing care and the care recipient, which could be important for addressing broader concerns related to stigma and assumptions about caregiving burden. Interviews also identified ways to recruit LGBTQ+ caregivers, including advertising to ADRD support groups, LGBTQ+ aging services and programs, and referrals from therapist and clinicians. Findings from the interviews with caregivers were also used to adapt some of the existing scenarios and role-playing activities that are part of the Savvy Caregiver Program curriculum. For example, a scenario was developed to represent how LGBTQ+ persons living with ADRD often live alone and LGBTQ+ caregivers may be non-relatives, friends or a neighbor. In this scenario, participants problem solved around keeping the person living alone with ADRD safe, engaged in activities , as well as supporting meal planning. Finally, given described limitations in access to respite care, LGBTQ+ caregivers recommended that the program provide space and respite services, such as a planned activity for persons living with ADRD at the same time as the Savvy Caregiver Program so that LGBTQ+ caregivers could attend the weekly sessions and not have to find alternative care support.To assess feasibility and acceptability of the adapted program, data was collected at the last session, after participants completed the 6-week program. Participants were asked to respond to seven questions (1 = strongly disagree to 5 = strongly agree) about satisfaction with and acceptability of the adapted Savvy Caregiver Program. These questions were used in a previous study and assessed satisfaction with program content, knowledge and skills gained, appropriateness of the training in increasing knowledge of ADRD and caregiving, personal confidence, feedback on the number of sessions for the program, and whether they would recommend the program to others .Demographic data included age, race/ethnicity, gender identity, sex assigned at birth, sexual orientation, level of educational attainment, income, and relationship to the care recipient. We utilized existing measures currently used to test the efficacy of the Savvy Caregiver Program ,19,20,21Caregivers were recruited through advertising by the local LGBTQIA+ community center and through case managers. A community-based event coordinator publicized the availability of the program through social media, newsletters, emails, and leaflets. Case managers recruited through caregiver support groups, current caregiver clients, and by reaching out to any LGBTQ+ clients’ living with ADRD who currently had a caregiver. To enroll in the program, participants emailed or called the program administrator to confirm their availability and ability to attend and complete the six-week program.n = 11). All tests were conducted using the alpha level of 0.05.Secondary analysis of data regarding feasibility and related quantitative data from pre- and post-intervention surveys were administered in-person by the program staff (K.P.) and entered into an online survey and data management program. Results are presented for both the matched  and the unmatched sample . The data were analyzed in R using non-parametric descriptive statistics, such as frequencies, mean and median scores. To look at potential feasibility and impact of the program on caregiver outcomes, we used Mann–Whitney tests and Wilcoxon signed-rank tests to assess differences before and after completion of the program for independent groups and matched pairs . Among participants, two-thirds identified as gay and one-third identified as straight. One participant identified as non-binary. More than half of the participants identified as White (56.3%), with Hispanic/Latino (25%), Asian/Asian-American (12.5%), and Black/African American (6.3%) making up the remainder. Two participants (13.3%) reported a positive HIV status with the rest of participants reporting negative or unknown status. Most participants (94.1%) were not currently working, with only one participant reporting they worked part-time. About 70% of participants reported they had more than a high school level education and 80% reported an income of $10,000 or less per year.For caregiving-related background, we examined the care partner’s relationship to the care recipient, the main reasons for providing care, and the length of time providing care. Regarding relationship type, half of respondents provided a write-in response. Nearly half of participants reported caring for non-relatives or friends, and over half reported caring for a spouse or partner (25%) or other relative (31%). Additional write-in responses included “not a care provider” and “neighbor.” When asked about the main reasons for providing care, 64.71% of participants reported ADRD, 35.29% general frailty, and 29.41% physical illness. Approximately half of participants provided care for more than one reason. Most participants (62.64%) had provided care for fewer than five years, while the remaining participants had provided care for ten or more years.n = 11). There was a small increase in the median response to the caregiver burden questions between the pre-  and post-intervention  survey responses. For depressive symptoms , there was a small decrease between the pre-intervention median of 1.63 (IQR = 1.13) and the post-intervention median of 1.50 (IQR = 0.75). However, there were increases in positive aspects of caregiving from pre-intervention  to post-intervention . For caregiver mastery, there was no change in overall scores from pre-intervention  to post-intervention