Background: Rhythm step training (RST) for sensorimotor dual tasks is in the spotlight as it provides physical activity that is fun and allows participants to express various and creative movements, although it lacks a scientific evidence base. Therefore, this study was to investigate how RST affects the physical and cognitive functions of adolescents. Materials and Methods: A total of sixty-six female middle-schoolers were divided into non-exercise group , step training group , and rhythm step training group . To verify the combined effects of music-based rhythm and exercise, the program was conducted for 45 min/session a day, three times a week for 12 weeks. Results: RST scores increased significantly in the STG and RSTG compared to the CON after 12 weeks. Specifically, the Δ% of RST scores in the RSTG (11.44%) was higher than those of STG (9.01%) and CON (3.91%). By the end of the experiment, the power (p < 0.001), agility (p < 0.001), muscle endurance (p < 0.001), dynamic or static balance (p < 0.001), and gait velocity (p < 0.001) of RSTG were significantly improved compared to the others. The Δ% of all variables in RSTG was higher than those of the CON or STG. In addition, the verbal memory (p < 0.001) and attention (p < 0.001) of cognitive function were significantly improved in RSTG. Specifically, there was more of an increase in Δ% of RSTG for verbal memory (7.52%) and attention (10.33%) than in the CON  or STG . Conclusions: This study confirms that RST had a positive effect on the physical and cognitive functions of female middle-schoolers. We propose that rhythmic exercise combined with music is beneficial for adolescents’ physical and cognitive health. Life expectancy is increasing, in part due to the development of medical technology, although there are many other reasons behind this increase. Physical inactivity related to life expectancy is 35% in Korea due to poor lifestyle habits, so it is recommended that people increase their rate of physical activity for a healthier life . The corIn Korea, most schools have been reducing physical education hours while emphasizing the importance of other major subjects. As a result, adolescents have become accustomed to this situation and have neglected physical activity classes. The COVID-19 pandemic has further reduced the amount of time requiring physical activity . It is nMany studies have suggested that exercise combined with music can induce interest  and is sThe recently developed rhythm step training (RST) for sensorimotor dual-task training for adolescents has gained much attention as it provides physical activity with an element of fun and allows them to express various and creative thoughts during the active movement process. Previous attempts at step training without music or rhythm might have bored the adolescents as they involved repeating simple patterns without enjoyment. Improving on this, the step ladder training of RST enables the easy adjustment of the level of difficulty by changing the movement patterns. Its frequency of use is increasing day by day due to people’s favorable impression of this approach, the small space required, and the low cost. RST is an exercise program that adds upper-extremity movements to the pre-existing step training that focuses on lower-extremity movements, and it incorporates music as a continuing participation strategy . The basThis study was designed as a prospective, randomized, controlled trial to verify the effects of RST on adolescents’ physical and cognitive functions. This study measured the physical function based on power, agility, muscle endurance, static or dynamic balance, and gait ability. In addition, we measured verbal memory and attention to determine cognitive function. Before the study, the principal investigator explained all procedures to the participants and their parents or legal guardians who then read and signed a consent form. This study was conducted according to the Declaration of Helsinki (2013 version) and was approved by the Institutional Review Board of Chungnam National University (202001-SB-008-01). The 12-week experiment sought to observe the physical and cognitive functions of adolescents.The adolescents were female middle-schoolers from Daejeon, Korea. Their ages ranged from 13–16 years old. The inclusion criteria for this study were (1) voluntary participation in RST, (2) lack of regular exercise over the previous six months, and (3) no specific disease. The exclusion criteria were: having joint problems; a history of taking medication; undergoing surgery in the past six months; having depression; other mental health problems; or an intellectual disability. Initially, eighty-two girls enrolled in the study. All participants were assigned using random number tables and identification numbers on recruitment to the study. However, four adolescents were excluded due to severe obesity or having undergone a recent operation. Thus, seventy-eight participants were randomly assigned to three groups of twenty-six people each, as shown in As shown in r = 0.778 and r = 0.885, respectively, demonstrating internal consistency, and the inter-scorer reliability was r = 0.997.The RST ability was assessed using an RST evaluation scale, as shown in The physical functions were composed of power (one-leg hop test) , agilityWe assessed the cognitive function based on the verbal memory (word list memory test) and attention (trail making test) of the adolescents . First, The RST program was performed for 45 min a day, three days a week for 12 weeks, as shown in It has the following differentiation compared to the pre-existing step training: First, it is possible to increase participants’ attention and interest through rhythm change, motion transformation, and motion creation, as well as by listening to preferred music. Second, 20 basic patterns can be applied to line deformation in three stages and rhythm motion deformation in five stages. The line deformation consisted of three steps . The rhythmic motion deformation consisted of five steps . Last, the goals to be achieved can be set step-by-step, and achievement levels can be identified by a measurement scale, which can induce motivation. The intensity of all exercises was measured by ratings of perceived exertion (RPE) . For ref2) was calculated according to Cohen’s d, which is equal to the mean difference in the groups divided by the pooled SD [® 24.0 . The reliability of the RST scale was calculated as the internal consistency and inter-scorer reliability through Cronbach’s α. The normality of the study was calculated by the Shapiro–Wilk test. After primary analysis with repeated measures of ANOVA, the paired t-test was conducted to investigate the changes between pre- and post-values in each group, and Tukey’s post hoc test was implemented if there were significant differences in the time, group, and group-by-time interaction. Finally, the one-way ANOVA using GraphPad Prism 9.3.1  for delta percentage (Δ%) was conducted to compare the changes between times. The Δ% was calculated using the formula of {(postdata–predata)/predata} × 100. For all analyses, the significance level was set at p ≤ 0.05.The experiment design of this study was to analyze the group, time, and interaction by repeated measures of analysis of variance (ANOVA). Using the G*power program  , 66 subjooled SD . MicrosoAs shown in As shown in 2 = 0.034; post η2 = 0.043), agility or carioca , muscular endurance or cross over step up , dynamic balance or Tandem walk , cadence , and velocity . There were also significant differences in the time and group-by-time interaction of anterior SEBT , anterolateral SEBT , lateral SEBT , posterolateral SEBT , posterior SEBT , posteromedial SEBT , medial SEBT , and anteromedial SEBT .As shown in Although the power of CON (0.63%) and STG (1.11%) increased, that of RSTG (2.36%) increased more than the other groups, as shown in Dynamic balance decreased by −1.52% in CON and −8.20% in STG, however decreased by −9.18% in RSTG, as shown in After 12 weeks, the cadence of gait ability increased by 1.20% in CON and 0.61% in STG, however increased by 0.15% in RSTG, as shown in As shown in After 12 weeks, the Δ% of verbal memory of cognitive function increased by 3.34% in CON and 5.85% in STG, however increased by 7.52% in RSTG. As a result of the one-way analysis of variance, there was a statistically significant difference between the groups, as shown in This study found that the RST ability, power, agility, muscle endurance, balance ability, and gait ability of the rhythm step training group all significantly improved after the 12-week experiment was completed. Furthermore, it was found that verbal memory and attention of the RSTG were significantly improved after 12 weeks. Rhythm step training is an exercise program that adds upper-extremity movements to the pre-existing step training that focuses on lower-extremity movements, and it incorporates music as a continuing participation strategy . The basGenerally, power is increased through improved muscle strength. This is demonstrated when the muscle fiber momentarily contracts, based on the rate of contraction of the skeletal muscle groups . Rhythm This study also included the rhythm step training motions that require accuracy and coordination between upper and lower extremities. In addition, there were direction-changing motions such as parallel jumps and turn jumps and agility skills that require neuromuscular control and activation for proprioceptors. Through the rhythm step training of this experimental process, this study was able to assess the results of developing agility and muscular endurance, as shown in Along with an improvement of physical functions, rhythm step training may improve cognitive function by applying upper- and lower-extremity coordinating motions and creating various patterns using rhythm changes. This study observed that after 12 weeks of rhythm step training, there were significant increases in verbal memory and attention, as shown in This study found that the use of a 12-week RST program for female middle-school students improved their physical and cognitive functions. These results should raise awareness of the importance of exercise for adolescents who have difficulty participating in physical activity due to social distancing and the spread of a culture of refraining from outside activities brought on by the COVID-19 pandemic. Ultimately, rhythm step training can be used as a strategic tool to promote continuous voluntary participation in physical activities in school sports or social sports fields by utilizing appropriate music for the participants. Moreover, we found that physical activity combined with music is very important for adolescents as it improves their cognitive function.


