P < 0.001 on 5 of 6 factors). Depending on the level of engagement, the rate of weight loss over time differed for AU/NZ and UK/IE compared to the US. Our findings have important implications for the use and understanding of digital weight loss interventions worldwide. Future research should investigate the determinants of cross-country engagement differences and their long-term effects on intervention outcomes.Mobile health  interventions are ubiquitous and effective treatment options for obesity. There is a widespread assumption that the mHealth interventions will be equally effective in other locations. In an initial test of this assumption, this retrospective study assesses weight loss and engagement with an mHealth behavior change weight loss intervention developed in the United States (US) in four English-speaking regions: the US, Australia and New Zealand (AU/NZ), Canada (CA), and the United Kingdom and Ireland (UK/IE). Data for 18,459 participants were extracted from the database of Noom's Healthy Weight Program. Self-reported weight was collected every week until program end (week 16). Engagement was measured using user-logged and automatically recorded actions. Linear mixed models were used to evaluate change in weight over time, and ANOVAs evaluated differences in engagement. In all regions, 27.2–33.2% of participants achieved at least 5% weight loss by week 16, with an average of 3–3.7% weight loss. Linear mixed models revealed similar weight outcomes in each region compared to the US, with a few differences. Engagement, however, significantly differed across regions ( While initially concentrated in the United States, obesity has now also become a pervasive health concern for countries around the world . The preOne of the most effective treatments for obesity is lifestyle modification . ThroughThis understanding, however, inherently assumes that mHealth interventions deliver equally effective care to anyone anywhere in the world. Almost all meta-analyses, systematic reviews, and commentaries about mHealth mention that a significant benefit of mHealth is its scalability, or generalizability to other populations and even other countries. Many claims are made, such as that “with little or no loss in effectiveness,” mHealth interventions developed in one place “can transcend time, culture, and language: they can be used simultaneously anywhere in the world” as is , or thatIt is crucial to test this widespread assumption that mHealth interventions have similar outcomes in other countries, given the enormous costs of obesity for countries worldwide and the importance of providing the most effective treatments possible. Cross-country comparisons of mHealth intervention outcomes are lacking and focused on obesity prevalence rather than intervention outcomes. In addition, meta-analyses and systematic reviews make broad claims based on heavily US-centric data. For example, in one systematic review, 15 studies were conducted in the US, 2 in the UK, and one each in Australia and China . Thus, iIn particular, there is little work comparing whether an intervention primarily developed in one country  can result in comparable outcomes in other similar countries around the world. Given how culturally adapted interventions can be effective , it is iThe study also sought to advance understanding of cross-country mHealth differences by examining engagement. Engagement is a critical determinant of intervention success. Several studies have found that increased engagement, such as logging meals or steps, contributes to increased weight loss , 29. PasIn this study, we compare outcomes over the course of the Noom intervention in four English-speaking regions, spanning a total of six individual countries. We explore how weight compares over time in each region in comparison to the US. We also examine whether differences exist across countries in engagement levels and consider how engagement is associated with weight over time. Based on previous research showing similarities in weight loss across regions , 16, we The US was selected as a positive control comparator to test whether the intervention is as effective in other countries. Then, to allow for a non-biased comparison , the following countries were chosen: Canada, Australia, New Zealand, the United Kingdom (comprising Great Britain and Northern Ireland), and Ireland. These countries are similar to the US in the baseline prevalence of overweight and obese individuals , the main spoken language (English), and the prominence of Western foods . Thus, dSimilarly to past work, the following countries were combined in analyses based on geographic and cultural similarities: United Kingdom and Ireland (UK/IE), as well as Australia and New Zealand (AU/NZ). It is important to note that though these countries are geographically close, they can differ on cultural factors, climate, and ethnic makeup, among others. The regions included in this study were: the US, UK/IE, Canada, and AU/NZ.Noom is an mHealth behavior change intervention that utilizes in-app tracking features such as food and weight logging, virtual 1:1 health coaches, behavior change techniques, and education on diet, physical activity, and psychology to enable multi-component healthy lifestyle modification. The intervention draws from CBT, third wave CBT such as DBT, and motivational interviewing techniques. These techniques are particularly used by coaches and the curriculum, which covers general psychological and behavior change principles as well as those related to diet, physical activity, and weight management. Coaches trained in CBT and motivational interviewing techniques help users to set effective goals, identify barriers, and oversee users' progress . CoachesParticipants in all regions had access to all of these intervention components. To ensure that participants could use logging features, imperial measurements were replaced with metric measurements. Aside from this, the intervention was not culturally adapted to each country or region in order to test whether the intervention as is could effectively be applied to other countries.2) or healthy (18.5–24.9 kg/m2); if they were using the free version of the app, meaning they did not have access to the full intervention; and/or if they did not input baseline characteristics (gender and height). In addition, as in previous work, outliers were excluded, defined as an individual whose magnitude of BMI change was >3.5 within 1 month  program based on their own motivation to lose weight. All of these participants provided informed consent that their de-identified data could be used in a longitudinal study and were given the option to opt out during the initial sign-up process for Noom. Participants were included in the study if they met the following criteria: they were between 18 and 60 years of age, began the HW program in May or June of 2019, and had at least 1 in-app action and 1 weigh-in every week over the 16 weeks of the program as a minimum threshold of activity. Data for 32,983 potentially eligible participants was pulled from Noom's database  and de-identified . Participants were considered ineligible if their initial weight classified their body mass index (BMI) as underweight , age (P = 0.008), and height (P < 0.001). Initial weight (in kg) significantly differed across regions (P < 0.001), with the highest baseline weight in the US  and the lowest in AU/NZ . Similarly, baseline BMI differed across regions (P < 0.001), ranging from a mean BMI of 30.27 (SD = 4.59) in the US and 30.14 (SD = 4.56) in Canada to 29.46 (SD = 3.62) in AU/NZ and 29.47 (SD = 4.13) in UK/IE. The final linear mixed model accounted for these differences in baseline characteristics.Descriptive baseline characteristics, along with significance tests across regions, are displayed in Descriptive statistics for weight loss over the 16 weeks are displayed in B = −0.018, 95% CI: −0.19 to −0.18, and P < 0.001), such that weight decreased 0.02 kg per week over the 16 weeks. Characteristics such as age , baseline BMI , and gender  significantly predicted weight throughout the 16 weeks. There were no significant main effects of region for AU/NZ and UK/IE; however, participants from Canada lost a significant amount of weight compared to US participants. Across time, AU/NZ and UK/IE participants did not significantly differ in average weight compared to US participants. On average across time, US participants weighed 0.71 kg more than Canadian participants .In the linear mixed models, we observed significant main effects predicting weight loss as well as significant interaction effects that provide more explanation for the main effects . For maiB = 0.07, 95% CI: 0.03–0.12, and P < 0.001). Thus, US participants lost 0.07 kg more than AU/NZ participants over time, while Canadian and UK/IE participants did not differ from US participants in weight loss over time.Examining interactions with time allowed further exploration of weight loss over the course of the program, instead of averaged across time in main effects. Two-way interactions of time * region revealed that over time, Canadian, and UK/IE participants did not significantly differ in weight loss compared to US participants. The only significant region * time interaction was a AU/NZ * time interaction , while AU/NZ participants had the fewest messages to their coaches , P < 0.001. In addition, UK/IE participants logged the most steps , P < 0.001.Notably, participants engaged with the intervention differently across regions. One-way ANOVAs revealed that were significant differences in the average amount of engagement on five of six factors: average number of articles read, steps recorded, days with weigh ins, number of messages to the coach, and number of times they exercised each week  was modified by the three way interaction between engagement, region, and time. Engagement appeared to matter more for US participants than UK participants  and AU/NZ participants  in predicting weight throughout the 16 weeks. With a one unit increase in engagement, US participants lost 0.01 kg more than AU/NZ participants and 0.006 kg more than UK participants over time. A two-way interaction between engagement and time was also found . Higher engagement predicted greater weight loss over time, such that one unit increase in engagement was associated with a decrease of 0.02 kg in weight over time, regardless of region of origin. No significant two-way interactions between region and engagement were found, meaning the effect of engagement on weight did not significantly differ among regions without incorporating time. These cross-region differences in engagement and weight loss are summarized in In the linear mixed models, a significant engagement effect  