score .Notable trends in outcomes after completing the intervention were found when comparing the pre- and post-intervention survey responses among the unmatched sample ; n = 11.n = 6), CES-D (n = 8), Caregiving Mastery (n = 9) and Positive Aspects of Caregiving (n = 7) scales. For both the Zarit Caregiver Burden Index and the CES-D, there was a slight decrease in median score. The median score on the Zarit Caregiver Burden Index at pre-intervention was 3.08 (IQR = 1.75) and 2.75 (IQR = 0.69) at post-intervention. The CES-D pre-intervention score was 2.00 (IQR = 1.63) and 1.50 (IQR = 0.38) at post-intervention. There was an increase in median score of the positive aspects of caregiving from 3.91 (IQR = 0.91) pre-intervention to 4.25 (IQR = 1.09) post-intervention. In terms of caregiver mastery, there was a slight decrease from pre-intervention  to post-intervention . Given the small sample size, we did not have power to exam statistical significance.The next analysis used a paired dataset of participants who completed both the pre- and post-intervention surveys . Sample At the conclusion of the Savvy Caregiver Program, participants were asked about their overall satisfaction with the program . Of the Findings from this feasibility study of the Savvy Caregiver Program for caregivers of LGBTQ+ persons living with ADRD suggest that LGBTQ+ populations would benefit from caregiver interventions and related strategies to support those caring for someone living with ADRD. The data collected from this study mirror findings from studies with larger sample sizes and diverse caregivers ,20,25. FWhile our study was underpowered to find significant differences in measures related to the efficacy of the intervention, we found modest improvements in several of the key measures used to assess the impact of the Savvy Caregiver Program. Pre- and post-intervention data suggest trends in reduction of caregiver burden and depressive symptom and improvements related to positive aspects of caregiving. A study testing the Savvy Caregiver Program for racial/ethnic minority caregivers  found similar results in terms of reducing depressive symptoms . This stParticipants reported high satisfaction with all aspects of the program. High satisfaction with Savvy Caregiver Program has been widely established, with several studies finding that caregivers rate the program as helpful ,26. A stThere are several areas that should be considered in future studies in terms of the feasibility of the Savvy Caregiver Program for caregivers of LGBTQ+ people living with ADRD. First, research has shown LGBTQ+ caregivers are more likely to live in separate households their care recipients . AdditioThere are several limitations of this feasibility study that should be considered. First, our small sample size and challenges related to both pre- and post-intervention survey completion limit the generalizability of our findings. Additionally, sample size was not predetermined to ensure power as we conducted a secondary data analysis of a community implemented program. However, the purpose of the study was to examine feasibility of the Savvy Caregiver Program and was not intended to determine efficacy or effectiveness. This study was a secondary data analysis, so some of the details on feasibility and reasons for non-response to pre- and post-intervention surveys could not be determined. For instance, more information on acceptability, such as the number of participants contacted to participate who did not end up enrolling, should be considered. A total of four participants or 24% did not complete the post-test at program completion and were lost to follow up. Thus, future research should consider the overall acceptance and dropout rates for the Savvy Caregiver Program. There is also the possibility for non-response bias among the individuals who only completed either the pre- or post-intervention surveys, and the potential that social desirability bias may have impacted scores on satisfaction with the program. Future randomized controlled studies testing Savvy with caregivers of LGBTQ+ people living with ADRD should be considered. Additionally, there were some unique demographic characteristics of our participants, with very few participants reporting current employment and most participants being over the age of 65. Employed caregivers might experience greater barriers in terms of attendance of the required sessions, as well as greater challenges in balancing caregiving demands. Research suggests LGBTQ+ caregivers tend to be younger than their heterosexual and cisgender counterparts . Thus, fThis work represents the first to examine the feasibility of the Savvy Caregiver Program for LGBTQ+ caregivers of people living with ADRD. There is a need for additional research to promote culturally relevant aging services and behavioral interventions for LGBTQ+ caregivers and their care recipients living with ADRD. For example, future studies examining the feasibility and efficacy of the Savvy Caregiver Program for LGBTQ+ caregivers should consider their diverse backgrounds including age, sexual orientation, gender identity, race/ethnicity, and employment status. This also includes exploring relationship types  between LGBTQ+ caregivers and people living with ADRD, and understanding the needs of LGBTQ+ caregivers in terms of knowledge, skills, and health outcomes. Finally, there is a need for additional programming and services addressing the unique health and psychosocial needs of LGBTQ+ caregivers and LGBTQ+ people living with ADRD.


