The errors in part IV of the TT presented a correlation with a forward digit span too . With respect to MoCA domains, executive functioning, and orientation were related to the TT part V errors . The orientation also correlated with the TT part III . Conclusion: Our findings show that the TT performances in patients with right hemisphere stroke and without aphasia are related to impairments in auditory–verbal span/auditory working memory mostly for TT scores on subpart V as measured by the DST and to executive function and orientation, as measured by the MoCA subtests.Background: The Token Test (TT) is widely used to examine comprehension disorders in aphasic patients, but abilities other than language may affect a patient’s performance. This study aims to explore the correlation between the TT subtest performances and the performances in extra-linguistic cognitive areas in a cohort of patients from the Intensive Rehabilitation Post-Stroke (RIPS) study with a first, right hemisphere stroke and without aphasia, prospectively enrolled at admission to intensive inpatient post-acute rehabilitation. Methods: The patients were administered the TT (50-item version), the forward and backward digit span (DST), and the Montreal Cognitive Assessment (MoCA). Spearman’s partial correlations adjusted by age were used to evaluate the association between the number of errors in the TT and the other tests’ corrected scores. Results: Of the 37 patients enrolled in this study, 29.7% made 3–11 errors on the TT, 27.0% more than 11 errors, mostly in parts IV and V. The forward and backward digit span scores showed correlations with errors in part V of the TT (r = −0.408,  The Token Test (TT) ,2,3 is wOver the past years, several versions have been proposed, that differ in the number of items, type of stimuli, type of population, and scoring modalities; a digital version is also available  and, recAlthough the TT has been specifically developed to assess auditory language comprehension, its performance involves other cognitive processes, as it often happens with neuropsychological tests. Such processes include verbal short-term memory, working memory, and inhibitory control, that is the ability to ignore distracting and competing lexical information . This isTT is included in widespread batteries for Aphasia, such as the Aachener Aphasia Test, (AAT) , originaSeveral studies have attempted to assess which functions, other than language abilities, may influence TT performance ,23,24,25Other evidence, however, does not support this relationship. For example, in a study conducted on a large sample of veterans with acquired brain lesions, Koenigs et al.  observedCognitive control has also been linked to receptive language (10) (24). In these last papers the role of inhibitory control, tested by the Stroop test, was evaluated on auditory comprehension in patients with Wernicke’s aphasia. A significant negative correlation was observed; namely, the greater the Stroop interference effect, the lower the TT performance.Based on these premises, we aimed to investigate which other components besides language comprehension may affect TT performance. To pursue this goal, we studied TT performance in stroke patients with right hemisphere lesion (RHL). Although patients with RHL may experience communicative–linguistic difficulties  study , we veriClinicalTrials.gov (Registration number: NCT03968627) and approved by each center’s local ethics committees . The study was conducted following the principles of the Declaration of Helsinki.The data analyzed in this study come from a multicenter observational prospective study, investigating the predictors of functional outcomes at discharge from inpatient post-stroke rehabilitation, the RIPS study . This stThe National Institutes of Health Stroke Scale (NIHSS) [All the people admitted to either of the four rehabilitation units from December 2019 to December 2020 were systematically assessed for eligibility and recruited upon signing informed consent. The participants meeting the following inclusion criteria were included in this study: (1) adults (aged ≥ 18 years), (2) first-ever ischemic or hemorrhagic right stroke, diagnosed clinically and with brain imaging, (3) 30 days or less from the index event, (4) first-ever admission to the rehabilitation center for the considered condition, (5) Italian mother tongue, and (6) Scoring 0 at  (NIHSS)  aphasia For this analysis, we used data from right-handed patients, with a right hemisphere lesion, for whom the TT , togetheThe NIHSS  is a widExecutive Functioning: this part is composed of three tests: (a) an alternation task adapted from the trail-making B task, (b) phonemic fluency, and (c) verbal abstraction task;Attention: this part is composed of three tests: (a) serial backward subtraction, (b) letter detection by tapping, and (c) forward/backward digit span task;Language: this part is composed of two tests: (a) naming of three images of low-familiarity animals and (b) repetition of two syntactically complex sentences;Visuospatial: this part is composed of two tests: (a) three-dimension cube copy and (b) clock drawing task;Orientation: this part is composed of one task in which the patient is asked to answer specific questions over time and place;Memory: this part is composed of a single memory test composed of delayed recall of five nouns after approximately five minutes from a learning trial.The Montreal Cognitive Assessment (MoCA) test  is a cogAccording to Italian normative data, the score should be corrected for age and education. The scores included in this study were raw scores, adjusted according to the correction grids provided in the normative data .Token Test (TT) : The verThe forward and backward digit span (FDS) test : FDS maiThe NIHSS was assessed upon admission to the rehabilitation ward, the other neuropsychological tests were performed within a week of admission.The scores corrected for age, sex, and education were used for all the following analyses. Firstly, the Shapiro–Wilk test was performed for all continuous variables to determine whether the data were normally distributed. The variables were then summarized as mean and standard deviation (SD) or median and interquartile range (IQR), according to the test results. The categorical data were presented as frequencies with percentages. To investigate whether there was an association between the number of errors performed on the TT and neuropsychological tests adjusted partial correlations were conducted. To take into account the effect of age on TT performance, age was introduced in the analyses as a confounding factor. The absolute value of the correlation coefficient (r) represents a very strong correlation if above 0.80, a strong correlation if between 0.60 and 0.79, a moderate correlation if between 0.40 and 0.59, a weak correlation if between 0.20 and 0.39, and a very weak correlation if below 0.19 .p-value < 0.05 was considered statistically significant. The analyses were carried out using the SPSS 20.0 software package .The differences between different lesion locations  were assessed using the Kruskal–Wallis test. The post hoc Bonferroni correction for multiple comparisons was applied. In all the analyses, a n = 23, 62.2%). Twenty-two participants (59.5%) had an ischemic stroke, while 15 (40.5%) had a hemorrhagic stroke. Most of the participants (n = 16) had a lobar lesion (43.2%); 37.8% (n = 14), presented a lesion in subcortical structures. There were seven (18.9%) participants with any other lesion locations. The specifics on the lesion site for individual subjects are reported in the Out of the 278 stroke patients who were eligible for the RIPS study, 235 (85%) signed the informed consent and were enrolled. Of these, 37 met the inclusion criteria and were included in this analysis. The participants had a mean age of 73.5 years . Most of the participants were male , while the lower score was recorded in the memory area .The FDS corrected score obtained by participants ranged between 3.5 and 7.9 . The lower scores were obtained in the BDS test where values ranged from 1.8 to 7.1 . A performance lower than 5% of the normative sample was observed in 10.8% of the participants for FDS (score not exceeding 4.26) and 8.1% of the participants for BDS (score not exceeding 2.65). The MoCA mean corrected score obtained by participants was 19.5 (SD: 3.8); the higher score was recorded in the The neuropsychological test scores obtained by the participants are summarized in p = 0.0013). No significant correlation was found between FDS and subparts I–III . The corrected BDS scores correlated only with the TT subpart V, . Subparts I–IV showed no significant correlation with BDS  . A correlation was also found between orientation and TT subpart III  (The significant moderate negative correlations were found between the score obtained in the = 0.002) .The TT total error distributions according to the corrected score obtained in FDS and BDS tests are presented in p = 0.485) in the number of errors according to the lesion site. Similarly, no significant difference was found in FDS (p = 0.629) and BDS (p = 0.568) corrected scores between participants with subcortical, lobar, or other lesion locations.When the association between the number of TT total errors and the lesion location was investigated, no significant differences were observed  in a group of thirty-seven patients with right hemispheric stroke and without aphasia; these were prospectively recruited within a multicentric observational study. Although it is not possible to completely exclude an influence of the right hemispheric lesions on the verbal production necessary for the execution of the neuropsychological tests, by the choice of these inclusion/exclusion criteria, we aimed at excluding a significant linguistic component to the TT performance, while taking into consideration other non-verbal cognitive aspects that could be affected by a stroke.In order to exclude aphasic patients, we decided to select right-handed patients with unilateral right brain regions. To prevent the risk of including persons with inverted cortical representation, the aphasia NIHSS score was used to exclude patients with aphasia following right hemisphere stroke. This choice was aimed at focusing on potential pathological performances in the TT, most likely unrelated to verbal comprehension problems.Our sample included patients with stroke, which occurred within 30 days before the recruitment, of either ischemic or hemorrhagic etiology, by a proportion of either in line with the literature ,43. The In our analysis, we did not observe any difference between the forward and backward span, used as measures of short-term memory and working memory, respectively. This was rather unexpected, since working memory, namely the capacity to simultaneously process verbal information, should be theoretically more related to complex sentence decoding, than the simple maintenance of linguistic information over a short period  . HoweverAmong the cognitive models of verbal short-term memory, the phonological loop integrated into the working memory model proposed by Baddeley  is probaexecutive functions and orientation, while part III also correlated with orientation. The executive functions refer to complex higher-order functions and are considered to be linked to frontal cortical–subcortical circuits. They are involved in carrying out all the more complex tasks, including attentive supervision and self-monitoring. Instead, the significant relationship between the orientation area and the more complex TT subtest