and 3.7% (3.69 kg) in all regions, matching the results of a previous study on this intervention that generated 3.5% weight loss by week 16. This is on track to surpass 5% weight loss by 1 year , which eWhile no previous cross-country comparisons of an mHealth weight loss intervention existed prior, the verifiable portions of our results replicated past findings. Matching strong patterns in the literature, we found significant associations between weight and baseline BMI, gender, age, and engagement over time , 38, 39.Beyond differences in demographics, there were region-level differences in how participants actively engaged with the program. For example, UK/IE participants logged the most steps and Canadian participants had the highest messages to coaches. This could be for several reasons, for example differences in sociability, time zones, and seasonality. To our knowledge, there is no prior work showing differences between the regions included in this study in terms of coach messaging. Our results with UK/IE participants and steps aligns with a study leveraging automatically recorded smartphone activity data. Results showed higher step counts in the UK than in the US . Future With regard to engagement cross-culturally, only one other study compared participants from Finland and India and found that while individuals had similar attitudes toward weight loss, they had very different culturally-induced engagement behaviors in a mobile physical activity app. For instance, because Indian participants viewed health as oriented around routines and not goals, they used the app's goal setting functions of the app much less than Finnish participants . Other pAnother reason for cross-region differences in engagement could relate to cultural tailoring. According to previous research, interventions that are specifically adapted for certain populations or locations can be effective . Aside fWith the association between engagement and weight loss found in previous research and replicated in our results, it is notable that we did not just find a two-way interaction with engagement and time. Rather, we saw an additional three-way interaction with region. With high engagement, the rate of weight loss was the fastest in the US compared to AU/NZ and the UK/IE. This aligns with rare cross-cultural work, such as a study that used self-reported survey data. Results showed that US participants had greater familiarity with mHealth apps than UK participants . PerhapsThis study had several strengths. First, in using this retrospective design, the study could explore participants' behaviors with a weight loss intervention that they were using without researcher supervision, contact, or being alerted to participation requirements along study time points. This could increase external validity of real-world conditions and contribute rare data to the literature. In addition, the study analyzed intervention effects in ways that captured the complexity of the relationships of weight loss over time, engagement, and region. Rather than merely averaging across time points or conducting one multiple comparison test in the change in weight loss at week 16, we found a more sophisticated picture of results when analyzing weight loss over time and investigating interactions with engagement. Finally, the study's extensive sample size provides greater confidence in generalizability than typical intervention studies.The study has a few limitations. First, because the intervention was developed in the US, the sample was heavily skewed toward US participants. Seventeen thousand two hundred and forty out of 18,459 participants (93.4%) were from the US; in comparison, 431 (2.3%) were from Canada, 375 (1.0%) from Australia/NZ, and 597 (3.2%) from UK/IE. While significant interaction effects were still found with these sample sizes and they are larger than typical intervention samples, our analyses may not have captured the full range of variation in these regions. The US skew in our sample also limits generalizability of our findings. Future research should extend our findings to samples that are more equally distributed. Another limitation of the study is that no active control group was used, which means causal interpretations of the effect of Noom cannot be made, particularly in relation to the superiority of Noom compared to usual care. Future studies should use active control groups to assess the difference between the intervention and control groups across countries. Additionally, only participants in these regions who were interested in a mobile health intervention for weight loss signed up for the program and were included in the study. This same self-selection bias would apply to all four regions and the population of individuals who participate in interventions, but future studies should determine if this bias manifests differently in each of the regions. The study also used the user population of one program. While the number of participants was larger than many typical studies, the population was nevertheless naturally restricted to those who self-selected into this particular program. Future research should examine whether the results generalize to other interventions in other regions beyond these four. In addition, only one time period of 16 weeks was used. Future work should incorporate multiple time periods to explore whether cross-country effectiveness remains consistent over different periods of time and seasons. Further, the sample only included participants who met a minimum criteria of in-program activity for 16 weeks, which limits generalizability to individuals who meet this criteria. Finally, within each individual country, individuals may differ greatly on culture, primary language, country of birth, and ethnicity, which could affect engagement in ways we could not capture in this study; future studies should explore these differences and how they affect engagement.This study provided a necessary test of a widespread implicit assumption in the literature, with important implications for how digital weight loss interventions are applied, understood, and designed worldwide. Our results provide preliminary evidence that the same mobile intervention can induce comparable weight loss in other regions or countries. In addition, even though weight loss was similar, there were country-level differences in the way people engaged with the intervention. Even with similarities of language and Western cultures, there are differences that need to be understood better in applying mHealth interventions across countries or regions. This reveals important areas of investigation for future obesity research, such as the factors determining cross-country differences in engagement, and the impact of these engagement differences over time in predicting weight.siobhan@noom.com.Data were obtained from Noom, and legal and proprietary restrictions apply to the availability of these data. Requests to access the data should be directed to Siobhan Mitchell, The study was approved by Advarra Institutional Review Board. The participants provided informed consent to participate in this study.QY conducted data analysis, data interpretation, and contributed to study conception and study design. EM conceived the study and contributed to study design and editing. AH performed literature searches and wrote and edited the manuscript. LD, HB, and AM contributed to study conception, study design, and editing. All authors contributed to the article and approved the submitted version.QY, AH, EM, LD, HB, and AM are employees at Noom Inc.


Chronic pain is one of the most common health problems for older adults worldwide and is likely to result in lower quality of life. Living in a different culture may also influence chronic pain and quality of life in older adults. The purpose of this study was to explore how multifaceted elements affect chronic pain and quality of life in older Koreans living in Korea and in older Korean–Americans (KAs) living in the USA.We conducted a secondary data analysis of data from 270 adults aged 65 years or over (138 Koreans and 132 KAs). We compared the effects of multifaceted elements on pain and quality of life by testing structural equation models (SEMs) for each group, using a maximum likelihood estimation and bootstrapping.SEMs for both Korean and KAs showed that age and depressive symptoms directly affected quality of life. The number of comorbidities and depressive symptoms had mediating effects on quality of life through chronic pain in both groups. In older Koreans only, perceived financial status directly affected quality of life. In older KAs only, sleep quality indirectly affected quality of life through chronic pain.The data showed that multimorbidity and depressive symptoms play critical roles for explaining chronic pain in older Koreans and KAs and ultimately negatively influence quality of life. Future intervention program to improve quality of life in older adults with chronic pain should consider the different cultural aspects affecting quality of life for Koreans and KAs. Persistent, recurrent chronic pain affects 39–70% of older adults worldwide –4 and neA biopsychosocial approach to pain is a well-known theoretical framework for understanding multi-dimensional aspects of pain . A rangeTo better understand chronic pain and improve quality of life in older adults with chronic pain, a comprehensive approach that considers multifaceted elements affecting pain and quality of life should precede within a sociocultural context. In this study, we aimed to explore how multifaceted elements, including biological , psychological , and social  aspects, affect chronic pain and quality of life in older adults with who have chronic pain and the same ethnicity, but who are living in different cultures Fig. . We deveThis study was a secondary data analysis of cross-sectional data from a previous study for exploring intra-ethnic differences in chronic pain and associated factors . In ordeA total of 270 older adults  participated in the original study. Older adults (≥ 65 years of age) with chronic pain for the last 3 months, no cognitive impairment on the Mini-Mental Status Examination (score ≥ 24) were included in the study. Older adults with severe medical conditions, such as uncontrolled hypertension and acute pain, daily opioids use, or acute symptoms that interfered with data collection were excluded from the study. Although the participants were recruited in Korea and the USA simultaneously, they were not matched.The sample size requirements for the structural equation modeling approach have diverse rules-of-thumb methods, such as 5–15 cases per measurements variable –23. GiveFor this study, we retrieved data from the original study on: age, gender, perceived financial status , the number of comorbidities, and the level of acculturation (for only older KAs) . The levThe Korean version of the Patient Health Questionnaire-9 was used to assess the level of depressive symptoms in older adults . This seSleep quality of the participants was assessed by the Korean version of the Pittsburg Sleep Quality Index . Among 2The Korean version of the Brief Pain Inventory-Short Form was used to assess two domains including the pain severity and pain interference . Four itThe Korean version of the Euro Quality of Life Questionnaire 5-Dimensional Classification-3L (EQ-5D) was used to assess quality of life . This meData collection for the original study was carried out from November 2018 to March 2019 in Maryland, U.S., and Seoul, Korea. The participants were simultaneously recruited from a senior welfare center in Seoul, Korea, and from multiple sites, including Korean senior centers, Korean churches, and elderly day care centers, in Maryland, U.S. The recruitment places were selected to make the functional status of the participants in Korea and in the USA similar. Basically, the participants filled out the questionnaires by themselves; however, the researchers assisted the completion of the questionnaires when the participants want.The original study was approved by the institutional review boards (IRBs) at the Towson University in the U.S.  and Seoul National University in Korea (1808/002-009). This secondary data analysis was also approved by the IRB of the Seoul National University (E2005/003-006). When the older adults showed a willingness to participate in the study, the researchers provided sufficient information on the study purpose, time for the survey, possible benefits and risks, and freedom of voluntarily withdrawal from the study without any disadvantage. Among those who understood the purpose of the study and wished to participate in it, the researchers screened the eligibility in accordance with the inclusion and exclusion criteria. Then, written informed consent from all participants was obtained.IBM SPSS version 23.0 and AMOS version 23.0 were used to analyze the data. First, all data were reviewed to check for the presence of missing values. Approximately 0.2% of the data were missing, so they were dealt with expectation–maximization. Background characteristics and all study variables were described by mean and standard deviation for continuous data and frequencies and percentage for categorical data. They were also compared by groups (Koreans vs. KAs) using independent t-tests or chi-square tests. In order to check the assumptions for a structural equation modeling analysis, variables including age, the number of comorbidities, depressive symptoms, sleep quality, perceived financial status, acculturation, pain, and quality of life confirmed no signs of multicollinearities using Pearson correlation analyses, and normality using skewness and kurtosis. Then, the measurement equivalence among two groups, which indicates comparability of measurement in the cross-national study , 32, wasχ2 below 3, goodness of fit index (GFI) above 0.90, normed fit index (NFI) above 0.90, comparative fit index (CFI) above 0.90, incremental fit index (IFI) above 0.90, and root mean squared error of approximation below 0.10 in each model [β), standard errors (S.E.), critical ratio (C.R.), and squared multiple correlations (SMC). In addition, the multifaceted elements, including biological , psychological , and social  aspects on chronic pain and quality of life, were examined for direct, indirect, and total effects, which were reported by standard regression coefficients (β) and p-values. Acculturation was input in the model of KAs in this study.The structural equation model in each group was using a maximum likelihood estimation and bootstrapping. The model fit was evaluated using multiple indices including relative ch model , 33. TheThe mean age of the Korean participants was 75.60 years, and the mean age of the of the KA participants was 78.33 years Table . Most ofThe mean depressive symptoms score was not significantly different between the two groups (4.39 for Koreans and 5.55 for KAs). The mean scores for the other variables were significantly different between the two groups: sleep quality , chronic pain severity , chronic pain interference , quality of life , and self-rated health status  .The results of the structural equation models in older Koreans and KAs with chronic pain appear in Fig. β = .231, p = .003) and depressive symptoms . In addition, each path from age , depressive symptoms , perceived financial status , and chronic pain  to quality of life in Koreans was significant.In the model for Koreans Fig. , there wβ = .170, p = .019), the number of comorbidities , depressive symptoms , and sleep quality . In addition, each path from age , depressive symptoms , and chronic pain  to quality of life in KAs was significant.In the model for KAs Fig. , there wβ = .231, p = .034) and depressive symptoms  had direct and total effects on chronic pain. Among the variables that had total effects on quality of life, including age , the number of comorbidities , depressive symptoms , and chronic pain , the number of comorbidities and depressive symptoms indirectly affected quality of life through chronic pain even though they did not directly affect it.Standardized direct, indirect, and total effects in each model are summarized in Tables β = .170, p = .011), the number of comorbidities , depressive symptoms , and sleep quality  had direct and total effects on chronic pain. Among the variables that had total effects on quality of life, including age , the number of comorbidities , depressive symptoms , and chronic pain , the number of comorbidities and depressive symptoms only indirectly influenced quality of life through chronic pain, as in the model for KAs. Although sleep quality had an indirect effect on quality of life through chronic pain, the total effect was not significant.In the model for KAs Table , age , psychological , and social  aspects, affect chronic pain and quality of life in older adults with chronic pain and that there were no cultural effects on chronic pain and quality of life in older adults who had the same ethnicity, but were living in different cultures. Some suggestions can be made based on the findings of this study. First, healthcare providers who come across older adults with chronic pain should examine affecting factors and relationships from various standpoints. In particular, when targeting older immigrants, healthcare providers should carefully assess older immigrants’ acculturation level using a valid measurement and consider integrating the acculturation level into an intervention program for alleviating chronic pain and improving quality of life. Further studies are needed to examine more comprehensive variables affecting quality of life in older immigrants with chronic pain. In addition, further studies are needed that use multiple measurements, such as a combination of direct  and indirect  measurements, to provide a more accurate and extensive view of quality of life.


Obstructive sleep apnea (OSA) and atrial fibrillation (AF) are epidemiologically correlated, but the causal relationship between them remains elusive. We aimed to explore the causal relationships between OSA and AF.Using both the Finnish biobank and publicly available genome-wide association study data (GWAS), we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal effect of OSA on AF, both in the primary analysis and replicated analysis. The inverse variance weighted MR was selected as the main method. To further test the independent causal effect of OSA on AF, we also performed multivariable MR (MVMR), adjusting for body mass index (BMI), hypertension, and coronary artery disease (CAD), respectively.In the primary analysis, OSA was significantly associated with the increased risk of AF  and the replicated analysis showed consistent results . Besides, there was no heterogeneity and horizontal pleiotropy observed both in the primary and replicated analysis. Further multivariable MR suggested that the causal relationships between OSA and AF exist independently of BMI and CAD. The MVMR result after the adjustment for hypertension is similar in magnitude and direction to the univariable MR. But it did not support a causal relationship between OSA and AF.Our study found that genetically driven OSA causally promotes AF. This causal relationship sheds new light on taking effective measures to prevent and treat OSA to reduce the risk of AF. Atrial fibrillation (AF) is the most common type of arrhythmia that causes hemodynamic disorders, thrombotic strokes, heart failure, and increased mortality , with anNotably, OSA is characterized by recurrent episodes of airway collapse during sleep, the combined prevalence of OSA in patients with AF has been estimated at 21 to 74% , 7. A feBased on the deficiency of the former studies' design, we considered Mendelian randomization (MR). MR can be used to resolve causal assumptions. It is a genetic instrumental variable analysis that can evaluate the potential relationship between exposure and outcome . As MR uThe overview of this study design is presented in https://www.finngen.fi/en), a large study aiming to collect and analyze genome and health data from 500,000 Finnish biobank participants. We identified 5 single nucleotide polymorphisms (SNP) robustly associated with OSA in the FINNGen genome-wide association study that included 217,955 participants ; r2 < 0.001, LD distance > 10,000 kb]. F statistic {calculated as F = [(n-k-1)/k]/[R2/(1-R2)], the explained variance for exposure (R2), sample size (n), and number of SNPs (k)} indicates the strength of the relationship between SNP and OSA. In general, F-statistic >10 indicates a significant association between selected instrumental variables and OSA . We extracted exposure data from the FINNGen consortium , nearly all of European ancestry. And the summary data on CAD we used was from a large meta-analysis of GWAS which includes 141,217 individuals of European ancestry  with R packages “TwoSampleMR”, and “MVMR”. A two-tailed p-value < 0.05 was considered statistically significant.Mendelian randomized (MR) analysis was performed in R  (2 = 0.083 in this study), the minimum detectable OR was roughly estimated. The results of the power calculations are shown in To evaluate the power of our study, a non-centrality parameter-based approach was used, which is a publicly available mRnd web tool (y/mRnd/) . For binThe characteristics of the populations included in the FINNGen and GWAS data of outcomes are shown in P < 0.05 in the four MR methods, including MR-Egger, IVW, Weighted