Atypical Hemolytic Uremic Syndrome is a very rare condition that can be triggered in predisposed patients. It can remain undiagnosed and can result in a life-threatening event or permanent renal failure. We report a case of a 36-year-old pregnant woman who developed atypical hemolytic uremic syndrome postpartum. She underwent an emergency caesarean section due to abruptio placenta, and she developed biochemical alterations suggestive of a thrombotic microangiopathy. Due to worsening of renal function after plasma exchange therapy, we decided to start therapy with eculizumab. Therapy was carried out with a weekly dose of 900 mg IV for five weeks. An improvement of clinical and biochemical parameters was rapidly observed, and her renal function completely recovered. The therapy was continued for six months, with a dose of 1200 mg of eculizumab every two weeks. One year after discontinuation of the therapy, her blood pressure and renal function were still normal. Our case confirms that it is important to promptly identify a pregnancy-related thrombotic microangiopathy and that early therapy can be life-saving for the patient and can preserve renal function, avoiding dialysis. Thrombotic microangiopathies (TMAs) are conditions characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction, involving several districts, such as the brain, kidneys, eyes, heart, pancreas, liver, lungs, and skin. TMAs mainly include Hemolytic Uremic Syndromes (HUSs) and Thrombotic Thrombocytopenic Purpura (TTP) . These cWe report a case of postpartum aHUS, highlighting difficulties that health-care providers encountered in the diagnosis and management of this case.A 36-year-old pregnant woman, I gravida, was admitted to the Mother and Child Department of University Hospital of Naples Federico II, at 31 + 4 weeks of gestation. She did not have any chronic conditions; her singleton pregnancy was spontaneously conceived, and she referred to us that the pregnancy was uneventful until the time of admission. She presented abdominal pain and heavy vaginal bleeding. Clinical examination revealed a fixed contraction of the uterus, increased heart rate (105 bpm), and low blood pressure (100/60 mmHg); diarrhea and fever were absent.Combined blood tests presented alterations suggestive of TMA: thrombocytopenia , anemia (hemoglobin 8.1 gr/dL), and signs of hemolysis  and reticulocyte counts amplified. The haptoglobin consumption (undetectable [0.3–2.0 g/L]) and the presence of schistocytes in the blood smear confirmed the diagnosis.The direct Coombs test was negative, D-dimer was slightly elevated (1.5 mg/L [0.1–0.6]), and plasma coagulation tests were within normal range. Increased serum creatinine (sCr: 2.3 mg/dL [0.6–1.1]) and elevated liver enzymes (AST: 127 U/L [0–34]) were evidenced.Due to suspicions of an abruptio placenta, a prompt emergency caesarean section (CS) was performed, and the finding of a retro placental hematoma involving 2/3 of the placenta confirmed our suspicions. The newborn was born in cardiac arrest and was promptly reanimated by the neonatologist. The birth weight was 1350 g and the APGAR score was 0 at 1 min and 4 at 5 min.Soon after the CS, the patient underwent an eclamptic crisis , and therapy with magnesium sulphate was started. She was admitted to the intensive care unit. A CT scan was performed due to the persistence of neurological symptoms , and an intracerebral hemorrhage was detected, as seen in The day after, the patient referred to us a new onset of headache and visual disturbance; therefore, an MRI was performed, showing vasogenic cerebral edema, specifically in the axial T2-weighted images, suggestive of posterior reversible encephalopathy syndrome (PRES).A sudden worsening of thrombocytopenia and renal function was observed, and suspicions of pregnancy-related TMA were posed. ADAMTS-13 testing was not performed due to unavailability in our hospital, making it difficult to make the differential diagnosis between TTP and a-HUS. A single plasma exchange was carried out with fresh frozen plasma , corresponding to the patient’s circulating plasma volume, without improvement of the clinical and biochemical status. C3 and C4 were normal. Factor H antibody levels were not tested due to unavailability.Due to the worsening of renal function after plasma exchange, an empiric diagnosis of aHUS was made, and therapy with eculizumab (900 mg IV) was initiated four days after the CS. Therapy was carried out with a weekly dose of 900 mg IV for four weeks. Due to temporary unavailability, the patient received the anti-meningococcal A, B, C, W135, and Y vaccination before discharge only and was covered meanwhile by a six-week therapy with Ceftriaxone 2 gr daily until 14 days after the vaccination under strict clinical and laboratory monitoring.An improvement of clinical and biochemical conditions was suddenly observed .The patient was discharged after the fifth injection.At that time, her blood pressure was well controlled with methyldopa (500 mg twice a day), and the sCr and platelets count were normal . Proteinuria was 300 mg/24 h.The therapy was continued for six months with a dose of 1200 mg of eculizumab every two weeks.Genetic analysis  revealed that she had no pathogenic sequence variants identified.Three years after the discontinuation of the therapy, her blood pressure and renal function persisted normally.We reported a case of aHUS that developed in postpartum and was successfully treated with eculizumab.HUS is classically divided into typical (shiga-toxin mediated or STEC) HUS and aHUS. It is characterized by a dysregulation of the alternative complement pathway, which is responsible for complement-mediated endothelial damage, leading to TMA and organ injuries .Pregnancy is reported to be an important trigger of TMAs . The firMoreover, ADAMTS-13 testing could have been very helpful in our case in order to formally exclude TTP, but it was not available in our hospital at that time. Indeed, we could avoid the use of plasmapheresis that could be an invasive procedure leading to several complications . ADAMTS-It has been suggested that screening for complement dysregulation includes routine complement measures, genotyping, and autoantibody testing . In our The overlap in the clinical and biochemical manifestation of pregnancy-related aHUS and preeclampsia or HELLP syndrome has been reported in previous case reports that are summarized in In Secondly, we think that the good outcome of the reported case was related to the early therapeutic decision to use eculizumab. Eculizumab is a humanized IgG2/4 kappa anti-C5 antibody that acts by blocking the enzymatic cleavage of C5 to C5a and C5b. Its safety and efficacy as therapy for aHUS have been established in previous prospective studies , and it Thirdly, unfortunately, it is still uncertain how long the therapy should be prolonged with this antibody, and this is a challenge considering the high cost of eculizumab. We discontinued the therapy after six months, with the patient having normal renal function for more than three months, as suggested by Laurence , and ourFinally, it is important to provide information to the patient regarding the risk of relapse in a subsequent pregnancy. A large French series reported that, even if the risk is higher in the first pregnancy, it remains relatively high in subsequent pregnancies, and the patient should be aware of such a risk . HoweverEven if pregnancy-related TMAs are very rare events, it is important to train physicians to distinguish among different TMAs and to organize a multidisciplinary group including an obstetrician, nephrologist, hematologist, and anesthetist in order to optimize patients’ management.