could be interpreted as an effect of more severe cognitive impairment: patients who fail in orientation MoCA subtests are those with a severe cognitive impairment and that for this reason are the ones who also fail in the TT complex subtests. On the other hand, it is important to remember that MoCA is a screening test, with very short tests for each cognitive function, and for this reason it does not provide a detailed neuropsychological investigation.Concerning the analysis conducted with MoCA groupings, again part V presents a correlation with Our results suggest that the existence of an association between auditory–verbal span/auditory working memory and TT performance in right-hemisphere stroke patients. Considering that both right and left hemisphere lesions can compromise short-term and working memory ,53,54, tHowever, further considerations are necessary. Not only the cognitive functions are mutually influenced, but also the neuropsychological tests aimed at assessing one specific function are in some measure influenced by other cognitive performances. For example, the digit span includes a linguistic component and attention underlies all other cognitive functions. Each conclusion must therefore be interpreted considering the numerous factors co-involved in the phenomenon observed. Furthermore, the TT Italian normative data do not need correction for age, while in other languages, such as German, a correction for demographic information is required. This could have influenced the cut-off, which is particularly high in the Italian population, in particular for the assessment of older persons.From a pragmatic, clinical practice perspective, our results point out other factors that may affect performance at the TT. Evaluating a non-aphasic right hemisphere patient with a TT may thus reveal or confirm impairments in the short term and working memory, while, when administering a TT to an aphasic patient, we must consider that the performance could also be affected by working memory components and attention. The clinical reasoning on the pattern of errors in a TT as well as in other neuropsychological tests, and the observation and interpretation of the patient’s behavior during the test administration, may guide the examiner in the analysis of the verbal comprehension disorder and help to adequately weigh the influence of linguistic and extra-linguistic factors, respectively.This study presents several limitations. First of all, the sample size is numerically restricted. This did not allow further analyses, such as the evaluation of a possible age effect by a further division into groups. Moreover, to assess the cognitive deficits related to the TT’s performance, we used screening tests, which are not as sensitive as a complete neuropsychological evaluation. Finally, a complete and exhaustive assessment of the language skills of patients was also not performed.On the other hand, the strengths of this study lie in its prospective nature, as well as in the homogeneity of this cohort, in reference to distance from the acute event.From the clinical perspective, our results emphasize the importance to investigate verbal short-term memory when assessing and treating verbal comprehension disorders, screening for possible deficits and eventually addressing them with appropriate cognitive rehabilitation treatment. Furthermore, our results also suggest that some caution should be adopted in interpreting TT results in aphasic patients. Indeed, TT errors may not highlight an exclusive problem in linguistic decoding, so the potential effect of other extra-linguistic factors must also be taken into account. This would imply that tests that are less dependent on these highlighted cognitive factors should possibly be used to assess verbal comprehension along with the TT.In fact, the “Aachener Aphasie Test” evaluation battery , which c


Stroke is the second leading cause of death in Brazil. The social and financial burden of stroke is remarkable; however, the epidemiological profile remains poorly understood.The aim of this study was to report the incidence, lethality, and functional status at 30 and 90 days post-stroke in the cities of different Brazilian macro-regions.This is an observational, prospective, and population-based study, led in Canoas (South), Joinville , Sertãozinho (Southeast), and Sobral (Northeast) in Brazil. It was developed according to the three-step criteria recommended by the World Health Organization to conduct population-based studies on stroke. Using different sources, all hospitalized and ambulatory patients with stroke were identified and the same criteria were kept in all cities. All first events were included, regardless of sex, age, or type of stroke. Demographic and risk factor data were collected, followed by biochemical, electrocardiographic, and radiological test results. Functional status and lethality were obtained using the mRankin scale through telephonic interview .In 1 year, 932 stroke cases were registered . The incidence rates per 100,000 inhabitants, adjusted for the world population, were 63 in Canoas, 106 in Joinville, 72 in Sertãozinho, and 96 in Sobral. The majority (70.8%) were followed for 90 days. Kaplan–Meier curves showed that 90-day survival was different among cities. Sobral, which has the lowest socioeconomic indexes, revealed the worst results in terms of lethality and functional status.This study expands the knowledge of stroke epidemiology in Brazil, a middle-income country with enormous socioeconomic and cultural diversity. The discrepancy observed regarding the impact of stroke in patients from Joinville and Sobral highlights the need to improve the strategic allocation of resources to meet the health priorities in each location. Since 2005, the prevalence of stroke has increased considerably, and more than 104 million people live with its consequences worldwide .In 2018, the first Latin American Stroke Ministerial Meeting gathered the health ministries from 13 different countries in Brazil to discuss and identify ways to cooperate on reducing stroke charges in the region . Meta-reOne-third of the Latin America's population is in Brazil, where the stroke incidence per 100,000 inhabitants was reduced from 146 (95% CI: 130–163) in 1990 to 136 (95% CI: 122–153) in 2019 . The BraGiven all these worries and social inequality, yet significant in Brazil, this study aimed to report the post-stroke incidence, lethality, and functional status in different macro-regions, comparing population data from Joinville (the reference stroke center in Brazil) vs. other studied cities.The Health Ministry (HM) ordered the Brazilian Stroke Society to expand the knowledge on stroke incidence and prognosis outside the reference centers, so that the influence of socioeconomic diversity could be considered. Joinville Stroke Registry (JOINVASC) was defined as the coordinator of the study due to its population-based databank in progress since 1995, supported by municipal law since 2013 , 9. InitA JOINVASC team was sent to the selected cities to lead meetings with hospital managers and municipal health departments. Face-to-face meetings were held to train the local teams according to the three-step criteria recommended by the World Health Organization (WHO) to conduct population-based studies on stroke .This is an observational, population-based, prospective, and multicenter study. The events were registered consecutively in Sertãozinho (April 2015 to March 2016), Sobral (January to December 2015), Campo Grande (June 2015 to May 2016), Canoas (January to December 2016), and Joinville (January to December 2016), covering all seasons. The detailed methods regarding population-based studies on stroke have been previously reported , 11. StrUsing different sources, all hospitalized and ambulatory patients with stroke were identified . The samAll patients diagnosed with any type of ischemic stroke (IS), hemorrhagic stroke (HS), or subarachnoid hemorrhage (SAH) and residents in one of the studied cities, regardless of age, were included. Permanent residents who had an event outside the city limits were confirmed retrospectively and included in the study. Stroke cases who died within the first 24 h of symptom onset, without having a brain scan confirming the event, were excluded. Additionally, there were excluded patients with subdural and epidural hemorrhages, whether traumatic or not; intracerebral hemorrhages secondary to rupture of arteriovenous malformation; hemorrhages secondary to bleeding by use of oral anticoagulants or by tumor bleeding. Patients without brain images were classified as indeterminate cases and coded as IS .The at-risk population data during 2015 and 2016 were extracted from the Department of Informatics of the Unified Health System (DATASUS/MS)  classification . The assThe education level of patients was stratified on complete school years and skin color by self-definition, according to categories–black, brown, indigenous, white, and yellow – of the Brazilian Institute of Geography and Statistics (IBGE). The economic strata were based on the Brazilian Association of Research Companies classification .The Modified Rankin Scale (mRS) was used to evaluate post-stroke functional dependency and lethality, stratifying patients into three categories: independent (0–2), dependent (3–5), and dead (6) . Each nup < 0.05 considered significant. To analyze the survival rate, Kaplan–Meier curves were plotted (log-rank test). For all these analyses, the statistical software SPSS version 23.0 was used.Results of descriptive analyses are presented as average and standard deviations for quantitative variables and as frequencies, expressed in percentages, for qualitative variables. To calculate incidence and corresponding confidence intervals (CI) of 95%, the Poisson distribution was used for the number of events. The incidence specified by age and sex was adjusted by the direct method for the Brazilian population and for the WHO standard population. The incidence rates were compared using the epidemiological calculator OpenEpi , 8. For This study was approved by the Brazilian Research Ethics Commission, under opinion 759670, on 29 April 2014. The Ethics Committees from each involved city have also approved it locally. Written informed consent was obtained from all study participants or their legal representatives.n = 527), Canoas (n = 217), Sertãozinho (n = 70), and Sobral (n = 118). The city of Campo Grande (Midwest macro-region) was excluded from the intended analysis as it was not possible to achieve a significant coverage of stroke cases. The 30-day post-event follow-up was carried out in 911 cases. In 90 days, this amount was reduced to 659 cases  in Canoas; 85 (95% CI: 77.9–92.5) in Joinville; 58.7 (95% CI: 49.1–78.2) in Sertãozinho; and 77 (95% CI: 63.7–92.2) in Sobral, with no significant difference between sexes. The stroke incidence stratified by city, age group, and sex, as well as considering adjustment for the world population, is presented in n = 784) per 100,000 inhabitants, adjusted for the Brazilian population, varied significantly (p = 0.006) among participant cities, being 45 (95% CI: 37–52) in Canoas; 81 (CI 95%: 74–89) in Joinville; 44 (95% CI: 38–58) in Sertãozinho, and 60 (95% CI: 48–73) in Sobral. The detailed data regarding IS cases are shown in p < 0.001). Considering IS subtypes of defined etiology, according to the TOAST criteria, the cardioembolic subtype was significantly more common (p < 0.001) in Joinville, while the lacunar subtype was more common in Sobral (p = 0.02). Atherothrombotic stroke cases