median, and Weighted mode). OSA was associated with an increased risk of AF . For the replicated analysis, there was still clear evidence to support a causal effect between OSA and AF . The OR and 95%CI of OSA were 1.17 (1.05–1.30) for incident AF risk.The overall results of the univariable MR are shown in Ph = 0.386, Pintercept = 0.236). The results of the replicated analysis were consistent with the primary analysis, with no heterogeneity or horizontal pleiotropy found . Besides, the MR-PRESSO results showed no outlier SNPs. In the leave-one-out analysis, we found that no single SNP was strongly driving the overall effect of OSA on AF in the primary analysis . The replicated analysis showed similar results to the primary analysis above . And the adverse effect of OSA on AF existed after adjustment for CAD . However, there was no evidence in favor of an association between OSA and AF after adjustment for hypertension  patients with obesity, found a 3 or 4.8% prevalence of nocturnal AF, higher than that of 0.4–1% in the general population , 30. As There are several pathophysiologic mechanisms underlying the causal OSA-AF relationship. Apnea directly induces acidosis, hypoxia, hypercarbia, and elevated pulmonary pressure, subsequently resulting in combined sympathovagal activation contributing to hemodynamic and arrhythmogenic electrophysiologic changes, increasing the frequency of premature atrial contractions with the potential to initiate AF in a vulnerable substrate –42. FurtTo note, some points in the data aroused our consideration. Effect sizes for the presence of OSA on the AF risk in our MR analysis were smaller compared with those obtained using observational data. This might be attributed to several reasons: part of AF is hard to capture when paroxysmal and might remain silent or asymptomatic in clinically stable patients or outpatients. Based on this background, cohort studies with closer follow-up of the participants had more opportunities to document more AF cases than those in our population. Meanwhile, another explanation is related to confounding-derived bias on the association between OSA and AF described above in observational studies. Multivariable MR association persisted after additional adjustment for comorbidities that may either mediate or confound the OSA-AF relationship, effect estimates were similar after BMI and CAD adjustment, but hypertension adjustment abolished the efficacy, suggesting that HTN might substantially mediate the effect of OSA on the risk of AF. It made sense that recognition already suggested that one of the OSA complications was a higher frequency of non-dipping blood pressure (BP) and pattern nocturnal hypertension , and genOur study has some limitations. First, the limited number of instrumental SNPs in our study may distort MR estimates. But the F statistic of the SNP we used in this study were all >100, suggesting a strong correlation with OSA. Second, it is unlikely to remove all potential horizontal pleiotropy from the study, which may result in the biased estimation of causal inference. However, no pleiotropic effect was detected in the MR-Egger regression. Third, the specific ancestry of the samples also limits the generalizability of our results to other ancestries. Despite relative weaknesses, our study has several noteworthy advantages. First, we used MR method to estimate the causal effect between the OSA and AF, which contributes to the avoidance of measurement errors and residual confusion. In addition, we performed a series of sensitivity analyses to assess heterogeneity and pleiotropy, and we also conducted MVMR to correct for the effects of confounding factors including BMI, hypertension, and CAD.In summary, the current study provides the first causal evidence of the relationship between genetically predicted OSA and the risk of AF, suggesting that the therapy of OSA might represent an effective strategy to lower the incidence and re-occurrence of AF.The original contributions presented in the study are included in the article/YLi, YLe, and RM drafted the manuscript. YLi and HT analyzed the data. PM, RM, and HT designed the study. PM and HY obtained the funding. All authors participated in the field survey and data collection, critically revised the manuscript, and gave final approval to the version submitted for publication.This work was supported by the National Natural Science Foundation of China (81974054), Liaoning Province's Xingliao talent program in China (No. XLYC1807116), and the Fundamental Research Funds for Central Universities of Central South University (2019zzts106).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Functional constipation (FC) is a common bowel disorder that prevails worldwide. In China, although a heterogeneous prevalence of constipation is expected, it is currently not demonstrated. In this study, we aimed to evaluate the prevalence and related risk factors of FC in the Chinese population, according to the Rome criteria.We searched the PubMed, the Embase, the Cochrane Library, the Web of Science, the China National Knowledge Infrastructure (CNKI), the Wanfang data knowledge service platform, the VIP information resource integration service platform, and the Chinese Biomedical Literature Service System (SinoMed) databases from the inception of database to July 2021. Population-based cross-section studies that enrolled adults with FC, diagnosed by the Rome criteria, were deemed eligible. We summarized the overall prevalence and detected the subgroup effect per the Rome I, Rome II, Rome III, and Rome IV criteria. We used the generalized linear mixed model (GLMM) with a random-effect intercept to pool the prevalence and performed pairwise meta-analyses for prevalence comparisons by risk factors.We identified 3,213 records through our database search, and 39 studies from China, comprising 1,240,79 participants, met the eligibility criteria for our study. The pooled overall prevalence of FC using the Rome criteria was 8.5% in China. Heterogeneous prevalence was detected within the Rome criteria . The prevalence increased between 1991 and 2020 (from 5.5% with 95% CI: 3.6–8.2 between 1991 and 2000 to 10.9% with 95% CI: 5.5–20.4 between 2011 and 2020). Higher prevalence was found in women  and the elderly  than in men and the younger population. A high-fiber diet was associated with lower prevalence , whereas irregular bowel habit and inactivity were associated with higher prevalence . Unhealthy mental states, such as anxiety and depression, and poor sleep quality led to high prevalence .Various types of FC prevail in China based on the different Rome criteria, personal characteristics, and habits. The prevalence also increased over the past three decades. The FC should be included under the primary care setting with uniform diagnosis criteria in China.http://www.crd.york.ac.uk/PROSPERO, CRD42021277172. Constipation, a common symptom among the general adult population, is defined as a bowel disturbance characterized by hard or dry stools, infrequent bowel movements, and incomplete bowel evacuation –3. ConstThe Rome criteria followed evidence-based medicine and provided clear decision-making standards and definitions for clinical practice, which were recognized and generalized by clinical researchers , 7. WithThe FC places a considerable economic burden on health care resources , 12, 13.With rapid economic development in China, the prevalence of constipation has increased in China and has now become a serious public health issue . AlthougAn updated systematic review on the global prevalence of FC suggests that its prevalence with uniform symptom-based criteria still varies considerably among countries . Thus, twww.crd.york.ac.uk/PROSPERO). We carried out this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines (The protocol of this systematic review (register number: CRD 42021277172) was registered in PROSPERO , the Wanfang Data Knowledge Service Platform, the VIP information resource integration service platform, the Chinese Biomedical Literature Service System (SinoMed), the English electronic databases, the PubMed, the Embase, the Cochrane Library, and the Web of Science, from their inception to July 2021, to identify the population-based cross-sectional studies that reported the prevalence and related risk factors of FC diagnosed according to the Rome criteria in adult populations in China. The search strategy was applied by two independent investigators (ZC and YP), and a third researcher (CL) was responsible for resolving any disagreement. The search terms were a combination of MeSH terms and free text, as discussed by the specialist consensus on the search terms, which included “constipation,” “chronic constipation,” “functional constipation,” “idiopathic constipation,” “bowel disorders,” “functional gastrointestinal disorders,” etc. Additionally, the following terms related to the Rome criteria were also used: “Rome I,” “Rome 1,” “Rome II,” “Rome 2,” “Rome III,” “Rome 3,” “Rome IV,” and “Rome 4.” We also manually retrieved data from the included cross-sectional surveys to supplement the literature and ensure a comprehensive search. There were no language restrictions. We translated the literature published in languages other than Chinese to understand it better. More detailed information of search strategy is reported in We included studies if the prevalence and related risk factors of FC were reported in the general population or community population. To be eligible, recruitment should have been conducted in China, including Mainland China and Taiwan Province, to recruit the eligible healthy adult Chinese (age older than 18 years). Further, studies that recruited more than 100 participants were included. We also included studies that reported the prevalence of functional gastrointestinal disorders or bowel disorders or incidence of FC diagnosed using the Rome criteria. All the included studies were conducted on humans.Ineligible participants included college students, special professionals , people undergoing health checks in primary care clinics due to illness or poor physical condition, participants under 18 years, and pregnant women. We also excluded studies where the diagnostic criteria of FC were unclear and self-defined and excluded studies that focused on irritable bowel syndrome with constipation (IBS-C).The title, abstract, and the full text of eligible articles were independently screened by two investigators (ZC and YP). All data from the eligible articles were extracted according to the prespecified eligibility criteria and checked by a third investigator (QS) for accuracy and completeness. When data from multiple studies were obtained for the same group of participants, we chose the studies