Intraductal ultrasonography (IDUS) is a highly sensitive and non-invasive detective method that can be used to detect complete calculus clearance during endoscopic retrograde cholangiopancreatography (ERCP). In this study, we examined the preferable timing of IDUS during ERCP lithotomy.From 2017 to 2020, patients with choledocholithiasis were randomized into IDUS-BL (IDUS performed before lithotomy) group, IDUS-ALC (cholangiography and IDUS performed after lithotomy) group, and IDUS-AL group (IDUS performed after lithotomy) group. The influence of IDUS on the accuracy of prejudgment, the incidence of residual stones, the need for repeated lithotomy (RL), and fluoroscopy time were analyzed.P > 0.05). RL were performed in 5, 9, and 9 cases of IDUS-BL, IDUS-ALC, and IDUS-AL group, respectively (P > 0.05). IDUS-AL group had a shorter fluoroscopy time than the other two groups . Incidence of RL was related to the location of calculus [middle or lower part of common bile duct (CBD)], lithotripsy, dilated CBD , and inaccuracy prejudgment.A total of 184 patients were enrolled. No residual stones were found during follow-up in any of the three groups. There was no difference in prejudgment accuracy rate on size and number of stones between different groups (all IDUS performed after lithotomy is preferable for shorten fluoroscopy time during ERCP. IDUS is a reliable solution for the stone omission, which may be more valuable for patients with high-risk factors of RL. Common bile duct (CBD) stone, also known as choledocholithiasis, is a common clinical disease associated with abnormal metabolism, old age, impaired biliary function, and abnormal anatomical structure . CBD is Intraductal ultrasonography (IDUS) can provide real-time, high-quality cross-sectional images. IDUS has a higher diagnostic sensitivity for micro stones compared to computed tomography (CT), magnetic resonance imaging (MRI), and MRCP , as wellA total of 210 patients diagnosed with choledocholithiasis at Shanghai General Hospital between 2017 and 2020 were recruited. Inclusion criteria were: patients confirmed with single or multiple CBD stones. Exclusion criteria included intolerance of ERCP, post partial or total gastrectomy, inappropriate endoscopic lithotomy with a higher failure probability during evaluation, and accidental diagnosis of the tumor during ERCP. Finally, 184 cases were enrolled in our study. All patients were confirmed with single or multiple CBD stones by imaging method including abdominal ultrasonography (US), CT, and MRI. Written informed consent was obtained from each patient. The study protocol was approved by the Ethics Committees of the Shanghai General Hospital.All patients were prospectively randomized into three groups by generated random numbers: IDUS-BL group (IDUS performed before lithotomy), IDUS-ALC group (cholangiography and IDUS performed after lithotomy), and IDUS-AL group (IDUS performed after lithotomy). Patients in different groups underwent different stone extraction procedural. After successful cannulation, cholangiography was performed in all three groups of patients. Then, the IDUS-BL group underwent IDUS before lithotomy. Next, lithotomies were performed in all groups. After extraction of stones, patients in the IDUS-BL group underwent cholangiography; the IDUS-ALC group underwent cholangiography and IDUS, while the IDUS-AL group only underwent IDUS. If the operator considered incomplete clearance of CBD either by cholangiography or by IDUS, repeated lithotomy (RL) was carried out. The summary flow process is shown in Endoscopic retrograde cholangiopancreatography was performed using a standard side-viewing duodenoscope . A 2.0-mm-diameter IDUS probe with a frequency of 20-MHz  was advanced over a guidewire into the bile duct during the procedure. We used a BLF-600R X-ray machine  for fluoroscopy. All patients were under general anesthesia in the supine position.The duodenal scope was inserted into the second part of the duodenum. Cannulation of the bile duct was routinely performed. If cannulation time was longer than 15 min, an additional record was made. If the guidewire was inserted into the pancreatic duct, the performer either withdrew the guidewire or applied another guidewire by using the dual guidewire method, which was also reported in written. After successful cannulation, the catheter was advanced to the hilar area; then, cholangiography was done. In the IDUS-ALC group and IDUS-AL group, the amount, shape, and size of stones were defined according to the cholangiography results. In the IDUS-BL group, IDUS was done after cholangiography, and the amount, shape, and size of stones were recorded according to the cholangiography or/and IDUS results. The location of stones was defined according to different regions . Sphincterotomy was then carried out, and endoscopic papillary balloon dilation (EPBD) was determined according to the size of the stones. The application of lithotripsy, basket, or balloon was depended on the specific case. When the calculus was taken out, the actual size and amount of the stones were recorded. The number of stones was then graded: one and two stones were defined as score 1 and score 2, respectively; >2 stones were described as score 3. A score of sludge was defined according to the times of pulling out with basket or balloon as mentioned before. The size of the stone was measured according to the dimension of the instruments. After exaction of the stone, full clearance was confirmed by cholangiography or/and IDUS in different groups. Nasobiliary drainage was placed in all patients. The fluoroscopy time was also recorded after the operation.A routine blood test was carried out afterward. Possible complications were recorded, including hemorrhage, perforation, and acute pancreatitis. Nasobiliary cholangiography was performed within 72 h after the