were not significantly different among participating cities. Regarding the Bamford clinical classification applied to IS cases, significant differences were identified related to the frequencies of all subtypes. Canoas reported a higher frequency of cases classified as partial anterior circulation stroke (PACS) , while Sertãozinho had the highest number of total anterior circulation strokes (TACS) . Sobral stood out for presenting the highest number of cases of lacunar stroke (LACS)  since there were no cases of posterior circulation syndrome (POCS) (p = 0.002).The incidence of IS (p = 0.003) in Canoas and Joinville. However, this difference in functional status relative to the other cities was not maintained at 90 days after the stroke (p = 0.055).The proportion of functionally independent individuals at 30 days of the IS event, evaluated by mRS, was significantly higher (p < 0.001) than observed in the reference center – Joinville (10% and 18%). However, when considering the severity of the stroke, Sobral and Sertãozinho already presented higher proportions , compared to the cities of Joinville (17.6%) and Canoas (28.3%) (p < 0.001).The lethality of IS in 30 and 90 days after event was higher in Sobral  and Sertãozinho (23% and 35%), being significantly superior (p < 0.001); however, due to the small number of cases (n = 5), such a result should be considered sparingly. The cities that presented the highest lethality rates for HS in 30 and 90 days post-event were Canoas  and Sobral (50% and 59%), surpassing the reference center – Joinville (16% and 23%), both showing significant differences (p = 0.022 and 0.005). More severe cases (NIHSS> 10) were also found mostly (p = 0.008) in Canoas (78.1%) and Sobral (70%).There were registered 105 HS cases, and the corresponding detailed data are given in p = 0.004). It has not been found that there are significant differences regarding sex, functional status, and lethality in 30 days for SAH. More details on SAH and HS are given in A total of 43 cases of SAH were registered in the four cities, with Sertãozinho standing out, where 13% of events corresponded to this type of stroke (p < 0.001). The result reinforces that Joinville, the reference center, has the best survival rate, while Sobral, the representative of the Northeast macro-region, shows the worst epidemiological situation.The Kaplan–Meier curve  shows thFor the first time, an observational study was able to analyze the incidence and lethality of stroke in medium-sized cities in three Brazilian macro-regions, prospectively and simultaneously, in addition to follow-up of the patients for 90 days to evaluate their post-event functional status. The rate of loss of patient follow-ups was similar to other studies .The demographic and socioeconomic characteristics of the population studied are in line with the findings described in several international studies, in which hospitals in low- and middle-income countries treated patients diagnosed with stroke who were, on average, younger and less educated when compared with high-income countries . A trendp = 0.006); Sobral for HS ; and Sertãozinho for SAH , as well as there were significant variations on IS subtypes. Béjot et al. (2016) analyzed contemporary European population-based records and identified huge discrepancies regarding the distribution of stroke types , and also among the ischemic subtypes , Joinville (106), Sertãozinho (72), and Sobral (96) are in line with the rates described for low- and medium-income countries (60–93), as pointed out in the publication of the “Global Burden of Disease Study 2017” .In China, a North-South gradient was identified, demonstrating a wide variation in stroke within the same country. According to the authors, their results may be related to the differences in socioeconomic conditions, knowledge of the population about the disease, and quality of primary prevention across regions . In BrazPreviously, there was a little variation in functional status from 3 months to 10 years after stroke . In BrazIn Brazil, stroke has been the main cause of death for more than 30 years. Although mortality has decreased, it is still occupying the second position, with more than 100,000 deaths per year , 36. In Stroke care in low- and middle-income countries is patchy, fragmented, and often results in poor patient outcomes . IndividThe study strengths are related to the prospective capture of all cases, following the three-step criteria proposed by WHO for population-based epidemiological studies on stroke . The stuOn the contrary, the main weakness of this study is related to the absence of equivalent data from the North and Midwest regions, thus not reflecting a comprehensive picture of the country. In addition, difficulties encountered in one or more participating cities may have impacted the results, such as data from private services; lack of complementary diagnostic tests, essential for the research purpose; short hospital stay, due to overcrowding; and lack of specialized stroke treatment units. Another example of difficulty was the temporary unavailability of CT, resulting in high rates of undetermined subtype of IS, due to incomplete investigation. Moreover, it can be assumed that there may have been underreported mild cases seen outside hospitals. Comparisons among cities regarding time to needle were not possible, despite its importance and possible influence on the results presented, since such data were not collected in all participating centers. It is also important to highlight that we had a significant loss of patient follow-up (approximately 30% after 90 days of the event), due to difficulties faced by the teams in each city. Unfortunately, these facts reflect the weaknesses of the Brazilian health system itself.It is concluded that the observed differences in the incidence and impact of stroke, among cities in different Brazilian macro-regions, are alarming, with particular prominence for the representative city of the Northeast region, where lethality was significantly higher when compared to the stroke reference center located in the South region. This epidemiological reality reflects the need for a better allocation of resources and more effective strategies for healthcare. Therefore, future studies focused on the identification and measurement of differences in access to the diagnosis and treatment of stroke are necessary to discover and possibly remedy the weak points of health assistance in the most deprived Brazilian regions.Primary data will be made available upon reasonable request.This study was approved by the Brazilian Research Ethics Commission, under opinion 759670, from April 29th, 2014. The local ethics committees from each of the participating cities also approved the study. The cities involved were Campo Grande - Federal University of Mato Grosso do Sul, Canoas - Hospital de Clínicas de Porto Alegre, Joinville - University of the Joinville Region, Sertãzinho - Hospital das Clínicas, Faculty of Medicine, University of São Paulo and Sobral - Vale do Acaraú State University. Written informed consent was obtained from all study participants or their legal representatives.NC, VN, PF, and LFe contributed to study design. VN, GWo, HP, LFu, RM-F, and GWe contributed to data collection. ES contributed to data analysis, data interpretation, and writing. NC, PF, LFe, and SM contributed to data interpretation and critical revision of the manuscript. All authors contributed to the article and approved the submitted version.This study was made possible with resources from the National Council for Scientific and Technological Development (CNPq Process: 402396/2013-8), the Brazilian Stroke Network (Rede Brasil AVC), and the Foundation for Research and Innovation Support of the State of Santa Catarina (FAPESC) which awarded a scholarship to the researcher ES.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 CS declared a shared affiliation with the author RM-F 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. 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Low back pain (LBP) causes the highest morbidity burden globally. The purpose of the present study was to project and compare the impact of three strategies for reducing the population health burden of LBP: weight loss, ergonomic interventions, and an exercise program.We have developed a microsimulation model of LBP in Canada using a new modeling platform called SimYouLate. The initial population was derived from Cycle 1 (2001) of the Canadian Community Health Survey (CCHS). We modeled an open population 20 years of age and older. Key variables included age, sex, education, body mass index (BMI), type of work, having back problems, pain level in persons with back problems, and exercise participation. The effects of interventions on the risk of LBP were obtained from the CCHS for the effect of BMI, the Global Burden of Disease Study for occupational risks, and a published meta-analysis for the effect of exercise. All interventions lasted from 2021 to 2040. The population health impact of the interventions was calculated as a difference in years lived with disability (YLDs) between the base-case scenario and each intervention scenario, and expressed as YLDs averted per intervention unit or a proportion (%) of total LBP-related YLDs.In the base-case scenario, LBP in 2020 was responsible for 424,900 YLDs in Canada and the amount increased to 460,312 YLDs in 2040. The effects of the interventions were as follows: 27,993  YLDs averted over 20 years per 0.1 unit change in log-transformed BMI (9.5% change in BMI) among individuals who were overweight and those with obesity, 19,416  YLDs per 1% reduction in the proportion of workers exposed to occupational risks, and 26,058  YLDs averted per 1% increase in the proportion of eligible patients with back problems participating in an exercise program.The study provides new data on the relationship between three types of interventions and the resultant reductions in LBP burden in Canada. According to our model, each of the interventions studied could potentially result in a substantial reduction in LBP-related disability.The online version contains supplementary material available at 10.1186/s12891-022-05747-2. Globisorders . Healthcisorders . In Canaisorders .Burden reduction strategies for LBP have evolved over the past 3 decades with a better understanding of the natural course of this condition and the effectiveness of various treatment and preventive approaches , 7. It iThe purpose of the current study was to model the population health effects of different strategies for reducing the burden of LBP. We compared the effects of primary prevention through weight reduction and ergonomic interventions in the workplace, and secondary prevention through exercise for patients with back problems. These strategies were selected because they are feasible and relatively well studied. The effect of exercise is supported by data from randomized trials, whereas evidence for weight reduction and ergonomic interventions comes primarily from epidemiological studies –3, 7–12.n = 102,761 after age restriction) and was representative of the household population of Canada [We have developed a microsimulation model of low back pain in Canada using the SimYouLate (SYL) platform described in detail in f Canada . Age/sexf Canada . Rates oThe key variables in the model were age, sex, education, BMI (from self-reported height and weight), occupation, having back problems, and pain level (0–4) in persons with back problems. Occupational group was based on the National Occupational