with more detailed information. We contacted the authors of papers with ambiguous information or missing data. Any inconsistencies were resolved and discussed until a panel of researchers (CL and JZ) reached a consensus.The following data were extracted: study characteristics , basic information of participants . Data extracted from related risk factors included the following: dietary habits , living habits , working conditions , related diseases , unhealthy behavior , and self-management behavior.I2 and Q statistic for quantifying and testing the heterogeneity. The funnel plot with Egger's and Begg's test quantified the publication bias; we then used trim and fill analysis, if the bias was detected.We used the generalized linear mixed model (GLMM) with the random-effect method and fixed-effect method to pool the single group proportions for the included studies. The proportion was modeled by a logit transformation in GLMM. The between-study variance was estimated using the DerSimonian-Laird estimator with corresponding Several subgroup analyses were introduced, including the province, Rome criteria, sampling year, sampling method, questionnaire method, gastrointestinal disease type, and check if the questionnaires were validated or not.Several comparisons of prevalence were performed according to the following factors: (1) general information, such as sex, age, education, socioeconomic status, and BMI; (2) diet, including high-fiber or not, meat intake or not, and water intake is regular or not; (3) lifestyle habit, including physical activity, work habits, and bowel movement, (4) related diseases, including mental status, cardiovascular diseases, gastrointestinal diseases, and endocrine diseases; and (5) smoking and drinking habit. These parameters were compared using the OR with 95% CI from pairwise meta-analyses using the Mantel-Haenszel pooling method.All analyses were done using R 4.0.5 with a meta package.We identified 3,213 citations by searching the databases and found 19 additional studies on running a manual search. Of these, we identified 39 studies that reported the prevalence of FC among the general adult populations, after being appraised and assessed for eligibility. The results of the search are summarized in I2 = 99%, P = 0) , with significant heterogeneity  . The pooAll information of prevalence that was stratified by study settings is shown in Most studies reported the method of questionnaire administration, with 27 studies using the interview-administered questionnaire , and five studies using the self-administered questionnaire . There were eight studies reporting the method of questionnaire administration with unclear data .Three of all the included studies reported that they used a validated questionnaire, and 36 studies had not reported the validation status of the questionnaire. Compared to the validated questionnaire , the prevalence of FC was almost approximated in studies that used the non-validated questionnaire .We summarized three sampling methods in this meta-analysis, with 15 studies using stratified and random sampling , 12 studies using random sampling only , and 12 studies using the convenience sampling .For all eligible studies, we divided the research on various disease types into two categories: 27 studies that only focused on constipation with an unexpectedly high prevalence of FC  were compared with 12 studies that focused on constipation and other gastrointestinal disorders .The pooled prevalence of individual provinces in China, according to the Rome criteria, is shown in The characteristic-specific prevalence estimates of FC are shown in I2 = 0 %, P = 0.81). We found that the OR for FC in patients whose drinking water intake was moderate or high was 0.34 (95% CI: 0.10–1.14) and 0.35 (95% CI: 0.14–0.87), respectively, compared to that in patients whose drinking water intake was low. There was a significant difference in drinking water in the morning vs. other times .Dietary habits are risk factors for FC; therefore, we analyzed the following related aspects . There wOther lifestyles that were reported were analyzed as follows and are also summarized in We assessed the effects of related disease with FC in this meta-analysis and the data are shown in The percentage of various self-management behavior of patients with FC for improving constipation were detected with differences. Among those with FC, the percentage of change in diets was the highest in 40.7% of patients (95%CI: 29.9–52.6), followed by self-medication behavior in 23.8% (95% CI: 13.9–37.5), no changes in 23.4% (95%CI: 14.8–34.8), and health-seeking behavior in 17.2% (95%CI: 11.5–24.8) of patients .P = 0.1054) and Begg's test (P = 0.2083). The funnel plot is shown in We found no significant publication bias for the overall pooled prevalence of FC by Egger test  observed in studies conducted between 2011 and 2020. Compared with self-administered and unclear questionnaires at 11.9% and 11.0%, the pooled prevalence of FC using the interview-administered questionnaire was higher at 7.3%. Our results suggested that the validation status of the questionnaire used had no significant impact on the prevalence of FC, but the sampling methods and various disease types of research influenced the prevalence. Furthermore, there were strong associations between the pooled prevalence of FC, age bands, and sex. Meta-analysis results suggest that the higher prevalence of FC was more common among women and the elderly, and the ORs were high in women and patients older than 50 years. Results of our study showed that the pooled prevalence of FC was not significantly different with changes in educational level, socioeconomic status, and BMI.We identified the potential benefits of a high-fiber diet  in reducing the risk of FC. We further present evidence that high meat intake was a significant risk factor for FC, with an increased OR of 2.92. The pooled prevalence of FC was strongly associated with dietary habits in our findings. The prevalence of FC was more commonly linked to infrequent physical activity, irregular bowel habits, and high working pressure, and there was no association between the pooled prevalence of FC and working status, labor types, smoking, and alcohol intake. We found that the FC was strongly associated with the abnormal mental state , dyspepsia, gastroesophageal reflux, and diabetes, and not related to coronary heart disease, hypertension, biliary tract disease, and hyperlipidemia. For self-management behavior in those with FC in China, they have changed in the diet by themselves from 2-fold to 3-fold greater than self-medicine behavior or health-seeking behavior.To the best of our knowledge, this is the first systematic review and meta-analysis to compile the pooled prevalence of FC diagnosed according to the Rome criteria in general adult populations in China. Some strengths of our study are that we used more granular data based on the Rome criteria for FC than that used in previous studies that reported non-uniformity in the diagnostic criteria and identified all available literature using rigorous methodology. The literature search was conducted independently by two investigators to judge all potentially eligible studies, ensure comprehensive and rigorous extraction of data, and facilitate consensus and discussion by a panel of researchers, if necessary. We used the GLMM method to pool the data, as this may provide a more precise estimation than other methods. We used information gathered from trial settings and the Rome criteria to estimate the pooled prevalence of FC and explored all significant risk factors: constipation-related lifestyle, disease, and self-management behavior. This study focused on the geographic region and the characteristics of the target population, and our results are fully applicable to Chinese individuals living in China.There were several limitations in our study. Although we analyzed all related risk factors reported in the included studies, there was a deficiency of information on other potential factors that might be strongly associated with FC, because of the limitations in those studies. Due to unavailable data in a limited number of studies, some subgroup analyses could not be conducted. Furthermore, only one study reported the prevalence of FC diagnosed according to the Rome IV criteria with the interview-administered and self-administered questionnaires. Since Rome IV was a new criterion for FC, there was a paucity of data with respect to studies for FC diagnosed with the Rome IV criteria in China. Owing to the lack of information in several provinces of China, the real prevalence of FC in these provinces was not precisely reflected, further affecting the accuracy of pooled prevalence. The high heterogeneity may be relevant in the differences among the related factors in individual studies, including study designs, different diagnostic criteria, and target populations. These limitations can be resolved through cross-sectional studies conducted in the future, with efforts made to interpret high-quality data. Another limitation of this study might be the low number of available studies and wide confidence intervals on possible risk factors.A previous and another updated systematic review were published in 2011 and 2021 by the same research team, which reported the global prevalence of FC as 14 and 15.3%, respectively , 11. DueFindings from this study have important implications for the health policy and clinical practice in China. This meta-analysis showed that people in China commonly experienced constipation. Based on our results, we suggest that future studies should comprehensively consider the risk factors for FC, using the Rome criteria. Patients sought improved quality of life and alleviated the symptoms of constipation by relying on self-medication and consultation, which may increase the burden on public health , 64. FurThrough this systematic review and meta-analysis, we have demonstrated that the pooled prevalence of FC was 8.5% in China, which varied from 6.5% obtained with Rome III criteria and 10.6% with the Rome II criteria. The FC was more common in women and the elderly. The prevalence varied significantly in different provinces and it had a steadily increasing trend between 1991 and 2020. Based on the support from ample data and evidence, a high-fiber diet, regular bowel movements, and physical activity significantly affect FC. Furthermore, our results confirmed that anxiety, depression, and poor sleep quality were strongly associated with constipation. More FC-related risk factors need to be investigated in the future. Although some variables are unclear, these data can help lay down health policy and improve clinical practices in China to reduce the burden on public health.The original contributions presented in the study are included in the article/ZC and CL conceived the writing ideas of this manuscript and designed this study. ZC and YP wrote the initial draft of this manuscript and conducted the data analyses. ZC, YP, and QS completed the literature retrieval and data extraction. YC, JJ, LC, CL, and JZ instructed and reviewed the manuscript at any stage of this study. All authors participated in the study and revised and approved this manuscript.This study was supported by the Young Qihuang Scholar Support Project of National Administration of Traditional Chinese Medicine and Special Support Plan for Talent Development of Tianjin—Young Top Talent Project (No. 201504).