operation, and the abdominal US was performed within 1 week to see if there is residual of stones. Patients were followed up on 3, 6, and 12 months after discharge.t-test and the Mann–Whitney U test, and multiple comparisons were performed using the Kruskal–Wallis test and ANOVA with a Bonferroni correction using SPSS 13.0. P < 0.05 was considered to be statistically significant. Categorical variables were evaluated using Pearson χ2 test and Fisher exact test.Numerical data were expressed as mean ± SD. Continuous variables were compared using Student’s P > 0.05)  .P > 0.05). The diameter of CBD and the existence of diverticulum nearby the major papilla were compared, and no significant difference was found among the three groups .No significant difference in the location, max size, and scores of amount of calculus were observed among the three groups . No residual of the calculus was found in any of the groups during the follow-up period (The fluoroscopy time of the IDUS-AL group was significantly shorter than that of the IDUS-BL and IDUS-ALC group (p period .P > 0.05). Repeated lithotomies were done in 5, 9, and 9 cases of IDUS-BL, IDUS-ALC, and IDUS-AL group, respectively. No statistical difference was found in the frequency of RL and finding of RL  among the three groups , 85.5% (53/62), and 88.5% (54/61), respectively, while the accuracy of judging the number of stones in the three groups was 95.1% (58/61), 87.1% (54/62), and 83.6% (51/61), respectively. There was no significant difference among the three groups in the overestimation or underestimation of the size or amount of stones ; however, more stones were located in the middle or lower part of CBD in RL cases (P < 0.05). In addition, the lithotripsy ratio was higher in patients with RL (P < 0.05). The existence of the diverticulum was comparable in one-time lithotomy cases and RL cases. The diameter of RL cases was significantly larger than in one-time lithotomy cases (P < 0.05). RL cases had a significantly higher inaccuracy prejudgment ratio before lithotomy than others (P < 0.05)  .As a high-frequency and highly sensitive examination method, IDUS has important clinical value in diagnosing the biliary tract and pancreatic duct stenosis. Some studies suggested that IDUS is more accurate than EUS, transpapillary biopsy, and cell brushing for detecting biliary tract malignant lesions , 13. IDUIn this study, we applied IDUS before or after ERCP. IDUS performed before ERCP can provide additional information about the calculus. After lithotomy IDUS was applied as a double check method of complete clearance of stones. Our results showed that the fluoroscopy time of the IDUS-AL group was significantly lower compared to the IDUS-BL and IDUS-ALC groups due to the reduction of one post lithotomy fluoroscopy. However, the degree of complete stone clearance was not affected. IDUS before lithotomy can give a primary impression of the stones and is helpful for lithotomy. Yet, in this study, we found no significant difference in the accuracy rate for the estimation of stone size and number between the three groups. Therefore, whether IDUS should be applied as a routine examination before stone extraction needs to be further investigated. As a point of view, patients with high risk of stone residual should have IDUS confirmation.The quality of cholangiography can be influenced by the concentration of contrast and the unintended air in CBD. The personal experience of the operator may also affect the quality of the image. The infusion of contrast into hilar is a challenging process, which can affect the detection of stones. Detection of stones behind the endoscopic shaft or at the end of CBD also depends on the operator’s rich experience. Theoretically, IDUS can show the stones behind the shaft and at the end of the CBD more clearly than radiography, but the parapapillary diverticulum can also present as occupying lesion image under IDUS. Although it is difficult to fill the hilar with contrast, the contrast defect does not hinder the judgment of calculus. Our results also showed that in RL cases, the location of the stones was in the middle or lower part of CBD.Generally speaking, no residual stones were found during follow-up in the three groups, and no serious complications occurred. Compared with other researches, we achieved a lower complication rate, which can be partly attributed to the assistance of general anesthesia and proper indication for ERCP. The shorter average FT can be due to the personal experience of the operator. Moreover, RL during ERCP was not emphasized by other researchers. Our study showed that RL was related to the accuracy of stone prejudgment. Inaccurate prejudgment led to a higher RL rate. Also, both lithotripsy and bile duct diameter were relevant to RL. After lithotripsy, many stone fragments were produced, so it is difficult to judge whether all the stones were removed. Previous studies have suggested that biliary stenting after lithotripsy is safe, which is consistent with our experience . When thA few studies suggested that IDUS can reduce the residual rate of stones after ERCP. The residual stones missed by balloon occlusion cholangiography can be washed out with saline , 21. ThiThis study has a few limitations. (1) There was heterogeneity among total patients according to the exaction methods of stones. Differences in the application of basket and balloon might influence the operation time or FT. After RL, patients did not receive further confirmation of total clearance. (2) No control group  was selected. IDUS is a time-consuming procedure, although it affects the operation time, it does not rely on fluoroscopy, so it does not affect the fluoroscopy time. IDUS showed a high sensitivity for detecting calculus but was not very effective for quantitative analysis of the number of stones, which can be partially attributed