Classification Statistics (NOC-S) 2006 at the 1-digit level . Survey We considered three interventions, a weight reduction intervention, an ergonomic intervention, and an exercise intervention  per 5 BMI units  due to LBP for the entire adult population. YLDs were calculated as prevalence of each level of pain multiplied by the appropriate disability weight . We usedThe results were expressed as total YLDs averted (counts), YLDs averted as a fraction (%) of total LBP-related YLDs, and changes in YLD rates per 1000 person-years. We compared the interventions through an equivalence plot, which shows the levels of different interventions resulting in the same numbers of YLDs averted. Equivalence values were obtained by calculating intervention levels (intensity or coverage) required to avert specified numbers of YLDs from the regression equations. For all estimates we provide 95% confidence intervals from the regression models.In the simulation model, the initial sample was 102,761 individuals. We applied survey weights to obtain the results for the population of Canada aged 20 years and older  from 2001 to 2040. In 2020, 32.8% of the simulated subjects were aged ≥ 60 years, 51.6% were females, and 52.2% had college education  as shown in Figure A2-8  as shown in Figure A2-9 . This relationship is shown in Figure A2-10 . Our open population model was well calibrated and able to accurately represent the population of Canada over time, as evidenced by relatively small differences in the distribution of demographic and clinical variables between the CCHS and SYL populations Table . In partThe majority of previous simulation modeling studies of LBP were cost-effectiveness studies. Hall et al. reviewed 21 decision-analytical studies, including several surgical treatments  and some pharmacological  and non-pharmacological  therapies for LBP and sciatica . Most ofMarkov state transition and decision tree models can be very useful, but in situations when future events may be determined by prior states or events, or the number of health states required is large, microsimulation may be a preferred approach . MicrosiOur aim was to assess the impact of preventive interventions on LBP burden in a realistic, open population over a long time horizon, and our model did not provide cost estimates. Therefore, it is generally not feasible to compare our data directly with the published cost-effectiveness studies. However, Herman et al. provided estimates of quality-adjusted live years (QALYs) gained for various non-pharmacological therapies, including exercise . It is wOur approach to evaluating population impact of interventions was to consider a wide range of intervention levels (intensity or coverage) for each intervention type rather than attempting to determine a priori what level is most feasible or realistic. Whether a particular intervention is feasible or not may depend on many factors, some of which are difficult to identify or quantify. By deriving a relationship between intervention level and its impact on YLDs we believe the results are more useful and generalizable. To facilitate policy decisions, we provide a comparison of effectiveness in terms of YLD equivalence for a wide range of levels of the interventions studied.Consider weight reduction, for example. Despite the enormous impact of the obesity epidemic, efforts to reduce obesity in Canada have not been successful. This, however, does not mean such reductions are not possible in the future, as average BMI has declined in some countries in the last decade . ExampleOur study has several limitations. First, in selecting and implementing interventions to reduce LBP and the associated disability, policymakers may need to consider the costs of interventions. Although we did not estimate costs in the current study, our data can be useful in future cost-of-illness and cost-effectiveness studies. To this end, policy experts can generate cost estimates according to intervention intensity or coverage and apply our estimates of effect. Second, we modeled LBP using self-reported data from the CCHS. While LBP is a subjective phenomenon, self-reported weight tends to be underestimated . Third, Generalizability of our results to other countries is an important question. It seems reasonable to assume that the relative risk estimates are generally applicable to most countries. We also believe that our base-case model of LBP, based on a very large, nationally representative Canadian survey, is probably generalizable to countries with a similar level of socio-demographic and economic development. Therefore, although LBP prevalence varies substantially by country, and the absolute YLDs also vary, relative measures of burden reduction are likely generalizable to high-income countries and potentially other countries as well. However, caution is needed when applying our data to low-income countries, where LBP is not as common and different burden reduction strategies may be needed .Additional file 1:Appendix 1. Technical description of SimYouLate. Appendix 2. Additional tables and figures.


There is a high incidence of maternal hypotension in spinal anesthesia for cesarean section. The aim of the study is to investigate whether there is a height-based dosing algorithm of bupivacaine that provides adequate anesthesia with less maternal hypotension.There were 2 groups of 280 parturients who did not receive prophylactic fluid preloading: Test and Conventional group. In Test group, a height based dosing algorithm was used to confirm the dose of bupivacaine in parturients without prophylactic vasopressors. In the Conventional group, a constant dose of bupivacaine was used. The complications and quality of anesthesia were evaluated.p = 0.030, 2.957 × 10−14, and 0.012). In the Test group, the incidence of hypotension, sensory block time, and number of participants with complete motor block did not change with height . The height-based dosing algorithm of bupivacaine decreased the incidence of hypotension (p = 0.004), induced lower sensory block level and less degree of motor block (p = 3.513 × 10−7 and 5.711 × 10−11). The quality of analgesia, quality of muscle relaxation, and degree of intraoperative comfort were similar in both groups .In the Conventional group, the shorter participants had higher incidence of hypotension, faster sensory block time, and more participants with complete motor block (The height influences the dose of bupivacaine in spinal anesthesia; without prophylactic fluid pre-loading and vasopressors, the height-based dosing algorithm of bupivacaine is suitable, and meets the cesarean section' requirement with less maternal hypotension.www.ClinicalTrials.gov, identifier: NCT03497364. Spinal anesthesia is popularly applied for cesarean section due to high-quality anesthesia and no inhibitory effect of general anesthetics on the fetus , 2. UnfoFor decreasing the maternal hypotension, the fluid preloading   and/or vIt is controversial whether the patient height is related to the block level for spinal anesthesia. In several studies, there is no statistical association between block level and height , 13. TheTo test our hypothesis, for cesarean section, spinal anesthesia with bupivacaine was carried out, the dose of bupivacaine was adjusted according to height in this study. In this manner, for cesarean section, we attempted to found a suitable dose of bupivacaine in spinal anesthesia.ClinicalTrials.gov on April 12, 2018 (NCT03497364). The full protocol was available in pubmed (https://www.ncbi.nlm.nih.gov/pubmed/31101694). Ethical approval for this study protocol was obtained from the Ethics Committee of Shenzhen People's Hospital of Jinan University, and this study was registered at 2 were monitored. Supplementary oxygen (2 L/min) was given via a facemask. In the forearm vein, venipuncture was carried out. Then, Ringer's lactate  was slowly infused into parturients in both groups (2 ml/kg/h).Before entering the operation room (OR), the heart rate (HR), and blood pressure of the parturients were measured. Once entering the OR, electrocardiogram, HR, blood pressure, and SPO−1.min−1  in the Conventional group  from ChaoHui drug company  was applied. The bupivacaine dose was adjusted according to the height of the parturients . Bradycardia (<60 beat/min) was treated with atropine 0.5 mg). Nausea and vomiting were treated with metoclopramide (10 mg). According to anatomical structure, for cesarean section, it is recommended that the highest sensory block level should reach dermatome level dominated by the fourth thoracic nerve (T4) . However mg. Naus2 were immediately collected. The level of sensory block was measured via hypoalgesia. If the hypoalgesia level reached T8, anesthesia was considered to be sufficient for cesarean section  were recorded. After cesarean section, the time from anesthesia initiation to skin incision, time from skin incision to delivery and operation duration were computed. The quality of analgesia (judged by the anesthetist), the quality of muscle relaxation (judged by the surgeon) and the degree of intraoperative comfort (judged by the patient via asking how you feel during operation) were recorded as excellent, good, fair, or poor .For maternal hypotension, there is an incidence of 30% in Geng et al.'s study . A ≥ 15%culation . AssuminSD). With chi-square test, the enumeration data were analyzed. With Student's t-test  or Mann-Whitney U-test/Kruskai-Wallis H , the continuous data were analyzed. A p-value <0.05 were deemed significant.Statistical analysis was performed using SPSS 13.0 software package. All continuous data were presented as the mean . The demographic data, general data, baseline data, and concomitant disease of parturients were similar in both groups .sensoryblocktoT8) was faster, and the sensory level at 10 min after anesthesia was higher in the Conventional group (completemotorblock). In comparison with both in Test groups, the Time completemotorblock was faster, and the numbers of parturients with complete motor block at 10 min after anesthesia (Number completemotorblock) were more in Conventional group (The incidence of hypotension (primary outcome), dizziness, nausea, dyspnea and bradycardia, and number of hypotensive recordings were fewer in Test group than those in Conventional groups . The incal group . For motal group .sensoryblocktoT8 and Number completemotorblock were similar in parturients with different height , a relatively small dose of bupivacaine can induce a higher sensory block level in spinal anesthesia for cesarean section . That issensoryblocktoT8 and Number completemotorblock changed with height  varying with the height (0.05 ml/2–3 cm) is a suitable algorithm; the height based dosing algorithm of bupivacaine provided sufficient anesthesia with a low incidence of hypotension in the case of no prophylactic fluid preloading and vasopressors.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics Committee of Shenzhen People's Hospital of Jinan University. The patients/participants provided their written informed consent to participate in this study.BH and ZH conceived, designed, and revised the experiments. BH, QH, CH, and ZZ performed the experiments. QH, GW, and YL analyzed the data. ZH contributed reagents, materials, and analysis tools. BH wrote the paper. All authors contributed to the article and approved the submitted version.This work was supported by grants from the Doctoral Innovation Program of Health and Family Planning Commission of Shenzhen Municipality of China (SZBC2017016) to BH.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.