The prevalence of colorectal cancer has remained high. Most patients have already developed into the middle and advanced stage when they are diagnosed with colorectal cancer, and a small number of them are accompanied by metastasis. In recent years, frailty has been recognized as an important factor affecting the prognosis of colorectal cancer. The aim of this study was to assess the value of frailty on prognosis in patients with colorectal cancer after treatment.We systematically searched PubMed, Embase, Web Of Science databases up until March2022. A total of 18 studies were retrieved that met the inclusion criteria, including 9 prospective studies and 9 retrospective studies. Frailty screening tools, proportion of frail patients, and outcomes of colorectal cancer patients after treatment were recorded.18 studies were included with a total of 352,535 participants. Regardless of differences in frailty screening and treatment approaches, outcomes for frailty patients were less favorable in all studies. Compared with the non-frail group, the frail group had higher mortality, more serious complications, more postoperative blood transfusions and delirium, and more support outside the home.Although there is no uniform standard for frailty screening, assessing the frailty of colorectal cancer patients is of great significance for predicting prognosis of patients after treatment. Colorectal cancer has become the third most common cancer in the world and the second most deadly cancer in the world . It mainThe PubMed, Embase, Web Of Science databases were searched to identify all studies describing frailty and colorectal cancer. The search terms used were related to the following key words: “colon”, “rectum”, “tumor”, “colorectal cancer”, “frailty”. The search string is included in detail in The range of frailty tools available to researchers and clinicians can be overwhelming. Due to the diversity of tools, we recommend choosing a frail tool for clinical or research application in cancer patients based on 1) the intent and feasibility of applying the tool to practice and 2) considering specific clinical or research needs, while also taking into account the limitations of available data. The commonly used screening tools are Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) , AmericaWe set inclusion and exclusion criteria for prospective and retrospective studies. The degree of frailty must be determined in a clinical setting, and patients were screened for frailty and divided into 2 groups. He specific inclusion and exclusion criteria are as follows.Inclusion criteria:1. Study type are Case-control studies, cohort studies, cross-sectional studies or RCT;2. Screening of frail patients applies to internationally recognized frailty screening tools;3. Divide patients into frail and non-frail groups for study;4. Primary colorectal cancer without combining other tumors;5. Full text is available, and the data is complete;5. Published publicly, excluding meeting minutes and reviews.Exclusion criteria:1. non-clinical research;2. Fail to identify or diagnose frailty;3. Patients were not divided into frail and non-frail groups for study;4. non-primary colorectal cancer or colorectal cancer combined with other types of tumors;5. The full text and complete data are not available.Two independent investigators (J.Y.P and L.J.Y) assessed the studies for eligibility, reached consensus by discussing which studies to include. When two investigators disagreed, a third investigator (C.M.H) was asked to decide on eligibility.Extracted study data by (C.M.H), including the first author, publication year, study population, study type, sample size of frail patients, frailty assessment tools, and patient quality methods.Quality assessment was done by two members of the research team (J.Y.P and L.J.Y). They assessed the quality of included studies using the Newcastle-Ottawa Cohort Study Scale. This scale was used to assess 8 questions in three domains. One point is awarded for each satisfactory answer, with a maximum of 9 points. When the score is greater than 5 points, it is considered to be eligible for inclusion. Each study was rated as low (6 points), moderate (7-8 points) or high quality (9 points). If the scores are inconsistent, they will be resolved through negotiation. The evaluation score is shown in The indicators we observed were the outcomes of colorectal cancer patients (frail and non-frail groups) after treatment. The primary outcome measure was mortality and complication rate, and the secondary outcome measures were delirium, postoperative blood transfusion, discharge destination other than home, readmission, and length of hospital stay.2 measure, with I2 >50% considered significant when P ≤ 0.10. If there was no heterogeneity , a fixed-effects model was chosen to calculate ensemble effects; otherwise, a random-effects model was used. We performed a meta-analysis of all studies, and Subgroup analyses were also performed for mortality and complication classification.We extracted data from all publications to calculate standard mean difference (SMD) and associated 95% confidence interval (CI) for continuous outcomes. P<0.05 was considered statistically significant. The presence of statistical heterogeneity of the results was assessed by using the ISTATA15.1 software was used for the standard meta−analysis and the sensitivity analysis.After initial screening of PubMed, Embase and Web Of Science databases, a total of 2373 studies were identified: 704 from Web Of Science, 701 from PubMed, and 968 from Embase. We performed title/abstract screening and full-text reading after adding constraints such as publication year, repetition, full-text reviews, and cross-references. Finally, 18 studies and 352,535 patients were included in this meta-analysis. Of the 18 studies, 9 were from Europe, 3 from North America, 5 from Asia, and 1 from Oceania. All included subjects were over 18 years old, and mainly consisted of the elderly over 65 years old. The ratio of males and females is relatively equal. The retrieval process is shown in Among the 18 studies, retrospective studies and prospective studies each accounted for 9. Mortality was assessed in 12 studies. Complications was assessed in 12 studies. Delirium was assessed in 3 studies. Postoperative blood transfusion was assessed in 3 studies. Discharge destination not home (nursing facility or other) was assessed in 4 studies. Readmission was assessed in 4 studies and hospital stay was assessed in 9 studies. Among them, mortality  and complications  =6.02 . The difference was statistically significant between the frail group and the non-frail group; The group of 90-day mortality: I-squared=51.6%, p=0.127, the heterogeneity was significant, a random effects model was adopted, RR (95%CI) =6.17 . The difference was statistically significant between the frail group and the non-frail group; The group of 1-year mortality: I-squared=85.5%, p=0, the heterogeneity was significant, a random effects model was adopted, RR (95%CI) =3.50 . The difference was statistically significant between the frail group and the non-frail group; The group of 2-year mortality: I-squared=93.3%, p=0, the heterogeneity was significant, a random effects model was adopted, RR (95% CI) =3.15 . The difference was statistically significant between the frail group and the non-frail group; The group of 5-year mortality: I-squared=92.0%, p=0, the heterogeneity was significant, a random effects model was adopted, RR (95%CI) =2.26 , The difference was statistically significant between the frail group and the non-frail group. Thus, frailty was associated with increased mortality in patients with colorectal cancer after treatment 6.A total of 7 studies involving 54,835 patients were included. Heterogeneity test was performed. The group of total complications: I-squared=22.3%, p=0.259, the heterogeneity was not significant, a fixed effects model was adopted, RR (95%CI) =1.59 . The difference was statistically significant between the frail group and the non-frail group; The group of minor complications: I-squared=78.8%, p=0.001, the heterogeneity was significant, a random effects model was adopted, RR (95%CI) =1.28 . There was no significant difference between the frail group and the non-frail group; The group of severe complications: I-squared=67.8%, p=0.008, the heterogeneity was significant, a random effects model was adopted, RR (95%CI) =2.26 . The difference was statistically significant between the frail group and the non-frail group. We found that frailty did not appear to have a significant effect on minor complications after treatment but had a significant effect on severe complications 9.A total of 3 studies involving 500 patients were included. Heterogeneity test was performed. The group of delirium: I-squared=25.5%, p=0.261, the heterogeneity was not significant, a fixed effects model was adopted, RR (95%CI) =3.08 . The difference was statistically significant between the frail group and the non-frail group. It can be discovered that frailty may be associated with high incidence of delirium  =1.87 . The difference was statistically significant between the frail group and the non-frail group. We can find that frailty may be associated with high likelihood of postoperative blood transfusion  =5.29 . The difference was statistically significant between the frail group and the non-frail group. The frail group could be found to have a higher risk of readmission  =1.90 . The difference was statistically significant between the frail group and the non-frail group. The frail group could be found to have a higher risk of readmission  =1.40 . The difference was statistically significant between the frail group and the non-frail group. The frail group could be found to have a higher risk of readmission  =3.36 )  =1.66 ) (We performed publication bias and sensitivity analyses for each outcome. Eliminating each study one by one did not change the direction of the effect size of any results, verifying that the results were stable 19.Our meta-analysis showed that frail colorectal cancer patients had poor short-term or long-term outcomes. Short-term and long-term mortality and length of hospital stay were higher in frail patients than in non-frail patients. The odds of readmission, postoperative blood transfusion, insanity, and discharge destination other than home were also higher in frail patients than in non-frail patients. In terms of complications, there was no significant difference in the probability of minor complications between the two groups. In terms of serious complications, the frail group had a higher incidence than the non-frail group. We also found that frailty has an important impact on the prognosis of patients with colorectal cancer, regardless of frailty screening tools, reported from