to our score system. The grading system for stones was developed based on the difficulty of lithotomy and the length of operation time. Although it showed to be sufficient for the evaluation of stone clearance, it can cause misjudgment for IDUS.It was found that no matter IDUS was performed before stone removal for pre-judgment, or IDUS evaluation after stone removal, complete stone removal was completed without complications. After stone removal, IDUS can alone be used to confirm whether the stone is completely removed, reducing the radiation time. In summary, although prejudgment can simplify the process of lithotomy, the time and way of using IDUS need to be considered. Our data suggested that IDUS examination around lithotomy is helpful for the complete and safe extraction of stones. IDUS can also reduce fluoroscopy time and the rate of RL. Since IDUS can detect minimal stone in CBD, it can be potentially used as a golden standard for a total clearance of stones.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Shanghai First People’s Hospital. The patients/participants provided their written informed consent to participate in this study.HZ was responsible for the design of the subject and the revision of the article. ZJL was responsible for the collection and selection of cases and the writing of the article. Both authors contributed to the article and approved the submitted version.


The prevalence of excessive gestational weight gain (EGWG) during pregnancy is increasing, and it is extremely harmful to pregnant women and newborns. Previous studies have suggested that EGWG is associated with various factors. We conducted a systematic review and meta-analysis to identify, quantify and analyze determinants of EGWG and evaluate the effect of these determinants on EGWG.We searched for articles, from January 2009 to November 2020, related to the determinants of EGWG during pregnancy using four Chinese and four English databases. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was utilized to guide the systematic review and meta-analysis process.Seventy studies, which identified EGWG factors in pregnant women , were included and analyzed in the systematic review. A meta-analysis was conducted for 13 factors  and revealed that pre-pregnancy overweight (including obesity), younger age (≤ 30 years old), unemployed, primiparity, smoking, and being unmarried (including divorced) were risk factors for EGWG, while prepregnancy underweight and inadequate antenatal care were protective factors for EGWG. There was no significant correlation between EGWG and education level, alcohol consumption, planning pregnancy, food security, and whether access to nutrition guidance during pregnancy.EGWG was prevalent in pregnant women, and its prevalence seemed to be high and similar in many countries. Based on observational studies with medium-level and high-level evidence, some individual, family, and social factors were found to be associated with EGWG using qualitative and quantitative methods. In the future, exposure of pregnant women to risk factors for EGWG should be avoided, and interventions should be developed around the identified factors.The online version contains supplementary material available at 10.1186/s13690-022-00864-9. Excessive gestational weight gain (EGWG) is becoming a worldwide epidemic. Multiple studies conducted in different regions of the world have recorded the prevalence of EGWG in pregnant women. According to previous studies, more than half of pregnant women in the United States had EGWG . The EGWTo alleviate the increasingly serious problem among these special groups, the Institute of Medicine (IOM) revised its guidelines for weight gain during pregnancy in 2009. Compared to the guidelines proposed in 1990, the 2009 version focused more on healthy pregnancy outcomes, postpartum weight retention, and childhood obesity. According to IOM guidelines, the recommended weight gains for underweight, normal weight, overweight and obese women were 12.5–18, 11.5–16, 7.0–11.5, and 5.0–9.0 kg, respectively  AND [(risk factor*) OR (association factor*) OR (influencing factor*) OR (determinant*)]. The complete search strategy is provided in Additional File Two independent reviewers screened the studies according to the following inclusion criteria at the same time. Disagreements were resolved through discussion between the two reviewers and full group consensus. Otherwise, the references of the included studies were also tracked for more suitable studies. The inclusion criteria were as follows: (1) studies published between January 2009 and November 30, 2020; (2) the study was related to the determinants of EGWG in pregnant women, including individual, family, social and other factors. (3) the participants were singleton pregnant women with no primary pregnancy-related diseases before pregnancy; (4) the study was a cohort study, case–control study, or cross-sectional study; (5) The definition of EGWG followed the IOM guidelines revised in 2009. (6) for the research on the same sample , we selected paper with higher quality to be included; and (7) the study was published in Chinese or English.Two reviewers independently completed the quality assessment of the literature. Instances in which the two raters disagreed were reviewed by senior study personnel to determine the reported quality ratings.The Newcastle − Ottawa Scale (NOS) was used to evaluate the risk of bias in cohort studies and case–control studies from three aspects: study population selection (4 items), comparability between groups (1 item), and measurement of outcomes (3 items). The total score of the above items was 9 points. All eligible cross-sectional studies were examined using 11 items recommended by the Agency for Healthcare Research and Quality (AHRQ), including data source, sample representativeness, a detailed