Both cross-sectional and longitudinal studies demonstrated serious risk of bias with the addition of serious inconsistency of findings from cross-sectional studies. The existing literature is equivocal in terms of making a definitive judgment on the association between video game participation and loneliness. PROSPERO registration number: CRD42021283025.The purpose of this systematic review was to evaluate the existing evidence in literature addressing the relationship between video game participation and loneliness. The following databases were searched on October 2, 2021: Medline, Psychinfo, SportDiscus, Web of Science, and CINAHL. The risk of bias of cross-sectional study was assessed by using the Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross-sectional studies with attrition bias added for longitudinal studies. The results of all included studies were synthesized using narrative synthesis. Meta-analysis was utilized to synthesis the findings of the studies that had sufficient degree of statistical and methodological homogeneity. Eighteen studies were included in this systematic review, which comprised of 20,372 participants. The narrative synthesis showed mixed findings on the relationship between video game participation and loneliness. Meta-analysis that was conducted to nine cross-sectional studies revealed that video game participation was positively and weakly associated with loneliness (Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021283025. Due to the increased accessibility of personal computers, video game (VG) playing has risen to prominence as one of the most popular recreational activities worldwide in recent years. According to Newzoo, there are approximately three billion video gamers worldwide in 2021 . HoweverLoneliness is defined as an internal unpleasant state which arises from the perception of a lack of desired interpersonal relationships . LonelinThe Basic Psychological Needs (BPN) theory postulates that humans are intrinsically prone to psychological growth and integration , 16. ThiStress is a negative affective state related with the believed inability to overcome adversity . Coping Social presence (SP) was originally defined as “the degree of salience of the other person in the interaction and the consequent salience of the interpersonal relationships” .via the copresence, psychological involvement, and behavioral engagement mechanism. This sense of presence will likely to be converted into a resource that satisfies the sense of relatedness and alleviates loneliness.Co-presence refers to “the degree to which the observer believes he/she is not alone and secluded, their level of peripheral or focal awareness of the other, and their sense of the degree to which the other is peripherally or focally aware of them” , p. 247]724), p. Though many prior researchers have studied the association between loneliness and VG participation, there has been no systematic review in this field. A systematic review enables researchers to evaluate and synthesize all available evidence on a certain topic . One notThe present study was pre-registered on the International Prospective Register of Systematic Reviews . The present study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines . The PoNo restrictions were put on the population, comparison, and study design. Exergames, including virtual reality (VR) games, were omitted from this study since playing them may result in an increased amount of SP as compared to traditional VGs . The outA search of titles, abstracts, and key words was conducted on October 2, 2021 for the following five databases: Medline, Psychinfo, SportDiscus, Web of Science, and CINAHL. No restrictions were placed on publication date. Additional studies that met the inclusion criteria were identified by searching reference lists.Search parameters (key words) were developed based on the practice of previous studies , 32. In via discussion. Titles and abstracts were screened against the eligibility criteria, followed by retrieving the full texts of potentially eligible articles. The retrieved full articles were scrutinized to determine their suitability for inclusion. When full texts were not available, the articles were requested from the author via email.Results of the search were imported into Zotero (version 5.0) where duplicates were removed. The screening procedure was done by the primary investigator and confirmed by one of the co-authors. Consensus was established Data extraction form was created in Microsoft Excel. The extraction process was completed by the primary investigator and checked for accuracy by one of the co-authors. The following information was extracted from each article: author, publication year, study design, country, participant characteristics, sample size, loneliness measure, VG participation measure, game name, effect size indicators (when applicable).The risk of bias of cross-sectional studies was evaluated by using the Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross-sectional studies . This toThe Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework  was usedI2 was used to assess the heterogeneity of effect size across studies. The I2 value higher than 50% indicates a substantial heterogeneity across studies , China (n = 3), Netherlands (n = 3), South Korea (n = 2), Sweden (n = 1), Canada (n = 1), Finland (n = 1), Norway (n = 1), Germany (n = 1), Spain (n = 1), and a global study (n = 1). The sample size ranged from 151 to 5,000. One study did not specify the exact number of participants , females accounted for 25.59% of the total participants , and 0.17% (n = 34) of the participants did not declare gender information. While 16 studies employed a cross-sectional methodology, two studies used longitudinal panel design. The characteristics of each study were summarized in The 18 articles included 20,372 participants from a variety of countries, including the United States (icipants . While mn = 15) to high (n = 3). Krippendorff's α was 0.83. The primary grounds for rating the studies as having a fair risk of bias were: (1) the majority of studies, with the exception of two  onen of two ; (3) onen of two . Cronbacn of two . Table 2Of the 16 cross-sectional studies, six studies found a significant and positive relationship between VG participation and loneliness , 51, 53.Seven studies did not find a significant relationship between VG participation and loneliness , 54, 55.Three studies found mixed results on the relationship between VG participation and loneliness , 48, 56.Among the two longitudinal studies, Kowert et al.  found thMeta-analysis was conducted to nine cross-sectional studies that used similar measurement of VG participation and loneliness and consistently used Pearson's r as the effect size indicator. The reasons for the exclusion from the meta-analysis of the other seven cross-sectional studies were: (1) one study recoded loneliness into relatedness ; (2) oner = 0.10, 95% CI = 0.03–0.17, 95%PI = −0.11 to 0.30]. The forest plot in r) and 95% CI for each study, as well as the overall effect size estimated using the random effects model. The estimated between-study heterogeneity was τ2 = 0.007 (95% CI = 0.003–0.034), with an I2 value of 85.4% (95% CI = 74.2–91.8%). Despite the high degree of heterogeneity in effect sizes among studies, no study was detected as an outlier, as the 95% CI for all studies overlapped with the 95% CI of the overall estimated effect size.Through the meta-analysis, VG participation was found to be positively and weakly associated with loneliness . The trim-and-fill approach resulted in a point estimate of r = 0.148 (95% CI = 0.068–0.225). Taken together, these analyses revealed no indication of considerable publication bias.Publication bias test was done for all the studies included in the meta-analysis. The funnel plot in The quality of evidence was presented in This systematic review aimed to evaluate the relationship between VG participation and loneliness. Results from 18 studies were combined with meta-analysis being done for nine of them that used similar methodological approaches and measurement tools. The included studies represented 20,372 participants from 10 countries. The meta-analysis found that VG participation was positively and weakly associated with loneliness. The results of narrative synthesis revealed mixed findings on the relationship between VG participation and loneliness. Among cross-sectional studies, six studies found positive relationship, seven studies did not, and three studies found mixed relationship. The two longitudinal studies found that neither VG participation nor loneliness predicted each other 6 months later or 1-year later. The quality of evidence was rated very low for both cross-sectional and longitudinal studies. Overall, current literature base provides insufficient evidence to determine the relationship between VG participation and loneliness.Tying back to the theoretical framework, individuals may choose to participate in VG to cope with loneliness, which provides them the sense of SP that can be converted into a resource that satisfies the relatedness tendency and reduces the feeling of loneliness. However, none of the studies included in this review found a negative relationship between VG participation and loneliness. The results from the meta-analysis even found a positive relationship. One possible explanation is that while video gaming provides opportunities for the players to interact with others who they usually do not know, high involvement in gaming reduces their time spent with significant others in real life, which may in turn increase their sense of loneliness as previous studies suggested . AccordiIt is worth noting that in cross-sectional studies, the age of participants may be a significant factor in determining the association between VG participation and loneliness. Studies that recruited participants from universities or with an average age of over 18 years discovered a significant relationship between VG participation and loneliness , 49, 51,Although no study included in this systematic review examined the potential moderating effect of gender on the relationship between VG participation and loneliness, a substantial number of studies have revealed a gender difference in terms of loneliness, with males generally perceiving less loneliness than females , 50, 57.The high heterogeneity in both meta-analysis and narrative synthesis across study findings is less likely because of the difference in measurement tools given the consistency in the loneliness and VG participation measurement. Rather, it is probably the result of less control of confounding variables. When separating passion into harmonious passion  and obsessive passion [preoccupation and inflexible persistence toward the cherished activity ], MandryA study found that WoW players felt more lonely in real world than in online world . It is pSeveral recommendations can be proposed in light of the findings of this systematic review. To begin, as none of the studies included in this systematic review discovered a negative association between VG participation and loneliness, practitioners and video game players should exercise caution when utilizing VGs to alleviate gamer's loneliness. Secondly, as loneliness has a variety of negative repercussions –14 and tn < 10, (First, a typical concern with systematic reviews is that the evidence synthesis is