multiple studies –26.In tests for heterogeneity, we found heterogeneity among some of the findings, especially in terms of hospital stay. Considering the interference of multiple factors such as study environment, study method, publication year, frailty screening methods, tumor location and stage, we speculate that the source of high heterogeneity may be very complex. Based on data from our research, we cannot complete the analysis of all sources of high heterogeneity. Although some studies included only colon cancer patients, some included emergency surgery in the analysis, and some had smaller sample sizes, these factors may not have had a significant effect on the overall results. It also did not show large errors in publication bias and sensitivity analysis. Overall, the studies had relatively reliable quality ratings.It has been proved that the prevalence of frailty in older patients with colorectal cancer and an indication for surgery ranges from 25 to 46 percent, depending on the population studied and the tools used to measure it . SeveralThe underlying mechanisms between frailty and poor prognosis in colorectal cancer have not been extensively studied. Nonetheless, several studies have reported elevated levels of C-reactive protein, interleukin-6, and tumor necrosis factor alpha in frail patients, suggesting that chronic inflammation may play a role , 34. ThuIn addition, factors affecting the prognosis of patients with colorectal cancer are not limited to frailty. Several studies have found that sarcopenia is also common in cancer patients and predicts longer hospital stay LOS, worse postoperative complications, susceptibility to chemotherapy toxicity, decreased quality of life, and poor survival –43. StudLikewise, malnutrition affects outcomes in patients with colorectal cancer. Preoperative malnutrition in colorectal cancer patients is associated with many adverse postoperative outcomes and poorer prognosis. Malnourished patients have significant weight loss after surgery, are more likely to develop septic shock, and have increased requirements for postoperative blood transfusion, mechanical ventilation, and reoperation . MalnutrAfter patients are discharged from the hospital, they go to many different places. We consider that those patients who recover well will go back home to live with their families because they have retained some self-care ability. Those who have lost their independence mostly go to some nursing institutions or nursing homes, and they must live with the help of others. The latter were mostly those who were identified as frail.We also found the results of postoperative blood transfusions and found that frail patients were more likely to require blood transfusions than non-frail patients. This may be due to the fact that most frail patients are already in a state of anemia, coupled with a weaker physiological reserve, which increases the difficulty of surgery and increases the risk of bleeding. After experiencing external stimuli such as surgery, it is more difficult for oneself to maintain a steady state, resulting in an external means-blood transfusion to help recovery.Notably, not all adverse outcomes were associated with preoperative frailty . We founSimilarly, frail patients with advanced tumors and preoperative bowel obstruction or perforation tend to have worse outcomes. And those who are already frail can only receive palliative chemotherapy or local surgical resection. In this palliative treatment approach, frailty is often aggravated, leading to a vicious circle with a far worse prognosis than non-frail patients. In addition, after evaluation by MNA nutritional score, Barthel index, and ASA grading standard, patients under different grades also have different prognostic performance. But no research has yet confirmed their link to frailty, and whether they should be part of frailty screening.Screening frailty as an independent risk stratification tool in colorectal cancer patients has become imperative. Standard treatment for able-bodied patients with colorectal cancer, while for frail patients with colorectal cancer, the need for an individualized treatment plan must be considered . Before A comprehensive frailty assessment of colorectal cancer patients not only facilitates the early identification and comprehensive management of frailty syndromes, but also can optimize clinical care by obtaining physical and psychological information about the patient. Future studies should evaluate the prognostic value of frailty in the diagnosis and treatment of colorectal cancer patients. Due to the increasing number of elderly CRC patients, their frailty is very common . HoweverWe searched extensively for eligible studies, but it is still possible that we missed some relevant studies in other languages or databases. In the heterogeneity test, only the length of hospital stay had a relatively large publication bias, but overall there was no obvious publication bias, and the results were relatively reliable. Also, the number of research articles we included and the sample size of the studies were not large enough. The mechanism between frailty and prognostic changes in patients with colorectal cancer is unclear. Therefore, more clinical data and mechanistic studies are needed to supplement.Frailty has a huge impact on the prognosis of colorectal cancer patients, especially in mortality and complications after treatment. To further explore how frailty alters the outcomes of colorectal cancer patients, and how to reduce the impact of this poor prognosis, more authoritative frailty assessment criteria and more clinical data are needed.The original contributions presented in the study are included in the article/MC and YH conceived and designed this study; MC completed the literature search and screening; JL and YJ included and excluded the literature and completed the quality assessment; ZG completed the data extraction; MC and ZG completed statistical analysis; MC completed the manuscript. All authors contributed to the article and approved the submitted version.The authors acknowledge Frontiers in Oncology team. They also particularly thank the reviewers and editors for their valuable comments, which helped considerably to improve the quality of the manuscript.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.


Despite the several options available for supplements containing vitamins C and E, evidence regarding the prevalence of deficiency or insufficiency of these vitamins is weak. To estimate the prevalence of deficiency or insufficiency of vitamins C and E and associated factors among women of childbearing age, in Brazil. Systematic review and meta-analysis conducted at a Brazilian public university. A search from index inception until May 2020 was conducted. Meta-analyses were performed using inverse variance for fixed models, with summary proportions calculation using Freeman-Tukey double arcsine (base case). Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. Our review identified 12 studies, comprising 1,316 participants, especially breastfeeding women. There was at least one quality weakness in all studies, mainly regarding sampling method (i.e. convenience sampling) and small sample size. The prevalence of vitamin C deficiency ranged from 0% to 40%. Only vitamin E deficiency was synthetized in meta-analyses, with mean prevalences of 6% regardless of the alpha-tocopherol cutoff in plasma, and 5% and 16% for cutoffs of < 1.6-12.0 mmol/l and < 16.2 mmol/l, respectively. The cumulative meta-analysis suggested that a trend to lower prevalence of vitamin E deficiency occurred in recent studies. Although the studies identified in this systematic review had poor methodological and reporting quality, mild-moderate vitamin C and E deficiencies were identified, especially in breastfeeding women. Thus, designing and implementing policies does not seem to be a priority, because the need has not been properly dimensioned among women of childbearing age in Brazil. CRD42020221605. They also participate in several physiological processes, such as in repairing oxidative stress, antitumor processes and hormone production.,,Vitamin C and E deficiencies have also been correlated with occurrences of scurvy, anemia, hyperbilirubinemia, tiredness and depressive conditions.,,Despite the recognized importance of these vitamins and the known risk of vitamin deficiencies, evidence among women of childbearing age is limited. The prevalence of vitamin C deficiency in adult women has been estimated to range from 6.9% in the United States to 14% in England,Studies eliciting the prevalence of a condition reflect the burden of this condition on society, and they assist in defining priorities for healthcare policies and decision-making. Well-designed cross-sectional studies are the most appropriate study design for estimating prevalence. If conducting these primary studies is not feasible, a systematic review gathering together the existing data may be the most appropriate approach for providing an idea of the magnitude of the problem and for achieving greater national representativeness.To our knowledge, no systematic review on this topic considering Brazilian data exists.The aim of this study was to estimate the prevalences of vitamins C and E deficiencies or insufficiencies and their associated factors, among women of childbearing age in Brazil.A systematic review was performed in accordance with the recommendations of the Cochrane Collaboration,Electronic searches were conducted through a pre-defined search strategy, which was described in the protocol,Studies that fulfilled the following inclusion criteria, in accordance with the CoCoPop acronym,Although cross-sectional studies are the ideal and are the study design most used for reporting prevalence, many studies have the potential to report this parameter, such as national surveys or longitudinal studies. Thus, all types of studies were included, except reviews, letters, comments, reports and case series. No language restriction was applied.Two researchers independently screened the titles and abstracts and evaluated the full-text articles. Discrepancies were resolved through consensus meetings, using another researcher as a referee. The eligibility process was conducted using spreadsheets.The following data were independently extracted by five researchers: (i) study characteristics , characteristic of the population (e.g. pregnant women), micronutrient deficiency, sampling method and funding; (ii) participants’ characteristics, i.e. ethnicity, comorbidities, drug therapy or supplement in use, body mass index (BMI), age, education and per capita income; and (iii) prevalence estimates (n/N (%)) for the total population and for subgroups when available.Given that no validated tool for assessing the risk of bias in prevalence