description of the object and research methods, and identification of confounding factors. The overall risk of bias was determined a priori and judged as follows: a score of 0 − 3 was considered low quality, 4 − 6 was medium quality and > 7 was high-quality .vs > 30] and education level [low vs. high]). (4) Data merge—two methods were used to obtain the OR value of the binary data merge. One was based on the original data, and the other combined the OR value of multiple categories using RevMan 5.3 software. For example, since age is multiclassification data, all categories (≤ 30 years old) were combined in one study at first. We then calculated the OR value of this determinant (≤ 30 years old) for EGWG. Lastly, the OR values were combined in all studies that mentioned this factor.Data extraction was conducted by two reviewers independently and discussed with the third senior study personnel if remained disagreement, followed four steps: (1) A standard template was designed for data extraction of study and sample characteristics, including general characteristics , research methods , determinants, and key findings. (2) Odds ratio (OR) or risk ratio (RR) —two reviewers extracted data corresponding to each factor, including factor definition, correlation strength index OR, RR, 95% confidence interval (CI), analysis method , and adjustment variables. Only the studies, which were provided OR/ RR values directly or calculated OR/RR values based on the study data, were included. If there was a univariate or multivariate analysis, the multivariate results were considered first. Analysis results after the adjustment for covariables were preferred. If the OR/RR values could not be extracted directly from the original text, we extracted the original data. The OR value of the determinant was then calculated using the original data. (3) Data conversion: according to the most common classification methods in the included studies or the existing classification standards of the study itself, the data of multiclassification were converted into binary classification data . The heterogeneity among the studies was evaluated using the Q test combined with IP-value of Egger's test (< 0.05) was considered an obvious publication bias.Sensitivity analysis was performed first using the one-by-one exclusion method, and then single-factor subgroup analysis and meta-regression were performed . In addition, regions were divided after considering economic differences. The division of years was based on a similar number of studies conducted around 2015. Funnel plots and Egger’s test were being used to evaluate and judge the publication bias of the factors mentioned in more than 10 studies. If the points on both sides of the funnel plot were funneled in the middle or approximately symmetrical, there was no obvious publication bias. The P < 0.05. The prevalence of consolidation and 95% CI were calculated using the total number of participants and the total number of EGWG occurrences for cohort studies using OpenMeta software [In this study, RevMan 5.3 and Stata 16.0 were used for the above statistical analysis, and the test level was set at software .th World Health Assembly of the World Health Organization (WHO); the determinants of EGWG were categorized into three themes—individual, family, and social factors [This study was based on the framework of the social determinants of health (SDH), which were proposed by the 66 factors . ConsideThe selection process is illustrated in the flow diagram shown in Fig. N = 7) and the rest were in English. The included studies were conducted in Americas (n = 33), Asia (n = 22), Europe (n = 11), Oceania (n = 3), and Africa (n = 1).The basic information for each included study is shown in Additional File In the 48 cohort studies, 3,053,581 women were investigated worldwide, 1,473,843 of them had EGWG, and the prevalence of EGWG was approximately 45.5% . Among the different regions, the prevalence of EGWG was highest in Americas, 49.8%  and Africa (55.20%), followed by Oceania at 49.0%  and Europe (42.3% 95% CI:35.9% − 48.6%), and the lowest prevalence in Asia at 38.2% .For full quality appraisal, see Additional File   According to the conceptual framework of the SDH, all factors were identified . After adjusting to the random-effects model, the results demonstrated that there was no correlation   was divided into overweight (including obesity), normal weight and underweight. Because the number of pregnant women with obesity was relatively small, the obese group and the overweight groups were combined. Women with prepregnancy overweight (including obesity) were more likely to develop EGWG at normal weight  and women with prepregnancy underweight had about half the odds of developing EGWG   and nonsmoking to perform a meta-analysis, and the probability of EGWG in pregnant women with smoking was 1.29 times higher than in those without smoking    Table .In America, Caucasians were more likely to develop EGWG than Blacks , 54, 55,One study reported that social support was found to be associated with weight gain during pregnancy , while aSeveral studies discussed the relationship between the payment mode of medical expenses and EGWG during pregnancy , 36, 49.Persistently low neighborhood deprivation was demonstrated to reduce the risk of developing EGWG . NeighboThe results of some factors for EGWG are presented in Additional File The consistency of education level and prepregnancy BMI (overweight/obesity) was confirmed by leave‐one‐out sensitivity analysis. However, the combined OR and 95% CI were not significantly affected in any of the study groups, and the difference was not statistically significant. This indicated that the above meta-analysis was stable and reliable Fig. .Fig. 3ThP < 0.05), suggested that heterogeneity may be related to different types of studies , the above meta‐analysis was