only as good as the articles included. The major limitation of this review is the very low quality of evidence on the relationship between VG participation and loneliness . Second,n < 10, ], sub-grThis systematic review quantitatively and qualitatively synthesized the available evidence in the literature on the relationship between VG participation and loneliness. Given the inconsistency of the empirical results and the negative impacts of loneliness on well-being, more study in this area is strongly urged. To overcome the limitations existed in previous studies, several considerations are recommended. First, the potential causal association between VG participation and loneliness is unknown given to a dearth of experimental investigations in this field of research. Experimental evidence, particularly randomized controlled trials, would aid in our understanding of the possible causal association between VG and loneliness. Second, existing longitudinal studies used extended time intervals to examine the relationship between VG participation and loneliness. It is likely that individuals may have a brief time of increased loneliness following games and then return to their normal degree of loneliness. In future research, novel approaches such as ambulatory evaluation  may be eThe present study provides a systematic review on the relationship between VG participation and loneliness. The findings of narrative synthesis are inconclusive in terms of reaching a final conclusion on the relationship between VG participation and loneliness, despite a positive and weak relationship found in the meta-analysis. Overall, previous studies have very low quality of evidence. Additional studies are required to offer evidence for practitioners and policymakers in this area of research.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.YL, TF, and DS contributed to conception of the study. YL, JM, and JX organized the database and selected appropriate articles. YL performed the statistical analysis and wrote the first draft of the manuscript. YL, MM, TF, and DS contributed to manuscript revision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The present study aimed to explore the relationship between balance ability and all-cause death in middle-aged and elderly people and to provide a basis for formulating a balanced training plan for middle-aged and older people in China.Based on data from the China Health and Retirement Longitudinal Study (CHARLS) carried out in the years 2011, 2013, 2015, and 2018, 18,888 participants aged 45 years and above were included. Cox proportional hazard models were designed to evaluate the effect of balance ability on death events.HR = 0.90,95% CI: 0.85–0.95) for every second increase in balance ability. With balance ability <10 s as the reference group, the adjusted HRs were 0.61 (0.44–0.85) among middle-aged and elderly people. The death density of balance ability of <10 s was 73.87 per thousand person-years higher than that of ≥10 s. There was no interaction between balance ability and chronic disease, overweight, and obesity (P > 0.05).The present study found that there was an association between balance ability and death among middle-aged and older people. Multivariate Cox proportional hazard regression model analysis showed that the risk of death decreased by 10% (The risk of all-cause death in middle-aged and older people increased with the decrease in balance ability and showed no statistical significance between chronic disease, overweight, and obesity, as corroborated by the present study. Balance ability is a complex body function that is coordinated by multiple systems, and the peak value decreases with age in adults . A varieThe Ethical Review Committee at Peking University (IRB 00001052-11014) approved CHARLS for the biomarker sample collection.n = 1,597). Participants who did not have balance ability measures  for that year were excluded, resulting in a final sample size of 19,390 participants. Additionally, participants who did not have body mass index (BMI) measures were excluded (n = 512).This study includes 24,805 participants who were 45 years of age and above as per the CHARLS of 2011–2018. In Interviewers measured balance ability, which refers to the number of seconds in which a participant can semi-tandem stand for 10 s without moving or holding anything. If the participant could semi-tandem stand for 10 s, then 10 s was recorded , 16. OthThe death information for each participant and the outcome variable were obtained from death registration and certification by asking their relatives or community managers in 2013, 2015, and 2018, or at the end of follow-up . Death events were identified as “1” and survival and censorship as “0.” The survival time was calculated according to the outcome .hukou, and education. Education is classified into five categories . The term hukou includes agricultural hukou and non-agricultural hukou. Health-related factors include self-reported smoking, drinking alcohol , self-reported diseases , activities of daily living (AOLs) / instrumental activities of daily living (ADLs/IADLs), and body mass index (BMI).According to our conceptual framework, low socioeconomic position and health status are strong determinants of all-cause death. Sociodemographic status includes age, gender, marital status, 2 test), analysis of variance (ANOVA), or Mann–Whitney U-test as appropriate. Assuming missing at random, incomplete observations were imputed with multivariate imputation via classification or regression trees. Ten imputed data sets were generated and pooled using R 4.2.1.For summary statistics, the present study employed means and standard deviation (SDs) to describe continuous variables conforming to the hypothesis of normal distribution. Categorical variables were described by the frequency with percentage. Based on the baseline characteristics of balance ability, we deemed the chi-square (χHRs) with 95% confidence intervals (CIs). The risk of death was calculated based on a specific balance. Three models were designed and compared for middle-aged and elderly people. Model 1 was adjusted for age and gender. Model 2 is based on Model 1 with supplementary adjustment of marital status, household registration, education, smoking, drinking, and BMI. All covariates (15 covariables) were included in Model 3. Chronic disease status and overweight and obesity were analyzed interactively between balance ability and death to study their effects. An interaction analysis was performed to examine the potential association between balance ability and death and to determine whether the results were regulated by chronic diseases, overweight, and obesity. Finally, we performed the sensitivity analysis by repeating all analyses using an original data set without multiple interpolations.To examine the association between balance ability and death events of all causes, Cox proportional hazards models were used to calculate hazard ratios  for every second increase in balance ability. After adjusting for confounding factors, the risk of death in middle-aged and older people with balance ability ≥10 s was reduced by 40% . The death density of middle-aged and older people with a balance ability of <10 s was 73.87 per thousand person-years higher than those ≥10 s .HR = 0.84,95% CI: 0.76–0.92; HR = 0.93, 95% CI: 0.86–0.99). For those persons with the balance ability <10 s as the control group, the risk of death of ≥10 s decreased by 55 and 35% in the overweight and obese and the non-overweight and obese, respectively . There was no interaction between overweight and obesity and continuous balance ability , as well as binary balance ability   .HR = 0.88,95% CI: 0.82–0.94). For those people with a balance ability <10 s as the control group, the risk of death in the chronic disease group was reduced by 45% . There was no statistical significance in the predictive effect of continuous balance ability and binary variables on the survival of the non-chronic disease group . There was no interaction between chronic disease and continuous balance ability , as well as binary balance ability   .Sensitivity analysis was performed on 18,888 middle-aged and older people without multiple interpolations, and the results are given in We found that the risk of death decreased significantly, as the number of seconds of balance maintenance increased. After adjusting the covariates, this relationship still existed. Higher balance ability was independently related to the decrease in death risk in middle-aged and older people. The death density of middle-aged and older people whose balance ability <10 s was higher than that of those people with a balance ability ≥10 s. Consistent with a cohort study of 1,085 elderly people in Japan, standing balance predicts all-cause mortality and was independently associated with all-cause mortality . The pooThe present study found that chronic disease, overweight, and obesity had no significant effect on the association between balance ability and death. A total of 152 studies found that being overweight or obese were associated with plantar sensitivity, lower sensitivity, and decreased postural stability observed in obese people . BalanceOur study supplements further the evidence of the relationship between balance ability and death in middle-aged and older people based on the Chinese population. It is a community-based prospective study with good national representation. Stratification of factors, such as chronic disease, overweight, and obesity, was considered at the design stage, and potential confounding factors were adjusted to reinforce the existing evidence. However, the limitations of this study are that, first of all, the grouping of balance ability is uneven and does not consider the balance ability beyond 10 s may be achieved. Second, balance ability is a single body index, which needs to be combined with different measurements of body function or can improve the predictive ability of death risk. Third, all-cause deaths include deaths caused by external forces not directly related to health, such as car accidents, and there may be underreporting. Finally, overweight and death were combined in the subgroup analysis, which weakened the effect of balance ability on death in a single BMI status.In summary, the balance ability of middle-aged and older people was associated with the risk of all-cause death, and this association did not decrease with the presence or absence of chronic diseases, overweight, and obesity. The measurement of balance ability can be included as a routine examination method. When the physical examination shows that the balance ability of middle-aged and older people is significantly weakened, the reasons that may cause the balance ability to decline should be screened. For middle-aged and older people with poor balance ability and obvious clinical symptoms, it may be appropriate to increase the balance ability training to intervene and avert a fall.https://charls.pku.edu.cn/en/.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by Peking University (IRB 00001052-11014). 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.KHX planned the study, supervised the data analysis, and wrote the paper. XH performed all statistical analyses and contributed to revising the paper. XHH helped find the source and analysis method. All authors have read and approved the manuscript and they have no conflicts of interest.