studies exists, an assessment of the methodological and reporting quality based on the JBI Critical Appraisal Checklist for studies reporting prevalence dataAlthough no predefined cutoffs for assessing deficiencies of vitamins C and E were considered as inclusion criteria in the present review, only studies that considered the same cutoff were grouped.The data synthesis was primarily done through meta-analysis. Transitivity assessment was performed by comparing CoCoPop acronyms,Direct proportional meta-analyses were conducted using the inverse variance method (base case) and GLMM method .2) with an estimator for tauThe results from the meta-analysis were given as the proportion combined with its 95% confidence interval (CI), along with a list of the proportions (presented as percentages) with their respective 95% CI that had been found in the individual studies included in the meta-analysis. A Higgins inconsistency test  were planned for meta-analyses with at least 10 studies. Alternative statistical methods were also conducted to validate the conclusions. Potential publication bias was assessed using rank tests (base case) and linear regression or the method of moments , with at least 10 studies per meta-analysis.The data that support the findings of this study are openly available in OSF at http://doi.org/10.17605/OSF.IO/J9QMH.Our systematic review identified 1,977 records in the electronic databases after removal of duplicates  and 91 additional records identified through other sources . Through the selection process, 259 published papers were included in the systematic review regardless of the micronutrient assessed. These included 12 studies (14 papers) about vitamins C and E ,The studies were conducted between 2002 and 2017, in cities in the northeastern region (n = 8) and southeastern region (n = 4), among women who were selected mainly from maternity clinics (n = 5) and hospitals (n = 4). Only Gurgel et al.,,,,,,,,,,,A total of 1,316 participants were included, and the majority were breastfeeding , with mean ages in the different studies ranging from 16.9 to 30.0 years. Most of the studies included healthy women or excluded women with chronic or infectious diseases (n = 9), and also excluded participants using supplements containing vitamin C or E (n = 9). No study reported prevalence among non-pregnant and non-breastfeeding women. Gurgel et al.In the quality assessments, all studies presented at least one ‘No’ answer, which suggests that, overall, there was poor reporting or methodological quality. The main questions with ‘No’ answers were in relation to the following: the sampling method, since most studies used convenience samples; the sample size, due to non-reporting of a target; the description of the subjects and setting, due to absence of information on ethnicity, comorbidities, BMI, educational level or per capita income; and lack of appropriate statistical analysis, e.g. not taking into account the number of participants with events or the total number of participants observed).The response rate was considered unclear with regard to most studies assessing vitamin E and, consequently, no reliable estimate of vitamin E deficiency could be made. Considering that an adequate sample size depends on an estimate of prevalence, the estimated prevalence will directly influence the adequate response rate. For instance, if a prevalence of vitamin E deficiency of up to 6% is assumed, most of the studies achieved an adequate response rate. However, if a prevalence of at least 17% is assumed, none of the studies included presented an adequate response rate.The questions for which all the answers were ‘Yes’ were in relation to the sample frame and validity of methods used for identifying the deficiencies. A detailed assessment of the methodological quality of the studies included is presented in ,,,Only two studies (three papers) were found to report on the prevalence of deficiency or insufficiency of vitamin C.,,,,,,,,,,,Eleven studies reported on the prevalence of deficiency or insufficiency of vitamin E.Among the eleven studies, the prevalence of vitamin E deficiency ranged from 0% to 62.5%. Subgroup analyses were conducted on the mother’s weight or BMI, age, gestational weight gain, parity, delivery type, public or private maternity hospital, days after delivery, preterm or term infant, educational level, housing type  and per capita income. No statistical differences in prevalence (P < 0.05) were identified among these subgroups. No meta-analysis on these subgroup analyses was possible, either because only one study reported the subgroup or because different cutoffs were considered.In the meta-analysis for the base case, an overall prevalence of 6% (95% CI 5%-8%) was identified, while 5% (95% CI 4%-7%) and 16% (95% CI 11%-23%) were estimated for the cutoffs of 11.6-12.0 mmol/l and 16.2 mmol/l cutoffs, respectively . A cumul2 of 96%. The studies with most influence on the variations were those of de Azeredo et al.,A sensitivity analysis using the leave-one-out method was conducted but was unable to reduce the heterogeneity (89%-96%), and the overall prevalence ranged from 4% to 8% .Meta-regression analyses were conducted on publication year (P < 0.01) and cutoffs (P < 0.001), and both of these variables explained the heterogeneity . No metaIn this systematic review, twelve studies assessing the prevalence of vitamins C and E deficiency, especially among breastfeeding women, were identified. Two studies reported on vitamin C deficiency (0% to 40%) and eleven reported on vitamin E deficiency (0% to 62.5%), with a mean prevalence of 6% identified through the meta-analysis. The low frequency of assessment of vitamin C and E deficiencies in the past may explain why no systematic review reporting the prevalence of deficiency of these vitamins was found.It is likely that breastfeeding women have lower vitamin C status due to transfer of vitamin C to the growing infant via breastmilk.Furthermore, during pregnancy, placental transfer of vitamin E to the fetus is limited. Thus, breast milk is the only source of this nutrient for infants that are exclusively breastfed.Indeed, insufficient evidence of deficiencies of vitamins C and E worldwide has led to a lack of definition of what constitutes adequate intake of these micronutrients. It has also led to use of different cutoffs for defining deficiency or insufficiency. As expected, in studies evaluating alpha-tocopherol (vitamin E), the higher the cutoff point was , the greater the prevalence of deficiency also was (16%). This suggests that there is a need for studies to establish the cutoff taking into consideration the patients’ clinical and physiological conditions . It has, for instance, been found that maternal deficiency influenced the level of vitamin E in the umbilical cord, but not in the colostrum. This suggests that strategies for solving vitamin E deficiency should consider differences among pregnant and breastfeeding women.,,All the studies included here showed low reporting or methodological quality, thus producing findings with low confidence, mainly due to inappropriate sampling methods and sample sizes, which consequently did not provide representative samples of the base populations. High inconsistency was also identified, which further downgrades the confidence in the prevalence rates reported. These issues are common in observational studies.Several options for vitamin supplements containing vitamins C and E are available in Brazil, and some of them are included in the Brazilian National List of Essential Medicines (RENAME).On the other hand, little is known regarding the benefits of use of these supplements among pregnant women. A Cochrane systematic review found that routine supplementation with vitamin E in combination with other supplements, to prevent fetal death, neonatal death, premature birth, preeclampsia, premature rupture of membranes (at term or preterm) or fetal growth restriction, was not supported by the current data.,,The risk of hypervitaminosisOne limitation of this study, like in any systematic review, was that some studies may have been missed. To overcome this limitation, extensive investigation of the gray literature and manual searches to find unpublished studies were conducted, which found several studies that had not been retrieved through electronic searches. This high number of studies identified through manual search might be seen as a limitation of the search strategy. However, one hypothesis for explaining this occurrence is that the titles and abstracts of many studies may have been inadequately drafted in relation to the study subject or may not have been correctly indexed, which might have hindered retrieval. Lastly, another limitation was the absence of robust analysis on the potential factors associated with vitamin C and E deficiencies, due to poor reporting and the small size of the meta-analyses (studies and participants).Although the studies identified in this systematic review showed poor reporting and poor methodological quality, the current evidence suggests that a mild-to-moderate problem exists regarding the prevalence of deficiencies of vitamin C (ranging from 0% to 40%) and vitamin E (5% to 16%), especially among breastfeeding women and in studies in Rio Grande do Norte. Thus, it seems that designing and implementing policies to address this problem is not seen as a national priority because the deficiency problem among women of childbearing age in Brazil is not accurately represented. Future studies should consider using standard cutoffs for plasma alpha-tocopherol and ascorbic acid, random probabilistic sampling, appropriate sample sizes and predefined subgroup analyses, in order to adequately inform the prevalences of deficiencies of vitamins C and E and associated factors among women of childbearing age , and to support potential healthcare policies.