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Some persons developing, or presenting, schizophrenia engage in aggressive behaviour (AB) and/or criminal offending. Most of these individuals display AB prior to a first episode of psychosis (FEP). In fact, approximately one-third of FEP patients have a history of AB, some additionally display other antisocial behaviours (A+AB). The large majority of these individuals have presented conduct problems since childhood, benefit from clozapine, have extensive treatment needs, and are unlikely to comply with treatment. A smaller sub-group begin to engage in AB as illness onsets. A+AB persists, often for many years in spite of treatment-as-usual, until a victim is seriously harmed. This article proposes providing multi-component treatment programs at FEP in order to prevent aggressive and antisocial behaviours of persons with schizophrenia.Non-systematic reviews of epidemiological studies of AB among persons with schizophrenia, of the defining characteristics of sub-types of persons with schizophrenia who engage in AB and their responses to treatment, and of FEP service outcomes.Studies have shown that mental health services that simultaneously target schizophrenia and aggressive behaviour are most effective both in reducing psychotic symptoms and aggressive behaviour. Evidence, although not abundant, suggests that a multi-component treatment program that would include the components recommended to treat schizophrenia and cognitive-behavioural interventions to reduce A+AB, and the other factors promoting A+AB such as substance misuse, victimisation, and poor recognition of emotions in the faces of others has the potential to effectively treat schizophrenia and reduce A+AB. Patients with a recent onset of AB would require few components of treatment, while those with prior conduct disorder would require all. Such a program of treatment would be long and intense.Trials are needed to test the effectiveness of multi-component treatment programs targeting schizophrenia and A+AB at FEP. Studies are also necessary to determine whether providing such programs in hospitals and/or prisons, with long-term community after-care, and in some cases with court orders to participate in treatment, would enhance effectiveness. Whether investing at FEP would be cost-effective requires investigation. First-episode psychosis (FEP) services have improved clinical care by intervening early in the course of illness –3. By FEMuch evidence confirms that individuals who are developing, or who present, schizophrenia are more likely than age and sex matched peers to engage in AB , 5. SomeA meta-analysis showed that 35% of individuals who contacted services for a first episode of psychosis had previously committed at least one assault , and subWhile specialized services for first episode psychosis effectively treat schizophrenia, typically they do not assess nor treat AB or antisocial behaviour –3. Yet, Overall, studies and meta-analyses show that approximately one-third of FEP patients have a history of A+AB and/or crime and thereby a very increased risk to continue to engage in A+AB and crime. Treatment focused on schizophrenia, even when the intensity is increased as in the OPUS trial , 17, 19,Among persons developing schizophrenia who offend or engage in AB prior to a first episode of psychosis are two distinct sub-groups. The largest sub-group, ~20–40% of persons with schizophrenia, present a history of conduct disorder that emerged in childhood . These iOnce psychosis onsets, patients with schizophrenia and prior conduct disorder show similar patterns of positive symptoms as other patients, but fewer negative symptoms –25. AmonX2(N = 186) = 3.99, p = 0.046]  as compared to patients with prior conduct disorder (10.4%)  , 32, in Patient self-reports using standardized, validated questionnaires, and reports by older siblings and parents identify prior conduct problems and AB , 33. OffThus, among patients presenting a FEP, two sub-groups can be identified, one with a long history of conduct problems, AB, sometimes criminal offending, and another with recent AB and sometimes violent, criminal offending. Patients in both sub-groups typically present comorbid substance use disorders.A+AB and offending persist after FEP causing further suffering to perpetrators and victims and impacting general and forensic psychiatric services and the criminal justice system. Some of those who are prosecuted are judged not criminally responsible due to a mental disorder and held within forensic psychiatric hospitals. A recent study of all persons found not criminally responsible due to a mental disorder in British Columbia, Ontario, and Quebec Canada from 2000 to 2005 found that most were men 85%) with a diagnosis of schizophrenia 71%) prosecuted for a violent crime 5% with a. The per1% prosecIn some countries a small number of persons with schizophrenia are prosecuted and sentenced to a correctional facility  see a U and in 2General psychiatric services treat many patients with schizophrenia who present A+AB. For example, a study of 205 patients with psychosis hospitalized in a general psychiatry service in a UK university hospital, found that 63.3% of the men and 23.5% of the women had been convicted for non-violent crimes, and 46.7% of the men and 16.5% of the women for violent crimes. The male offenders had been convicted, on average, for 10.7 non-violent crimes and for two violent crimes. The female offenders had been convicted, on average for 9.7 non-violent crimes, and two violent crimes. The male patients were three times more likely than men in the general UK population to be convicted of non-violent crimes and five times more likely to be convicted of violent crimes. The female patients were three times more likely than women in the UK to be convicted of non-violent crimes and 17 times for violent crimes. In similar comparisons with Swedish and Danish patient and general population samples, elevations in risk of offending among male patients were similar, while the risk of violence was higher among the female patients in the UK. In this UK sample of inpatients, 52% of the men and 31% of the women self-reported AB, and 21% of the men and 15% of the women reported AB that seriously injured another . HoweverPeople developing, and presenting, schizophrenia are more likely than their healthy peers to misuse substances . For exaFrom childhood onwards, persons with schizophrenia have problems recognizing emotions in the faces of others from childhood onwards , 45. PooAnother factor linked to AB among persons with schizophrenia is physical victimisation. Many studies show that children/adolescents developing schizophrenia are significantly more likely to experience physical and/or sexual maltreatment, and bullying than their healthy peers . Among pIn-hospital  or in-prGiven the knowledge about the timing of AB and offending among persons with schizophrenia, FEP clinics have the potential to intervene and prevent much, if not all, subsequent A+AB and offending. This would require focusing treatment on schizophrenia as well as on A+AB. Consider such a multi-component treatment program see . The resThe accumulated evidence suggests that multi-component treatment programs that are tailored to individual patient needs would last many months followed by community care that also focused on both schizophrenia and A+AB. Patients with prior conduct disorder might benefit if the program was initially offered in a hospital, or within a special unit in a correctional facility for those who have committed crimes.Encouraging patients with a history of A+AB to engage with lengthy, intensive treatment programs is a challenge. We tried and failed ! We condA research worker interviewed each of the 28 participants before treatment began, every month for the subsequent 6 months, and after the planned termination of treatment. Patients were paid £5.50 for each interview. Patients were randomly assigned to R&RP plus their usual community care or only their usual community care. Therapists contacted participants before the first R&RP session and after each missed session to encourage participation and to provide practical information. As we observed the lack of participation by patients in the RR&P, we offered two additional sessions of motivation therapy to the last 10 patients. The average time spent by therapists engaging each patient in the R&RP was 2.9 h (SD = 2.6) and the total time required for training, preparation, reminders, motivational interviews and delivery of R&RP was 372.6 h.Of the 28 patients, 25 attended no R&RP session and three attended one session. Five patients had been readmitted to hospital and were not given leave from the ward to attend, nine were too busy, four were confused or afraid of attending, and no reasons for failure to attend were provided by the others. By contrast, all participants completed a lengthy interview at study entry, and one-third to one-half completed monthly interviews for which they were paid £5.50 for each interview. During the 6 month follow-up period, according to file and/or self-reports, four (14.3%) patients were convicted of criminal offences, 16 (57.1%) were in contact with the police, 10 (35.7%) engaged in at least one physically aggressive behaviour towards another person, and nine (32.1%) experienced physical victimisation. Four (14.3%) patients reported misusing alcohol and 12 (42.9%) reported using illicit drugs. All were partially or fully compliant with meetings with their community treatment team, with an average of 12 (SD = 7.0) meetings during the follow-up period. In conclusion, patients with severe mental illness failed to attend R&RP, many completed research interviews for which they were paid, and all attended regular meetings with care co-ordinators who assured that their social benefits continued.Post-hoc analyses of completers vs. non-completers determined that programme completers showed improvements in social problem-solving at the