In order to address the distribution of and access to cacao, 54 sherds from Late Classic Period Maya residential and civic contexts around El Pilar  were tested for the presence of cacao. Positive identification of cacao requires that the technique of laser mass spectrometry detect a significant amount of the key biomarker of theophylline to signify cacao. Results show that cacao was culturally significant and widespread and found in civic and residential units regardless of size and location. Theobroma cacao, provide the basis for a ceremonially important Mesoamerican food. Past efforts to identify cacao in ceramics focused on highly decorative vessel forms associated with elite ceremonial contexts, creating assumptions as to how cacao was distributed and who could access it. This study examines 54 archaeological ceramic sherds from El Pilar  of Late Classic (600 to 900 CE) residential and civic contexts representing a cross-section of ancient Maya inhabitants. Identification of cacao in ancient sherds has depended on the general presence of theobromine; we used the discrete presence of theophylline, a unique key biomarker for cacao in the region. Analysis was done by grinding off all outside surfaces to reduce contamination, pulverizing the inner clay matrix, extracting absorbed molecules, and concentrating the extractions. In order to obtain especially high selectivity and low limits of detection, our study utilized the technique of resonance-enhanced multiphoton ionization coupled with laser-desorption jet-cooling mass spectrometry. This technique isolates molecules in the cold gas phase where they can be selectively ionized through a resonant two-photon process. Of the sherds analyzed, 30 samples (56%) were found to contain significant amounts of theophylline and thus test positive for cacao. Importantly, cacao is present in all contexts, common to all Maya residents near and far from centers.Cacao seeds,  Cacao, known as the money that grew on trees, was brought to the world stage by Mesoamericans and the Maya  1, 2). , 2. 1, 23In recent decades, studies of cacao residues from ancient ceramics have employed methylxanthine biomarkers—caffeine, theobromine, and theophylline—ushering in a new means of addressing the use of cacao in prehistory. Chemical residue analyses have focused on vessels from elite Maya burials and caches, suggesting cacao represented wealth and power –12. CacaCacao residues from Maya samples have been associated with special and specific archaeological settings at civic centers , 15. As The examination of Late Classic Maya vessels from households around the general El Pilar area of the central Maya lowlands  and 2 prSI Appendix, Fig. S1) caffeine (C), theobromine (TB), and theophylline (TP) have been found worldwide in 100 species, including 13 orders of the plant kingdom. Most of these plants have only trace amounts of these compounds. TB and C are relatively common, while TP is rare. The few plants that do have concentrations of all three biomarkers have greater amounts of both TB and C compared with TP , TP is identified today in seven plants: Camellia sinensis, Coffea arabica, Ilex paraguariensis, Paullinia cupana, Theobroma angustifolium, Theobroma bicolor, and Theobroma cacao. This finding is corroborated by archaeological literature  to understand the implications of the identification of TP, keeping in mind that, as with many plants, their native distribution now is wider than before the great Columbian exchange 500 y ago. Our database search makes it clear that T. cacao is unique in Mesoamerica for TP, giving us confidence that any TP detected in our samples will be from cacao rather than other natural sources.The methylxanthines . We present a technique that is especially sensitive for TP, elevating the detection of TP to a key biomarker for cacao in Mesoamerica.SI Appendix, Fig. S2). For each compound, we measured standard samples of 39 pg, 78 pg, 780 pg, 1.95 ng, and 2.9 ng. Each biomarker has a different response due to different two-photon ionization efficiencies. From the slopes of these curves, we derived the relative sensitivity for TB, C, and TP as 1:2.7:4.4. The LOD is based on a signal-to-noise (S/N) level of 3 SDs in the background signal, corresponding to a signal of 1.5. Using the calibration curves, this signal translates to an LOD of 228 pg for TB, 85 pg for C, and 52 pg for TP.We established calibration curves for the analytes C, TB, and TP . Together, the 54 samples provide a window for viewing the importance of cacao among the ancient Maya .Our investigation of belongings associated with residential units and civic centers in the El Pilar area is unique in addressing the wider context of cacao consumption among the Late Classic Maya. Sample vessels were analyzed in the two phases. Our initial test of 13 vases was designed to determine if cacao could be detected . With ouSI Appendix, Table S2), we gave preference to vases (n = 40), the iconic drinking vessels, and also included storage jars (n = 6), mixing bowls (n = 4), and serving plates (n = 4). Sampling procedures incorporated the nature of the sites from which these belongings were collected, representing 10 residential units and 4 civic centers , and examples of each form evince the presence of cacao biomarkers.The historical record of cacao consumption begins with Spanish accounts. Vases, sometimes referred to as cups , have be64 centers . Our comSI Appendix, Table S2). Indeed, there are images on vases (mole de cacao?While vases dominated the study (74%), samples of all domestic ceramic forms allow us to investigate the consumption of cacao by the Late Classic Maya. Interestingly, positive designation for cacao was determined for all forms, not just the designated drinking vessels. Chemical traces of cacao were present in bowls for mixing, jars for storage, and plates for serving . If cacao was employed in prestigious rituals, such events were shared by all ranks of society.This study emphasized residential settings, yet included examples from civic-ceremonial places as well, demonstrating a significantly wider role of cacao consumption than has been assumed. We conclude that cacao biomarkers are common in many Late Classic contexts, and can be recognized in all basic domestic vessel forms, across every landform in the El Pilar area, in residential units of every status and, of course, in civic centers  laser desorption (LD), 2) jet cooling (JC), 3) resonance enhanced multiphoton ionization (REMPI), and 4) MS.L2MS is a four-stage process, schematically depicted in The sample is mixed with graphite and mounted on top of a translating substrate from which the analyte is desorbed by a focused Nd:YAG laser pulse . LD vaporizes the molecules intact, permitting detection at the parent mass peak. This LD technique has been used to successfully desorb a large variety of neutral molecules intact ranging from hydrocarbons to polymers with masses up to 8,000 Da –84.Desorption occurs directly in front of a pulsed valve , which produces a molecular beam of argon that entrains the desorbed molecules and cools them to ∼20 °K. This low temperature permits very high-resolution spectroscopy in combination with fragment-free MS.SI Appendix, Fig. S4 shows REMPI spectra for the three methylxanthines in this study.The ionization process is of the cold gas molecules through a two-part, two-photon process. The first tunable photon resonantly excites the molecule in a vibronic transition and the second photon ionizes the excited molecule. At the low temperatures in this technique (circa 20 °K), the optical spectra are highly and uniquely resolved for each molecule. As a result, it is possible to selectively ionize and detect a specific molecule from a complex sample. Both photons are produced by an EKSPLA PL2251 Nd:YAG laser system (30-ps pulse duration). The excitation photon is produced by an optical parametric generator which converts 355-nm light into tunable UV pulses (80 to 120 uJ per pulse). The 1,064-nm and 532-nm pulses from the Nd:YAG are combined to harmonically generate 213-nm light (0.2 mJ). This 213-nm light is used for the ionization completing this step.The final step is the detection of the ions by a time-of-flight mass spectrometer , 79, 85.We can quantify the ratio of the three biomarkers by using two different resonant wavelengths to simultaneously excite C and TB or C and TP, each at their own resonant wavelength . Two lasers are used concurrently, one exciting C and the other exciting either TB or TP. At the same time, a third laser at 213 nm ionizes all excited molecules.The ions of each ratio pair are separated in the mass spectrum and their mass peaks are compared to obtain the ratios. TB and TP have the same mass so their ratios are obtained indirectly by comparing the other two ratios. The main source of signal variations in L2MS is the LD step, so measuring two compounds simultaneously in the same LD sequence greatly improves the S/N in the measurement of their ratios.Each replicate on the bar was measured twice, once for the C/TB pair and once for the C/TP pair. In each measurement, the two wavelengths stay constant while the sample is moved. Each measurement of a sample involves 12 iterations of measurement, each iteration averaging 40 laser shots.Signal represents integrated mass peaks with the background subtracted. Background is determined in two ways: 1) in an area of the mass spectrum where no mass is detected and 2) by measurements with the desorption laser blocked.Supplementary File