P < 0.001) and had a larger preoperative maximal aortic diameter . The intraoperative and postoperative outcomes show that the procedure times and length of hospital stay (LOS) were longer in the two-staged group. There is no significant difference in postoperative complications between the two groups. In the follow up, the freedom from re–intervention and the mean survival rate for the one-staged group were 100 vs. 100%, 92.4 vs. 95%, and 88 vs. 88% at one, two, and 5 years, respectively, whereas the mean survival rate for the two-staged group was 86.4 vs. 90.5%, 87 vs. 90.5%, and 76 vs. 84% at one, two, and 5 years, respectively, all with no statistical difference. Combined TEVAR and EVAR can be performed successfully with minimal morbidity and mortality. The one-staged repair was not associated with the increased risk for multilevel aortic pathologies treatment.Coexisting multilevel aortic pathologies were caused by atherosclerosis and hypertension and presented in a small subgroup of patients. Endovascular repair is a safe and effective treatment for a variety of aortic pathologies. However, fewer small series and cases were reported using simultaneous thoracic endovascular repair (TEVAR) and endovascular aneurysm repair (EVAR) for both aortic segments. To determine the outcomes of simultaneous and separately TEVAR and EVAR treating for multilevel aortic pathologies. Between 2010 and 2020, 31 patients and 22 patients were treated by one-staged and two-staged repair, respectively at a single center. All patients had the concomitant thoracic and abdominal aortic disease . Compared with the patients with two-staged aortic repair, the one-staged repair patients were older (mean age, 68 vs. 57 years;  Coexisting multilevel aortic pathologies are present in a small subgroup of patients, with the most frequently encountered combination being descending thoracic aortic pathologies and infrarenal abdominal aneurysms . EndovasPrevious studies have shown that one-staged intervention has been associated with higher complications such as spinal cord ischemia (SCI) . Howevern = 5), PAU (n = 21), thoracic aortic aneurysm , and AAA (n = 22). Follow-up data on outcomes of operation were collected. Mortality was assessed at in–hospital stays and postoperative 30 days.Aortic endovascular repair cases were identified in the archives of medical records of our hospital, including thoracic endovascular aortic repair (TEVAR) and abdominal aortic endovascular repair from 2010 to 2020. Multilevel aortic diseases were included in this study, including aortic dissection (AD), penetrating aortic ulcer (PAU), thoracic aortic aneurysm (TAA), and abdominal aortic aneurysm (AAA). The exclusion criteria were isolated TEVAR or endovascular aneurysm repair (EVAR), age < 18 years, and endovascular conversion to open surgery. Thirty-one were simultaneously treated with aortic stent grafts, while 22 patients were treated separately. The mean age in one-staged and two-staged groups were 68 ± 9 and 56 ± 9 years, respectively. The demographic and cardiovascular risk factors and pre-operative comorbidities are summarized in Technical success, SCI, in-hospital, and 30-day mortality were assessed as early outcomes. Survival, grafts instability, and freedom from re-intervention (FFR) were evaluated during the follow-up. The technical success was defined as endograft being deployed correctly at the planned position without iliac leg stenosis/occlusions, type I and III endoleaks, open surgical conversion, and 24 h mortality. The primary outcome was the development of postoperative SCI, which was defined according to the Society of Vascular Surgery's reporting standards .The secondary outcomes were the postoperative hospital LOS, postoperative in-hospital complications, including cardiac complications, stroke, bowel ischemia, renal failure or ischemia, and perioperative mortality. The LOS, operative time, and iodized contrast agent dosage in the two-stage groups were the accumulative amounts of two operations . CardiacThe follow-up surveillance program was done with physical examination and CTA at 2 weeks, 3 months, 6 months, and 12 months after the operation, and annually thereafter to evaluate the position of aortic grafts and endoleaks. Survival was assessed by outpatient clinic visits or telephone interviews .The patients were stratified into two groups: one-staged repair and two-staged repair. Data are present as absolute numbers and percent prevalence. Categorical variables were compared using the χThis study was approved by the Institutional Review Board at the Second Xiangya Hospital of Central South University.Demographic, cardiovascular risk factors, and pre-operative comorbidities are summarized in P < 0.001). There is no difference in the prevalence of CKD and cardiovascular and pulmonary disease risk factors, including coronary artery disease, hypertension, chronic obstructive pulmonary disease, and positive smoking history. Compared to the two-staged repair group, the one-staged group also had a larger preoperative maximal aortic diameter .Stent grafts were deployed with technical success in all patients. For one-staged repair patients, TEVAR was routinely performed prior to EVAR. For two-staged repair patients, the priority of TEVAR or EVAR was depending on what is the symptom of the aortic lesion coming first. Compared with the patients with two-staged aortic repair, the one-staged repair patients were older  and.9 ± 2.53 vs. 1.36 ± 4.1 days, respectively. Technical success was achieved in 52 cases (100%). There were two deaths, which occurred 24 h postoperatively in each group with sudden cardiac arrest. At the completion of angiography, the chimney patency was 100%. SCI occurred in two (6.5%) cases, all of them suffered transient paraparesis. Cardiac and pulmonary complications were reported in 9 and 6 cases, respectively. Cardiac complications were congestive heart failure (n = 1 vs. n = 1), new–onset arrhythmia (n = 3 vs. n = 2), and postoperative myocardial infarction (n = 2 vs. n = 2). Pulmonary complications were respiratory failure (n = 1 vs. n = 0), and pleural effusion (n = 0 vs. n = 1), and pneumonia (n = 2 vs. n = 1). Three patients suffered worsened postoperative renal function and required postoperative hemodialysis. There were two cases of bowel ischemia since the aortic dissection was affecting the superior mesenteric artery and the blood supply was from the false lumen, but the symptoms were released after absolute diet and anticoagulant treatment 2 days later. There was no postoperative stroke presented in this study.Intra- peri-, and post-operative information are summarized in p = 1). The rates of postoperative dysrhythmia, myocardial infarction, congestive heart failure, renal failure, and bowel ischemia were similar between the groups. However, the rate of postoperative LOS was less for the patients with one-staged aortic repair .No significant differences were found in the incidence of in–hospital complications between the patients with one-staged repair and two-staged repair. Specifically, each group had one patient who had postoperative SCI, but the symptom of paralysis disappeared and the strength of the lower extremity was recovered after CSF drains. The incidence of postoperative SCI was not significantly different between the two groups  have worse survival compared with the non–SCI patients, highlighting the importance of preventing this complication .Previous studies have shown that prior AAA repair is an independent risk factor for SCI after TEVAR –21. TheyTheoretically, the more extensive aortic were covered, the higher the risk of spinal cord ischemia will be. Therefore, simultaneous TEVAR and EVAR may pose a higher risk for the development of paraplegia. In the present study, there is no significance between simultaneous TEVAR and EVAR groups and one-staged group for the SCI occurrence rate. However, the patients who had developed SCI were the patients who were implanted with more aortic stent grafts, which was consistent with the previous studies. Another factor associated with SCI is hypotension, it would be a higher risk for paraplegia if the mean perioperative arterial pressure is <70 mmHg . Thus, mSome studies reported that preoperative CSF drainage may prevent SCI development. However, there is no sufficient evidence to suggest that preoperative CSF drainage is necessary for endovascular repair. Moreover, preoperative CSF drainage may cause other relative complications. Recent studies have shown that the high incidence of the drain was not obvious functional and the development of spinal hematoma resulting in permanent neurological impairment has prompted a reconsideration of routine use of this adjuvant –34.Previous studies have mentioned that the contrast load will be increased during the simultaneous repair, which is harmful to renal function and potentially causes acute renal failure postoperatively. Additionally, one-staged repairs prolong the operative time in patients who are less conditioned and have multiple comorbidities, which are all associated with long–term progressive renal decline . DespiteThe incidence of in–hospital complications was comparable between patients who underwent one-staged and two-staged repair in the overall cohort. However, despite this, the 30-day mortality was increased and the survival rate was decreased in the two-staged group, suggesting that multiple factors contribute to these outcomes. This factor can be attributed hypothetically to the patient-related factors like the patients with one-staged repair are more elderly with less conditioned and have multiple comorbidities. The ICU LOS and postoperative hospital LOS in patients with simultaneously TEVAR and EVAR were significantly shorter than the patients who underwent two-staged TEVAR and EVAR.The present study has a series of limitations. Firstly, there is a selection bias for the groups of simultaneous repair and staged repair. Secondly, based on the observational nature of the retrospective study, the present study was subject to information and missing data points and reporting bias like the data collection relying on accurate record–keeping from others. Thirdly, the study did not take into account the learning curves of different operators. Moreover, the total number of patients is relatively small in a single center with a short follow-up.In conclusion, the results from the present study have shown that simultaneous TEVAR and EVAR can be performed successfully with minimal morbidity and mortality. Although patients with one-staged repair have more risk factors for postoperative SCI, the one-staged repair was not associated with an increased risk of SCI. However, further studies to evaluate additional contributing factors to perioperative mortality in patients with multilevel aortic diseases to improve the short– and long–term outcomes were required.The data used to support the findings of this study are available from the authors upon request.The studies involving human participants were reviewed and approved by Institutional Review Board at the Second Xiangya Hospital of Central South University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.WZ and CS designed and interpreted the complete data and were major contributors to writing the manuscript. LZ and XL played a leading role in patient enrolment and conducting of the study. JQ, ML, and MW collected and analyzed the patient data regarding clinical characteristics. XL and CS supervised the study and were responsible for funding support. All authors read and approved the final manuscript.This study was supported by the National Natural Science Foundation of China (82120108005).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.