end of treatment and changes in criminal attitudes at 12 months post-treatment, and after controlling for psychopathic traits, fewer incidents of violence, verbal aggression, and leave violations during treatment, and less verbal aggression and substance use at 12-months posttreatment (A randomized, controlled, trial focused on the R&RP among men with psychotic disorders in a forensic hospital. Only half of the patients allocated to receive R&RP completed the programme. reatment , 67. A mreatment . These rreatment .Trials are also needed to identify effective strategies for ensuring participation and completion of lengthy and intense treatment programs. Studies of forensic assertive case management, mental health courts, outpatient commitment orders, jail diversion and re-entry programs either showed a small positive effect or no effect on compliance with antipsychotic medication and A+AB and/or criminality. Most studies, however, did not take account of the treatment provided that was generally very limited [for reviews see –73]. MenAll the available evidence suggests that identifying and treating A+AB at FEP, in addition to psychosis, would reduce suffering and costs and promote independent, safe, community tenure for patients. In addition to trials to test these propositions, cost-benefit studies of intervening at FEP are needed. Funds currently spent on mental and physical care of victims, policing, courts, forensic hospitals, review boards, prisons and penitentiaries could be used to establish effective treatment programs at FEP. Suffering, stigma, and costs could also be reduced by further research and interventions aimed at early-intervention . In a meThe author confirms being the sole contributor of this work and has approved it for publication.This work was supported by the Haina Institute of Forensic Psychiatry.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In the meantime, strong within-proficiency topic effects were found on the majority of measures in the syntactic, lexical, and morphological dimensions.In studies on second language writing, linguistic complexity exhibited by learners has long been regarded as being indicative of writing proficiency. However, there are relatively scant studies focusing on the diversity and structural elaboration of complexity in L2 production data that are extracted from high-stakes tests [such as Test of English as a Foreign Language (TOEFL) and International English Language Testing System (IELTS)]. Using a large-scale learner corpus collected from a TOEFL (internet-based test (iBT), this study aims to explore the extent to which the three dimensions of linguistic complexity, syntactic, lexical, and morphological complexity, are associated with human scoring in high-stakes tests. In addition, we also tend to tap into within-genre topic effects on the production of complexity measures by learners. To this end, a total of 1,002 writing samples were collected from a TOEFL11 corpus, and six automated-coding instruments were used to investigate the variations of complexity among Chinese English as a Foreign Language (EFL) learners. The results from the correlation analysis, multiple linear regression, and independent sample  As one of the two productive skills (the other is speaking), writing constitutes an essential part of education. Among the indicators of writing quality, the presence of linguistic complexity has received extensive attention among L2 researchers and practitioners, since indices of complexity have been considered of vital importance in evaluating language production and can be used “to gauge proficiency, to describe performance, and to benchmark development” Ortega, , p.128. Test and Score Data Summary for TOEFL iBT® Test (2010–2019). Although there has been improvement in TOEFL holistic score from 77 points in 2010 to 81 points in 2019 , the average score of writing is 20 points , a score which falls within the range of High-Intermediate level (17–23) and remains unchanged over the past 10 years The global spread of English in academic contexts has led to its pervasive power over EFL/ESL education around the world. One manifestation lies in the increasing number of students who are registering for and taking international standardized tests like TOEFL and IELTS as proof of their language qualifications and as their first step to embark on adventures in education overseas. However, despite best efforts, Chinese test-takers still display poor performance in TOEFL Writing Section as evidenced by the With this in mind, our study is, therefore, aimed to extend previous studies using a large-scale learner corpus collected from TOEFL iBT to explore the variations in the production of complexity measures by learners at different human-rated writing score levels along the syntactic, lexical, and morphological dimensions, as well as the effects of topic on the selection of linguistic features. The findings will provide insights into what linguistic devices are truly predicative of and would correlate with quality writing in academic settings: a real linking of “complexity” theory with practice.via system complexity and structure complexity. System complexity deals with a lexical layer in the language system and its subsystems, engaging variables such as collocational and lexemic items; while structure complexity is composed of formal and functional complexity targeting morphological  and syntactic  properties, respectively. In this article, we adopt the definition and taxonomy proposed by Bulte and Housen  in this respect, we aim to explore the correlations between the constructs of complexity and writing scores in international standardized English proficiency assessments. As mentioned before, the production of such high-level academic tests would elicit different writing behaviors and demonstrate different language abilities among learners. In the meantime, high-stakes tests are expected to differ fundamentally from low-stakes, the ones that are administered in instructional settings, such as EAP programs, classroom practices, and writing coursework, and pose few challenges and are less difficult to students. Language learners in TOEFL-like test-driven measurement of writing proficiency are assumed to be sufficiently prepared and have given full play to the materials and writing techniques. In addition, high-stakes tests like TOEFL iBT can foster motivation and engagement of students in taking writing tasks instead of casual and careless, even unwilling, responses to fulfilling the measurement procedure imposed by researchers and practitioners. Based on the evaluative criteria for writing tasks in What features of syntactic, lexical, and morphological complexity have high predictive power and value that are directly interpretable between proficiency levels? That is, how complexity governs the use of linguistic devices in TOEFL independent writing tasks among Chinese test takers. Furthermore, is human-assigned scoring significantly and positively correlated with linguistically complex measures?How do topic-related variables affect the writing performance of test takers regarding the use of complexity at different levels and subjective evaluations by human raters?We assume that there will be clear differences between writing quality and values of complexity-related measurement in relation to the syntactic, lexical, and morphological indices. Specifically, we expect that there would be a linear correlation between the three dimensions of linguistic complexity, namely, syntactic, lexical, and morphological, and human expert scorings of Chinese EFL writings. The growth in the manipulation of linguistic features would result in high scores in essays. Our further assumption is that the written production of complexity measures by learners can be affected by topic effect since topic familiarity would play an important role in explaining variances in the human global judgment of essay quality. In other words, different topics require different reasoning and cognitive demand imposed on writers, thus leading to the variability in the use of linguistically complex structures.low (scoring between 1 and 2), medium (scoring between 2.5 and 3.5), and high (scoring between 4 and 5). This study excludes essays rated as low, as they contain “a noticeably inappropriate choice of words or word forms,” “an accumulation of errors in sentence structure and/or usage”, and “serious and frequent errors in sentence structure or usage.”low-score level, and some low-scored essays are even <50 words in length. In all, a total of 727 essay samples from the group medium and 275 from the group high across eight prompts from Chinese test takers were selected. The distributions and descriptive statistics of the selected essays are shown in Our selected corpus for this study included sample essays written by Chinese EFL learners collected from the Educational Testing Service (ETS) research report (ETS RR-13-24): TEOFL11: A Corpus of Non-Native Written English   is 0, indicating that complexity at the lexical level statistically significantly predicts human scoring. As for independent variable coefficients, three out of the five measures, namely, synonym, hypernym, and MTLD, added statistically significantly to the prediction, with p < 0.001 .Turning to lexical measures, the MLR analysis indicates that the values of R = 0.191 and R2 = 0.036, indicating a weak relationship between the predictor variables and the outcome variable. In other words, the regression model is a relatively weak predictor of the outcome (proficiency level), and 3.6% of the variance in the data can be explained by the predictor variables . As for the results of analysis of variance, F = 18.821, p < 0.001 (0), indicating that the model was a significant predictor of human evaluation of quality writing. A closer look at the values of coefficients reveals that only V100 has a significant positive weight on the performance of test-takers between proficiency levels.The results of MLR for the morphological complexity with two predictors  produced t test with 95% confidence interval was carried out to explore which measures yielded significant differences between the two unrelated subsets: group medium and group high. To avoid Type 1 error, a Bonferroni correction was applied, which resulted in corrected alpha values of 0.00625 (0.05/8 = 0.00625),0.001 (0.05/5 = 0.001), and 0.025 (0.05/2 = 0.025) for complexity measures at the syntactic, lexical, and morphological levels, respectively. Given the results of the t- test, five out of the eight syntactic measures are found to be significantly different between proficiency levels, with C/S (t(564.333) = 3.815, p = 0), DC/T (t(1000) = 2.435, p = 0.015), C/T (t(514.048) = 2.906, p = 0.004), T/S (t(639.363) = 2.346, p = 0.019), and CP/T (t(1000) = −2.372, p = 0.018). As for lexical complexity, test takers displayed significant differences across each group in use of synonym (t(1000) = −4.481, p = 0), hypernym (t(1000) = −6.104, p = 0), and MTLD (t(1000) = −5.642, p = 0), respectively, with the other two indexes (frequency and collocation) suggesting no proficiency effect on their lexis decisions. Finally, both indexes of morphological complexity were significantly different between variances of the two proficiency groups, with V100 (t(1000) = −6.078, p = 0) and T/F (t(1000) = −2.744, p = 0.006).Furthermore, an independent sample t-test, effect sizes were also calculated to determine the “size” of the differences between group means. t-test, it is clear from medium and high with regard to the use of hypernym and V100, the observed standardized mean differences were often associated with small effect sizes, representing a relatively moderate differentiation between the two groups on a given variable. It is also suggested that despite the statistically significant differences in other measures as the aforementioned in the t-test, namely, C/S, DC/T, C/T, T/S, CP/T, MTLD, synonym, V100, and T/F, such differences are indicative of trivial effect sizes that are negligible because of their very small magnitude of effect when the two groups are compared.As a complement to the post hoc analysis using Turkey HSD were performed to unveil whether there were statistically significant differences across eight topics. To examine how within-discourse-mode topics  influence the production of complexity measures by test takers at the same score level, one-way between-subjects repeated measures ANOVA tests with medium, there was a significant effect of topic on the use of complexity measures at the p < 0.05 level. Three out of the eight syntactic measures and all the five lexical and two morphological measures differed significantly across eight topics. No significant differences were found between topics regarding five syntactic measures, namely, MLC, C/S, DC/T, C/T, and T/S. Similar findings were reported from the group high, where two syntactic measures (CP/T and CN/T), four measures of lexical complexity , and two morphological measures (V100 and T/F) showed significant differences across topics. Taken together, the findings suggest that the topic does affect the ability of test-takers to select appropriate complexity measures, thus contributing to the variation and overall production of linguistic devices.As can be seen, for test-takers from the group medium correspond to 0.11, 0.057, and 0.026, respectively, suggesting a large, medium, and small effect size, respectively. While for lexical and morphological complexity, the topic was found to have a relatively large effect on the lexical use of hypernymy, frequency, and collocation , the other two lexical measures, and two morphological ones that revealed statistical significance between proficiency levels were found to statistically differ with small to medium topic effects (η2 ranging from 0.028 to 0.086). As for topic effects within the group high, the results indicated that three lexical measures out of the overall eight complexity measures that were observed to show statistically significant differences reported large effect sizes . Small to medium effects sizes were found in terms of the other five linguistic measures, namely, CP/T and CN/T for complex syntactic devices, MTLD for lexical complexity, and V100 and T/F for the complexity of morphological items, indicating that although these measures had statistical differences in proficiency, their effect sizes associated with them did not represent strong predicative strength.As for the magnitude of effects, values of eta squared of CP/T, CN/T, and VP/T in the syntactic layer from the group Furthermore, a two-way between groups ANOVA was carried out to measure whether and to what extent two main effects, i.e., proficiency and topic, would explain the variances in one interaction effect (complexity measures). *topic and the lexical production of test-takers, with a small effect size of F = 2.19, p = 0.033].As for the statistically significant effects of topic and proficiency on the output of linguistically complex measures by test takers, the results indicated that the deployment of almost all of the complexity measures was found not to be influenced by the two independent variables (proficiency and topic), with the only exception that frequency showed a significant interaction effect between proficiencyThis study aims to provide an extended account for validating complexity measures that feature prominently in studies of L2 writing. Specifically, we tapped into changes in language production in terms of the three distinct constructs of linguistic complexity among Chinese EFL learners across different topics and proficiency levels using writing samples selected from TOEFL Corpus 11, a new large-scale corpus of non-native English writing in a high-stakes English proficiency test.medium and high. This is in line with prior findings that indicated that MCI, which is geared toward measuring the variability in verbal inflection, can be indicative of the proficiency of learners , three lexical measures , and two indexes of morphological complexity (V100 and T/F), all of which appeared to serve as good indicators of EFL writing proficiency. However, most of the measures with significant differences only have small to medium size effects when the two group means (medium and high) were compared, indicating relatively moderate relationships between the structural dimensions of linguistic devices of test takers and human judgment of essay quality. In all, proficiency among Chinese EFL learners may not signal a discriminative power in their language production, and complexity in the syntactic, lexical, and morphological dimensions does not account for a major contribution to human score levels.Third, with regard to the results of the independent medium indicated that significant topic effects were observed for the majority of the complexity measures, including three out of the eight syntactic measures  and all the lexical and morphological constructs of complexity. In other words, within the same genre of argumentative writing, the values of most of the diversified forms of complexity were found to be significantly different in the group medium across eight prompts. Topic does play a role in the use of linguistic devices by test takers. Similar topic relevance was also found in the group high, with a total of eight measures displaying significant differences across topics . The results, on the one hand, further supported the findings with respect to the topic effects on the textual features of language production -related variations that would impact the presence or absence of linguistic features in essays written by learners. Our analysis revealed conflicting findings with regard to the relationships between complexity measures and writing performance judged by human raters. One manifestation lies in the only morphological index of V100 that demonstrates a positive significant correlation between the groups In addition, this study also yielded conflicting findings of topic effects. On the one hand, mediating effects from task variables (referred to as topics in this study) have been observed within the same proficiency level. On the other hand, no favorable findings have been achieved with respect to the interaction effects of a combination of both proficiency and topic on the use of structural complexity in learners' language production . This makes sense, however. Although the eight prompts fall within the same discourse mode of argumentative writing, they do differ in terms of levels of familiarity, cognitive and reasoning demand, experiences, and so on. Another factor is that the analysis is based on the between-subjects design as the TOEFL11 Corpus does not comprise essays that are written by the same test takers; a within-subjects one that is designed to balance out participant-level errors would otherwise affect the results of the current observations.This study also has implications for both EFL instructors and learners, as well as human raters. First, due attention should be paid in instructional settings concerning the association between writing quality and language production. Second, explicit and targeted teaching is of vital importance in classrooms in that the accurate output of linguistic features is contingent upon an in-depth understanding of the learnability issues in linguistic performances of students, as well as well-designed curriculum and course materials. Third, it is suggested that learners should raise their awareness of how to incorporate correct and appropriate forms of linguistic features into their academic writings, as the acquisition and development of complexity measures must take accuracy into consideration. Finally, as for human raters, the evaluation of writing quality that is heavily based on linguistic features in academic settings cannot fully represent the writing proficiency of learners. Raters should not be positively affected by the presence of complexity, since they must take into account the correct use of measures extracted from linguistic complexity. In addition, when evaluating writing responses and assigning a score, raters should adopt a holistic rating scale in a consistent manner by integrating complexity with other components of writing.It is worth noting that this study only tapped into complexity measures reflected in the corpus data of learners without taking on issues, such as grammar, accuracy, and misspelling, that may influence the results in writing assessment. It is believed that any correction or editing of these errors prior to statistical analysis would impact the perception of essay quality by human judges. It is also important to note that this study only investigated the role individual complexity dimension had played in accounting for a large proportion of scoring variances in a high-stakes test, there would be a more precise and fine-grained understanding when the three dimensions of linguistic complexity are modeled together or with another . In this regard, the results in this study may not be generalized and would invite future studies for further elaboration and new findings. As for future research in this direction, how the aforementioned two dimensions of complexity, namely, absolute and relative complexity (Bulte and Housen, The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.LQ designed the study and wrote the whole manuscript. YC edited the manuscript. YZ proofread the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.