also performed within subgroups of studies, defined by the region , type of study , and years . The subgroup analysis of the education level, combined with the meta-regression results , younger age, unemployment, primiparity, smoking, and unmarried (including divorced), while protective factors included prepregnancy underweight and inadequate antenatal care. There was no significant correlation between EGWG and education level, alcohol consumption, planning pregnancy, food security, and access to nutrition guidance during pregnancy.Prepregnancy BMI was the most concerning factor. Women with prepregnancy overweight (obesity) had a higher baseline weight and were more likely to experience EGWG , which wAge during pregnancy was also a key factor, and this study showed that younger patients had a higher risk of EGWG. This may be because older women have lower anabolism than younger women during pregnancy, or because younger women are less disciplined regarding lifestyle choices , 61. AlmThis study also found that being unmarried or divorced was a risk factor for EGWG. It may be that women with a lack of spouse’s company and family support, and do not pay enough attention to weight management during pregnancy. Furthermore, marital status was an important predictor of psychological symptoms and perceived stress in pregnant women . NecessaThis showed that unemployed pregnant women were more likely to develop EGWG. Unemployed women who live at home for a long time and do not have enough daily activities during pregnancy should be educated to modulate their lifestyle during pregnancy, and especially involve in modest exercise. Additionally, smoking was associated with an increased risk of weight gain during pregnancy. It is important in health education on healthy regarding lifestyle for pregnant women, to improve their understanding of diet and exercise during pregnancy, and guide them in developing the self-monitoring skills of diet and exercise.According to the WHO, about 10% of pregnant women worldwide have mental illness . PregnanIn addition, the included literature investigated the impact of domestic violence on EGWG. Domestic violence is not only a public health problem but also a serious social problem. The prevalence of domestic violence among pregnant women has been reported to range from 0.9% to 20% , and is Our study had a large sample size, and the determinants of EGWG were summarized comprehensively. Both qualitative description and data combination analyses were conducted. Furthermore, a meta-analysis of single group rates was also performed for the included cohort studies to obtain the global prevalence rate of EGWG comprehensively and accurately. Overall, the study used a uniform standard from the IOM for EGWG, and all included studies had a relatively high level of evidence through serious quality assessment. However, three items scored lower in cohort studies—ascertainment of exposure, assessment of outcome, and adequacy of follow-up of cohorts. In future studies, patients’ self-reports should be avoided as much as possible for the ascertainment of exposure, and fixed archival records or structured interviews are good options. For the assessment of outcomes, it is suggested to conduct a blind independent study and avoid subjective self-reporting. It is also important to strengthen the follow-up of the research, as much as possible to complete the follow-up. To obtain more accurate results, it is necessary to carry out high-quality original studies, collect quantitative data, perform an in-depth analysis of various factors, consider the confounding factors, and improve the reliability of research results in the future.Several limitations should also be noted: (1) Due to inconsistent research contents and grouping criteria, the data could not be combined for meta-analysis of some factors. Therefore, only a simple review was conducted, impacting the results of the analysis and the generalization of the conclusions. (2) When combining BMI, different studies used different methods of BMI classification . The BMI was not classified according to a specific index, but combined with those defined simply as the same category. (3) To compare and explain the effect of the determinants, the relevant data were transformed into two categories, which affected the accuracy of the results. Furthermore, the dose–response relationship of the studies was not considered. (4) The results from the forest map showed a high heterogeneity among the included studies, but the sources could not be well explained. Future research must explore the sources of heterogeneity.The high prevalence of EGWG in pregnant women remains a growing public health issue, showing the importance of preventive interventions regardless of the timing of pregnancy-related weight changes throughout life. This study was based on 70 observational studies with medium and high-level evidence, and found that EGWG was associated with 58 individual, family, and social factors. The risk factors for EGWG included the prepregnancy overweight (including obesity), younger age, unemployment, primiparity, smoking, and being unmarried (including divorced) in the meta-analysis. Protective factors that yielded some support included prepregnancy underweight and inadequate antenatal care. Therefore, it is important to avoid exposure to risk factors from multiple perspectives and develop pregnancy weight management interventions around the identified factors. Future solutions in EGWG likely require a greater focus on behavior change and maintenance.Additional file 1. Search strategy.Additional file 2. Basic information of included literature.Additional file 3. Quality assessment of included studies.Additional file 4. Supplementary findings.Additional file 5. Forest plots of pooled ORs in various factors.Additional file 6. The results of publication bias.