The clinical course of psychotic disorders is highly variable. Typically, researchers have captured different course types using broad pre-defined categories. However, whether these adequately capture symptom trajectories of psychotic disorders has not been fully assessed. Using data from AESOP-10, we sought to identify classes of individuals with specific symptom trajectories over a 10-year follow-up using a data-driven approach.AESOP-10 is a follow-up, at 10 years, of 532 incident cases with a first episode of psychosis initially identified in south-east London and Nottingham, UK. Using extensive information on fluctuations in the presence of psychotic symptoms, we fitted growth mixture models to identify latent trajectory classes that accounted for heterogeneity in the patterns of change in psychotic symptoms over time.We had sufficient data on psychotic symptoms during the follow-up on 326 incident patients. A four-class quadratic growth mixture model identified four trajectories of psychotic symptoms: (1) remitting-improving (58.5%); (2) late decline (5.6%); (3) late improvement (5.4%); (4) persistent (30.6%). A persistent trajectory, compared with remitting-improving, was associated with gender (more men), black Caribbean ethnicity, low baseline education and high disadvantage, low premorbid IQ, a baseline diagnosis of non-affective psychosis and long DUP. Numbers were small, but there were indications that those with a late decline trajectory more closely resembled those with a persistent trajectory.Our current approach to categorising the course of psychotic disorders may misclassify patients. This may confound efforts to elucidate the predictors of long-term course and related biomarkers. Our knowledge of the nature and predictors of the long-term course and outcomes of psychotic disorders is surprisingly limited. In a previous attempt to synthesise the evidence, we identified only 13 studies, published up to 2014, that had followed individuals with a first episode of psychosis and reported on course and outcome over a period of 8 years or more  per 100 000 person-years in London and 23.9 (95% CI 20.6–27.2) per 100 000 in Nottingham; see Kirkbride et al., Ethical approval was provided by the Joint South London and Maudsley and Institute of Psychiatry NHS Research Ethics Committee (Ref: 321/02) and the North Nottinghamshire Local Research Ethics Committee (Ref: 04/Q2402/35). The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.At baseline, detailed re-contact information was collected for all patients. At approximately 10 years, we sought to re-contact and re-interview each patient. All deaths and emigrations up to 12 December 2012 were identified through the Office for National Statistics (ONS) for England and Wales and the General Register Office (GRO) for Scotland [full details on mortality in the AESOP-10 cohort can be found in Reininghaus et al. ].At baseline, all individuals with a first-episode psychotic disorder who presented to secondary mental health services in our catchment areas over 2 years were identified from 1997 to 1999 (i.e. before early intervention services were introduced in the UK). This predates the introduction of early intervention services in the UK and all consequently received standard inpatient and community care. Data were collected on clinical presentation, sociodemographic characteristics, and a range of neurodevelopmental and social risk factors. We estimated premorbid Intelligence Quotient (IQ) using the National Adult Reading Test  using an extended version of the WHO Life Chart , compared with a model with one less class. In determining the number of classes in the final model, we also considered interpretability and class sizes  that account for heterogeneity in the patterns of change in psychotic symptoms over time  v. those not included (n = 206) are shown in online Supplementary Table S1.At baseline, we identified 532 incident cases, of whom 390 consented to complete assessments. At follow-up, of the 532 incident cases, 37 had died, 29 had emigrated and 8 were excluded. Of the remaining 458, we were able to complete a timeline of psychotic symptoms throughout the follow-up for 326 (71% of 458), with a mean length of follow-up of 10.6 years (SD 1.1). Characteristics of the included sample . This suggests the assumption that symptom data are MAR is acceptable.Overall, GMM with random intercept and slope (online Supplementary Table S4) showed a better model fit than GMM without random intercepts and slopes (online Supplementary Table S3). GMM with linear effects provided a good model fit . However, estimated means of linear time effects in these models differed markedly from observed data and model fit was further improved when adding quadratic effects of time to account for non-linear growth in the observed data, with high-quality classification of subjects into latent trajectory classes (entropy >0.90). A lower BIC value was found for GMM with quadratic effects  compared with GMM with linear effects , whereas GMM with cubic effects yielded a non-positive definite residual covariance matrix and first-order derivative product matrix even after increasing starting values and, hence, pointed to model non-identification.The BIC and Lo–Mendell–Rubin test indicated a markedly improved model fit for the quadratic GMM with two latent trajectory classes . However, there was still marked departure of observed temporal patterns of changes in psychotic symptoms from estimated means in this quadratic, two-class GMM (online Supplementary Table S5). In line with this, the BIC and bootstrapped likelihood ratio test indicated that model fit continued to improve for the 3-, 4-, 5- and 6-class quadratic GMM (online Supplementary Table S4). However, there was a lower entropy for the 5- and 6-class quadratic GMM compared with the 4-class quadratic GMM. Given also that the 5- and 6-class quadratic GMM included trajectories with <5% of subjects, the 4-class quadratic GMM was selected as the final, best-fitting model  and almost all those in the continuous  categories. A majority of those in neither category were classified in the remitting class , with the remainder spread across the other three classes  , the two largest classes captured all those in the episodic (ovement) . With res.d. 17.9) v. persistent 45.9 (s.d. 12.2); F30.0, df 3, p < 0.001]. The mean scores for the late decline  and improvement  classes were similar to that for the persistent group . On broad markers of social exclusion, over 60% of those in the remitting class were not in a long-term relationship at follow-up and over 60% were unemployed. These proportions were, not surprisingly, lower still among those in the persistent class, particularly for those employed (<10%). Even so, around 20% who were more or less continuously symptomatic were in a relationship, which underscores the importance of considering symptomatic and social outcomes separately.Further, there were strong associations between latent symptom trajectories and social outcomes . For exav. white British, Adj. OR 1.96, 95% CI 1.01–3.80), more with lower levels of education  and with higher levels of social disadvantage and isolation , more in the lowest quantile of premorbid IQ , fewer with a diagnosis of an affective psychotic disorder , and DUP was substantially longer . Not surprisingly, in the persistent class, there were more who were treatment-resistant from the outset . There was no strong evidence of differences in substance abuse or dependence among those in the persistent v. remitting class.There were several strong associations between baseline demographic, social and clinical variables, which closely mirror previous findings  had a much shorter DUP, on average, and were more likely to meet the criteria for substance abuse or dependence at some point than those in the persistent class. Second, there were some indications that those with a late decline trajectory more closely resembled those with a persistent trajectory  than did those with a late improvement trajectory (i.e. no evidence of demographic and diagnostic differences compared with remitting). Still, given the small numbers, this reading of the data is somewhat speculative and needs to be considered with caution, as the basis for hypotheses to be tested in larger samples.We sought to use a data-driven approach to identify classes of change in psychotic symptoms over time. Symptom course was highly variable. This noted, we identified four latent trajectory classes. Two were common: i.e. a trajectory characterised by remitting periods of symptoms, which became shorter and less frequent over time, leading to recovery for many (~60%), and a trajectory characterised by persistent or long periods of symptoms over the whole follow-up (~30%), with many meeting treatment-resistant criteria. For most, the pattern of course changes – and improves – over time, a finding in line with the only other attempt we are aware of to use latent class models to capture course types   and less likely to be white British. This may have introduced bias. It is possible, for example, that those who were not included may have had better outcomes, on the basis that they had fewer contacts with mental health services, which would bias our findings towards poor outcomes. Conversely, it is possible that those with negative symptoms had fewer contacts with services, which would bias our findings towards better outcomes. Second, data on the presence or absence of symptoms did not include broader measures of outcome such as social functioning, which may have yielded different trajectories as, for example, those identified by Velthorst et al.  persistent symptoms. For others, the course fluctuates. A majority tend to experience shorter and shorter episodes, a feature that is missed in the simple category of episodic. A small, but noteworthy, proportion experience marked changes in the course of symptoms over time, 3–5 years after a first episode. These groups are important because they suggest an improvement, after an initially poor course, is possible and because they point to a group of individuals who later experience long periods of psychosis, after initial short periods. These findings are likely to be intuitively valid to clinicians who regularly see patients with symptoms that wax and wane over time, and who may disengage from services at times when symptoms are absent. This highlights the need for clinical teams to regularly monitor for psychotic symptoms and the need for fluid access to, and exit from, mental health services, with re-entry to specialist services available at times when symptoms recur.To begin with, our analyses challenge our way of conceptualising course of psychotic disorders in at least three ways. First, they suggest the use of any pre-specified cut points for remission and relapse to distinguish course types is overly crude and leads to misclassification that may confound efforts to elucidate predictors of course. Second, our findings suggest the use of a middle category of neither, between episodic and continuous, is flawed and may confound findings. This is supported by our previous analyses of MRI data on a sub-sample of AESOP cases and controls using a support vector machine whole-brain classification approach to predict future illness course at the individual level . The small number in this class urges caution, but if validated in subsequent studies this has potentially important clinical implications and suggests those with, for example, a long DUP may need to be more carefully assessed and treated over time, even if the initial trajectory is positive. Further, those who improve and recover late in the course of their illness may shed light on what can be done to promote recovery when the initial course is poor. There are few clues to this in our data, because the number in this group was small, but it is an important potential avenue for future research. Particular consideration, for example, should be given to the potential impacts on improving later outcomes of clozapine, reduced substance use and greater social inclusion.Symptomatic course, following a first-episode psychosis, is heterogeneous and intrinsically difficult to predict, especially over the long-term. This poses considerable challenges for both research and clinical practice. With the advent of electronic clinical records in many services around the world and the development of statistical methods that enable more sophisticated modelling of change over time, illustrated by analyses presented in this paper, there are opportunities for a new wave of research on the course and outcome in psychotic disorders. Of particular importance, there is a substantial sub-group – as ours and other studies highlight – that experiences near persistent symptoms throughout, often despite treatment with antipsychotic medication. The associated suffering, needs and costs are hard to over-state. This underscores the importance of investment both in research and in the continued development of interventions and services to better understand, predict and support those whose symptoms persist over the long-term despite current treatment options.


The COVID-19 pandemic and its related restrictions, mainly social distancing, had an impact on the mental health of various groups, including adolescents.N = 1,786, age 15 to 19, mean age = 16.8, SD = 1.2). The data were collected online between 13 April and 24 May 2021.The main goal of our study was to explore the impact of gender, age, resilience , attachment anxiety, attachment avoidance , and mental and general health  on COVID anxiety  among a sample of Slovak adolescents (β  = 0.10) were gender , general and mental health , resilience , and attachment avoidance . Similarly, age and attachment anxiety were significant predictors with a lower effect size .Four nested linear regression models were fitted to the data and evaluated. The significant predictors that had a greater effect than our smallest effect size of interest (Our results are in line with previous research findings highlighting the importance of prevention and interventions programs focused mainly on preventing loneliness and social disconnection, fostering secure attachment with parents and peers, and increasing the resilience of adolescents, especially in the stressful time of a pandemic, to promote their mental health. Over the last 2 years, the COVID-19 pandemic has significantly affected the lives of all people, including adolescents. The restrictions associated with the pandemic, which mainly involved social distancing, had a great impact on the functioning of the school system. In many countries, including Slovakia, students in primary, secondary and higher education shifted, after sudden breaks, completely to distance learning, without the possibility of meeting their classmates and teachers. Besides education, young people also experienced other negative consequences of the pandemic, such as the financial and job instability of their families, the disruption of their general and family social relationships, acute and even chronic stress, and more.In general, stress and stressful life events are significant predictors of mental health difficulties in adolescents . AccordiAnother important factor influencing the mental health of adolescents is attachment. While insecure attachment is linked with the development of internalizing problems, anxiety, and depression in adolescents , more sePandemics may be a challenging stressor that activates the attachment system. Individuals with higher attachment anxiety may be prone to experience more health anxiety, leading to maladaptive responses to the COVID outbreak  . In an IAlthough a systematic review of longitudinal cohort studies showed that after an initial increase in mental health symptoms after the outbreak of COVID-19, there was decrease of problems comparable to pre-pandemic levels in mid-2020 among most population subgroups e.g., . From a Based on the mentioned facts about potential risk and protective factors influencing psychological adjustment to the pandemic, the main goal of present paper was to examine COVID-19 anxiety and its association with sociodemographic characteristics, mental and physical health, resilience, attachment anxiety and avoidance among adolescents in Slovakia. We hypothesized that (1) girls will have higher COVID anxiety; (2) impaired mental and physical health will be associated with higher COVID anxiety; (3) adolescents with higher attachment anxiety will have higher score in COVID anxiety; and (4) less resilient adolescents will have higher score in COVID anxiety.N = 1,184) and all the respondents were high-school students. The participants received a web link for the survey from their school management. Data collection was in line with the Declaration of Helsinki, and participation in the study was voluntary and anonymous. No incentives were offered for taking part in the survey. The study was reviewed and approved by the Scientific Ethics Committee of Palacky University Olomouc (NO 2021/11).Data was collected online from 13 April to 24 May 2021. In Slovakia, the state of emergency lasted from 1 October 2020 until 14 May 2021. Schools were in the distance learning regime, except the resumed full-time learning for the first class of primary and the last class of secondary school from 8 February 2021. Data from a total of 1786 adolescents were collected . Two-thirds (66.3%) of the research sample were females , age (continuous) and type of school where they were studying.ωtotal = 0.92 .The COVID Anxiety Scale  containsThe SF-8 Health Survey consists of 8 items, each of them representing a specific domain: (1) general health (GH), (2) physical functioning (PF), (3) role physical (RP), (4) bodily pain (BP), (5) vitality (VT), (6) social functioning (SF), (7) mental health (MH), and (8) role emotional (RE). The Slovak version of the questionnaire is similar to the Czech version , where tωtotal = 0.86 .The Brief resilience scale BRS,  consistsωtotal = 0.89 , and of the attachment avoidance it was ωtotal = 0.80 .The ECR-R questionnaire for adolescents is a self-report measure consisting of 20 items, with 10 items representing (1) attachment anxiety and (2) attachment avoidance . The iteβ = 0.10  sociodemographics – age, gender, (2) sociodemographics, resilience, (3) sociodemographics, resilience, attachment avoidance, and (4) sociodemographics, resilience, attachment avoidance, and attachment anxiety]. Each one of the 4 blocks is presented as an individual model see . The smabased on .Afterwards, the Pearson correlation coefficient was calculated to examine the relationship between general health, mental health  and COVID anxiety level. All the statistical analyses were performed in the R software, version 4.6.1 .t(10.12) = p < 0.001, Cohen’s d = 0.51]. Students attending art schools (conservatories) also reported higher mean COVID anxiety than students attending other types of high school; however, the difference was not significant. There were no significant group differences found between the counties and size of municipality either. COVID anxiety was positively correlated significantly with attachment anxiety and significantly negatively correlated with general health, mental health, and resilience (see The background characteristics of the Slovak adolescent sample are presented in ence see .β > 0.10) were all associated with a decreased level of COVID anxiety: male gender, higher general and mental health score, and higher resilience and attachment avoidance scores.The effect of the background characteristics of the participants, health, resilience and attachment anxiety and avoidance on the level of adolescent COVID anxiety was assessed using nested linear regression models. In Model 1, the background characteristics explained 6.1% of the total variance of the COVID anxiety. In this model, a higher level of the COVID anxiety was associated with female gender, higher age and students attending art schools see . After aThe main goal of this paper was to explore the relationships between COVID anxiety and its risk/protective factors. Negative predictors (protective factors) of COVID anxiety were being male, higher resilience and attachment avoidance. On the other hand, higher age, worsened general and mental health, and attachment anxiety were risk factors for COVID anxiety. The effect of other variables in the model were negligible .Mental health problems are in general more prevalent in females than in males e.g., . FemalesIn the context of the pandemic, much research has been done on both mental and physical health e.g., . ResearcResilience as the ability to bounce back from a stressful event is very important in coping with stress , especiaBased on our results, attachment anxiety is positively correlated to COVID anxiety. This result is in line with an Italian study, where the relationship between various attachment styles  and COVID anxiety was explored. Fearful and preoccupied attachment were significant positive predictors of COVID anxiety. This could be explained by the fact that people with higher attachment anxiety may tend to be more preoccupied about the pandemic and its related restrictions, which could lead to higher anxiety related to the COVID. In accordance with other research findings, attachment avoidance in our study was negatively correlated with the COVID anxiety e.g., . This reAdolescence is an especially sensitive period for brain development . Bio-psyBased on fact that in adolescence peer relationships begin to increasingly take on critical attachment functions  and the The present study has several limitations. The first regards the collected variables. The participants were not asked about any psychiatric diagnosis in their history or their mental health difficulties before the pandemic. They were also not asked if they are/were positive for COVID-19, which could have potentially affected their mental health. In both cases, the information could have helped us describe the anxiety related to COVID-19 more properly. Because our study design is cross sectional and we do not have pre-pandemic data from the same population, we cannot explore causality.The pandemic had a significant impact on various domains of life, including mental health. Our study aimed to describe anxiety specifically related to COVID-19 and its association among Slovak adolescents. Based on our results, lower resilience, higher attachment anxiety, being a girl and having a higher age are predictors related to higher COVID anxiety. As resilience is a dynamic process and not a stable trait, interventions aimed at boosting resilience and preventing loneliness and social disconnection might have significant meaning when working with adolescents (not only) in pandemic times. Moreover, fostering secure attachment with parents and peers might promote prosocial behavior and the mental health of adolescents.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 Scientific Ethics Committee of Palacky University Olomouc. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.The authors collectively conceived the main idea and design of the study. BJ and NK wrote the theoretical framework and discussion, with input from JH, GS, and JF. BJ performed the statistical analyses, with input from JF. JH, NK, and PT supervised the study. All authors contributed to the article and approved the submitted version.This study was supported by Palacky University Olomouc (project no. DSGC-2021-0122) and the Slovak Psychiatric Association (project no. 01/2021).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The reviewer FS declared a shared affiliation with the authors NK and GS to the handling editor at the time of review.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Benign prostatic hyperplasia (BPH) is the term for a type of non-malignant prostate enlargement that is most often diagnosed in men of middle age and older. Lower urinary tract symptoms (LUTS) are commonly observed in men afflicted with BPH. Evidence suggests that warm needling therapy could be applied clinically to relieve the LUTS associated with BPH, particularly in China, where experienced practitioners are readily available. In this review, the safety and effects of warm needling therapy are assessed in the context of treatment for LUTS associated with BPH.First, data for relevant randomised controlled trials and the initial periods of randomised cross-over trials will be obtained from four English databases  and six Chinese databases . The primary outcomes analysed in this protocol are improvements in urological symptoms as measured by recognized urological symptom scores, while secondary outcomes include improvement of urine flow rate measures, residual urine volume, nocturia, prostate size, and quality-of-life score. In addition, safety outcomes will be analysed by assessing incidences of adverse events. Two reviewers will independently assess and select studies, extract data and assess the risk of bias. Data synthesis and risk bias assessment will be performed with Review Manager software (version 5.3).This systematic review provides a synthesis to assess the therapeutic efficacy of warm needling therapy for LUTS associated with BPH.The present study will provide a clinically relevant evaluation of the current state of evidence regarding the therapeutic efficacy of warm needling therapy for LUTS associated with BPH.Ethical approval is not required for this review, because private information will not be collected from the included participants. The results of the study will be published in a peer-reviewed journal.PROSPERO CRD42020198360. As men age, the prevalence of LUTS increases in a closely related manner. BPH occurs most commonly in males over the age of 40. The prevalence of BPH is approximately 25% to 40% in males in their 50 s, 50% in males in their 60 s, and more than 75% in males in their 80 s.–8 Evidence suggests that the prevalence of BPH in Chinese patients is similar to that of patients in Europe and North America. A recent study reported that the prevalence of BPH was roughly 47.0% in men older than 60 who were outpatients of urology departments in China. Intriguingly, the symptoms experienced by Chinese patients afflicted with BPH tended to be more severe than those of BPH patients from the United States. Although BPH is non-carcinogenic, the condition has a profound effect on the quality of life, physical health and psychological state of patients afflicted with it. Moreover, BPH is associated with increased health care costs due to the necessity of treating the associated LUTS to restore patient health and quality of life.Benign prostatic hyperplasia (BPH) refers to the clinically relevant proliferation of smooth muscle cells and epithelial cells in the prostatic transition region, which commonly occurs in men of middle age and older. Conservative therapy, which includes watchful waiting and modification of behavior and diet, is recommended as a first treatment step for patients with mild or moderate BPH. Pharmacological therapy is recommended as a subsequent treatment step according to the characteristics of particular patients, including prostate size, level of prostate-specific antigen (PSA), and simultaneous phenomena. Unfortunately, patient compliance with regard to administration of pharmacological therapies is limited by the associated side effects and the use of drug combinations for the presence of underlying diseases. Therefore, surgical treatment is recommended for patients with poor compliance to pharmacological therapy and those with related complications.Treatments for BPH include conservative, pharmacological, and surgical therapy. To perform warm needling therapy, an acupuncture needle is warmed by placing an ignited moxa stick (composed of dried mugwort) in contact with the handle of the needle after the needle is inserted into the patient. This practice imparts acupuncture stimulation via needling, heat stimulation via infrared radiation, and pharmacological action via the use of dried mugwort.,16 Warm needling therapy combines the therapeutic effects of acupuncture and moxibustion, and it has been shown to be safe in clinical practice. The practice of warm needling therapy can be used to influence a multi-dimensional physiological network composed of the circulatory system, nervous system, endocrine system, and immune system, and thus achieve the clinical goals of maintaining physiological homeostasis and treating diseases. The benefits and safety of warm needling therapy as a treatment for LUTS associated with BPH have been explored in clinical trials, which revealed that it had a significant impact on the disease. However, the relationship between warm needling therapy and BPH has not been subjected to a comprehensive statistical analysis. Therefore, the aim of this study is to collect evidence and evaluate the effect and safety of warm needling therapy for LUTS associated with BPH.Warm needling therapy is a traditional Chinese medicinal practice that has been applied widely in China and the surrounding region for millennia.22.12.1.1Randomized controlled trials (RCTs) and the first periods of randomized cross-over trials will be included, regardless of their publication status. Duplicate publications and trials with incomparable baselines will not be subjected to analysis.2.1.2Patients with BPH diagnosed using standardized diagnostic criteria will be included in the analysis. The following individuals will be excluded from the analysis: individuals with serious neurologic, neurodegenerative, psychiatric, or systemic disorders; individuals with other diseases associated with urinary tract symptoms, including neurogenic bladder cancer and prostatic cancer; and individuals who are allergic to acupuncture or moxibustion. The enrolled participants will not be restricted with regard to ethnicity, age, or economic status.2.1.3The treatment group will include patients who underwent warm needling therapy alone or in combination with other conservative treatments, such as acupuncture, moxibustion, or pharmacological treatments. However, patients who underwent combination therapy with three or more interventions or interventions with potential safety hazards will be excluded. The control group will include patients who underwent no treatment or were placed on a waiting list, as well as those who were treated with sham warm needling or pharmacological treatments.2.1.4The primary outcome for the analysis will be changes in urological symptoms as measured by validated urological symptom scores, including but not limited to the International Prostate Symptom Score (IPSS), the American Urologic Association Symptom Score, and the Boyarsky Score.The secondary outcomes for the analysis will include improvements in urine flow rate measures, residual urine volume, nocturia, prostate size, and quality-of-life score. In addition, incidences of adverse events, including scalding, coughing, allergy, bleeding during or after needling, breaking or winding of needles, fainting, and local infection.2.2Four English databases and 6 Chinese databases will be searched for evidence dating from their inception until December 2021: MEDLINE via PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE via Elsevier, the Allied and Complementary Medicine Database (AMED) via EBSCO, China National Knowledge Infrastructure (CNKI), Wanfang Database, SinoMed, the Chinese Scientific Journal Database (VIP), the China Doctoral Dissertations Full-text Database (CDFD), and the China Master's Theses Full-text Database (CMFD). The databased will be searched using the following medical search headings (MeSH): benign prostatic hyperplasia, benign prostatic hypertrophy, warm needling, warm needle, warm acupuncture, randomised controlled trial, controlled trial, randomised, randomly, clinical trial, and comparative study. Chinese databases will be searched using translations of these search terms agreed upon by 2 independent reviewers, who will be fluent speakers of Chinese. Table 2.32.3.1Two independent reviewers, SSW and FZ, will identify and screen clinical studies for inclusion in the analysis. First, the reviewers will screen the titles and abstracts. If the reviewers cannot confirm whether or not the inclusion criteria are met by the studies based solely on the abstracts, then the full texts will be read accordingly. Any trials that meet the inclusion criteria for the analysis will be collected and cross-checked by the 2 reviewers mentioned above. A third reviewer, BL, will be included in the selection process for discussion of any dissimilarities in the pool of selected studies, after which BL will cross-check the studies in question and make a final decision regarding whether they should be included in the analysis. The study selection process is depicted in a PRISMA 2020 flow diagram in Figure 2.3.2Two independent reviewers, XD and LCJ, will extract the data from the selected studies and complete a standardized data extraction form, which will include information about the sample size, interventions, treatment frequency, treatment course, outcomes, and adverse events. XD and LCJ will cross-check the resulting dataset, after which any disagreements regarding data extraction and management will be discussed with a third reviewer, HLL, who will make a final decision on the matter.2.3.3,20 TZ and JQS will cross-check the results of the assessment, and any disagreements regarding the risk of bias assessment will be discussed with a third reviewer, BL, who will make a final decision on the matter.The risk of bias of the included studies will be assessed by 2 independent reviewers, TZ and JQS, using the “Risk of Bias” tool described in the Cochrane Handbook (version 5.1). The types of bias evaluated by the selected assessment process include selection bias , performance bias (blinding of practitioners and participants), detection bias (blinding to outcome assessment), attrition bias (incomplete datasets and participant dropout), and reporting bias (selective reporting).2.3.4Review Manager statistical software  will be used for all data analysis. A risk ratio (RR) with 95% confidence intervals (CIs) will be used for the analysis of categorical variables, whereas continuous variables will be subjected to analysis of mean difference (MD) with 95% CIs.2.3.5Before the statistical analysis, the units of the outcomes from each of the selected studies will be converted into the International System of Units.2.3.6Missing or inadequate data will be obtained from the first or corresponding author by email or telephone when it is possible to do so. Studies for which missing or inadequate data cannot be obtained will be excluded from the analysis.2.3.7I-squared (I2) statistic of homogeneity will be used to assess study heterogeneity. Studies will be determined to be unsuitable for inclusion in the analysis when the assessment of heterogeneity yields a low P value (P < .10) together with a high I2 value, which indicates significant heterogeneity.The Mantel-Haenszel chi-square test and the 2.3.8P < .10, then the data synthesis will be determined to have publication bias. In contrast, a symmetrical funnel plot indicates the presence of no publication bias.If more than 10 studies are incorporated in the data synthesis, then the reporting bias will be assessed using a funnel plot. Egger's test will be used to evaluate the funnel plots. If Egger's test indicates an asymmetrical funnel plot or 2.3.9P ≥ .1 and I2 < 50%) for the meta-analysis. A fixed-effects model will be used to analyze the results of the data synthesis. If P < .1 or I2 ≥ 50%, then the data synthesis will be performed with a random-effects model. If the meta-analysis is infeasible due to considerable methodological and clinical heterogeneity, then a narrative summary will be provided.RevMan software will be used to pool 2 or more eligible studies with low heterogeneity  guidelines. Accordingly, the quality of evidence will be assigned one of four grades: high, moderate, low, or very low.3 The results of this analysis showed that patients in the acupuncture group with moderate to severe BPH obtained statistically significant benefit in short-term follow-up endpoints. Although warm needling therapy may be assumed to represent a specific manipulation of acupuncture, the previous systematic review did not include RCTs that evaluated warm needling therapy. A preliminary search yielded more than 20 RCTs that evaluated the effects of warm needling therapy on LUTS associated with BPH. The review described here will provide a clinically relevant evaluation of the current state of evidence regarding the therapeutic efficacy of warm needling therapy for LUTS associated with BPH, which addresses the deficiencies of the previous study and may benefit patients, practitioners and policymakers.This protocol describes a systematic review and meta-analysis evaluating the effects and safety of warm needling therapy as a treatment for LUTS associated with BPH. A systematic review of acupuncture for BPH by Wei Zhang and the co-authors included data from 8 studies, which were obtained via a database search on September 1, 2016.We would like to acknowledge Dr Wei-Guang Li and Dr Hui-Chao Xu at the Department of Urology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China, who provided helpful suggestions for the review.Tao Zhang and Jing-Qing Sun formulated the study. Tao Zhang drafted the manuscript. Bin Li, Hui-Lin Liu, and Shao-Song Wang planned the search strategy. Fan Zhang, Xin Du, Wei You, and Lian-Cheng Jia reviewed the manuscript and performed revisions. The final version of the manuscript has been read and approved by all authors.Conceptualization: Tao Zhang, Jing-Qing Sun.Funding acquisition: Tao Zhang.Investigation: Fan Zhang, Xin Du, Wei You, Lian-Cheng Jia.Methodology: Bin Li, Hui-Lin Liu, Shao-Song Wang.Project administration: Tao Zhang.Supervision: Bin Li, Hui-Lin Liu, Shao-Song Wang, Jing-Qing Sun.Writing – original draft: Tao Zhang, Jing-Qing Sun.Writing – review & editing: Tao Zhang, Fan Zhang, Xin Du, Wei You, Lian-Cheng Jia, Jing-Qing Sun.