Aging is accompanied by many chronic comorbidities and disabilities, and entails medical expenses, which affects the quality of life among older adults. The purpose of this study was to investigate whether the health status of older adults with chronic diseases mediates chronic disease self-management to predict quality of life. Methods: This research adopted a cross-sectional correlation study design. Convenient sampling was performed in outpatient departments commonly visited by older adults in a medical center in Southern Taiwan. The following measures were collected: (1) Physiological measurement: left handgrip, right handgrip, and lower extremities’ muscle strength. (2) Questionnaires: cognitive function was measured by the Alzheimer’s disease (AD)-8 scale, possible frailty with the Kihon Checklist (KCL), functional status with the Barthel Index (BI) and the Lawton and Brody Instrumental Activities of Daily Living (IADL) scales, and self-management for chronic disease and quality of life with the (WHOQOL)-BREF, Taiwan version. Results: Chronic disease self-management is correlated with health status and is directly related to quality of life. Chronic disease self-management also indirectly affects quality of life through health status (cognitive status and risk of frailty), showing that health status partly mediates the correlation between chronic disease self-management and quality of life. Conclusions: A health status feedback system should be introduced in related chronic disease self-management measures for older adults so that they can be aware of their own health status and so that their quality of life is improved. Custom-made nursing interventions are necessary for the reduction in or delay of disability or risk of frailty in older adults, thereby enhancing their quality of life. Aging leads to decreased physical activity, mood disorders, social isolation, and increased risk of chronic diseases. With increases in age, frailty accompanied by cognitive disorders may occur in older adults, and the deterioration of organ functions may increase the negative effects on the body, causing reductions in independent living skills  and lossProlonging life is a very important public health goal that emphasizes quality of life and independent living . Many coSelf-management is crucial for improving the health and quality of life for older adults with chronic diseases . LookingMany studies have pointed out that self-management may have impacts on physical functions, cognitive functions, and quality of life. For example, a cross-sectional study explored the correlation among the self-management ability, frailty, and perceived poor health among older adults in the community. The results showed a significant correlation among self-management ability, frailty, and perceived poor health. Self-management ability was negatively correlated with perceived poor health, while frailty was positively correlated with perceived poor health . One earPrevious literature shows that higher self-management is correlated to a better health status and higher quality of life, and that a higher health status is associated with a better quality of life. However, studies on how older adults achieve a satisfactory quality of life or wellbeing, and whether it is achieved through other mediators, are not common. Thus, the purpose of this study was to examine the relationship between self-management and quality of life, and investigate the mediating effect of health status among older adults with chronic illness in Taiwan. Understanding the mediation of health status to self-management and quality of life would benefit the development of new interventions in the future.A cross-sectional correlation study design was used.2 (0.13) of Cohen’s (1988) gold standard to estimate multiple correlations. The required sample size was calculated to be 98 participants. Because we anticipated receiving invalid questionnaires, an additional 10% of the sample (10 participants) was added, for an estimated sample size of 108 participants.Convenience sampling was adopted, and participants were recruited from among the older adults in the neurology, cardiology, metabolism, rehabilitation, and family medicine outpatient departments in hospitals in Southern Taiwan (26). Subjects were eligible for the study if they met the following criteria: (1) older adults with a confirmed diagnosis of chronic diseases, (2) those aged 60 years and older, (3) those with no diagnosed dementia, disability, hearing problems, or communication disabilities, (4) those who were able to communicate in Chinese or Taiwanese, and (5) those who agreed to participate in the study. The sample size was estimated using SAMPLE POWER version 2.0 software , in which the statistical power and signiﬁcance were set at 0.80 and 0.05, respectively. The study adopted the medium level of RStudy samples were selected by the research team through their prearranged physician appointments. The RAs reviewed clients’ charts first, and then held discussions with physicians concerning candidate participants who met the inclusion criteria. Then, cases were invited by an RA to participate while waiting for their appointment. Subjects were interviewed in person, and the data were collected in outpatient departments. Surveys and physiological measurements were conducted by trained research assistants. The research assistants were given instructions and interviewer training for consistency before the implementation of this research project to ensure the accuracy of the data.Baseline attributes included sex, age, marital status, living conditions, religious beliefs, level of education, work, and economic conditions. Disease characteristics included disease diagnoses, number of diseases, and Charlson comorbidity index (CCI) scores. The CCI was developed by Charlson and colleagues in 1987 as a comorbid severity adjustment tool to control for comorbid diseases before treatment or surgery and to track patient prognosis. It has been well-validated, and can be used to calculate the total score for 19 disease conditions for predicting one-year mortality: the scores range from 0 (no condition) to 6. A higher score indicates a more severe comorbidity burden .Functional status. In this study, the Barthel Index (BI) and the Lawton and Brody Instrumental Activities of Daily Living (IADL) scales are utilized. The BI scale measures performance in ten activities of daily living (ADLs). Each respondent’s response is divided into the “with help” and “independent” categories. The total score ranges from 0 to 100, where a higher score indicates higher functional performance in ADLs . The BI Physiological measurement. In this study, vision, hand grip, and lower extremity muscle strength were measured. The chair stand test was used as a measure of muscle strength. The participants were asked to stand up from a chair from a sitting position and then to sit down again, and the number of whole sets completed within 30 s was calculated  to measuPossible frailty. The Kihon Checklist (KCL), developed by the Japanese Ministry of Health, Labor, and Welfare, was used to identify older adults at risk of requiring care/support. The KCL comprises 25 items (yes/no) divided into seven domains: activities of daily living (items 1–5), physical strength (items 6–10), nutrition (items 11–12), oral function (items 13–15), socialization (items 16–17), memory (items 18–20), and mood (items 21–25), and has been used for screening frailty among older adults . The sumCognitive function. Cognitive status was assessed using the Alzheimer’s disease (AD)-8 scale. This scale is mainly used to detect early symptoms of dementia in adults . A totalThe chronic disease self-management scale was developed based on the related literature ,32. It cIn this study, the World Health Organization’s (WHO) Quality of Life (WHOQOL)-BREF, Taiwan version, , was useAfter this study was approved by the institutional review board , the study subjects were given a study consent form, after which the researcher monitored the subjects’ progress during the study period. The researcher explained the purpose of the research and process to each research subject, who were allowed to withdraw at any time. The interviewees’ rights and interests were assured. The data were applied only in this study, and were not made public.Data were analyzed using SPSS-V22 software. Descriptive statistics were used to summarize demographic data. The relationships between variables were tested using the Pearson correlation coefficient (г). For further analysis, a path analysis was applied to explore the mediating effects of the health status on the antecedent (chronic disease self-management) and the outcome  variables. In this study, α = 0.05 was set as the criterion for significance in the statistical analysis.A total of 115 participants were included in this study, of which three were excluded because of incomplete data. The majority of the participants were women (62.3%), with an average age of 72.6 ± 7.49 (range of 60 to 99) years. Most of the participants were married (78.9%), and 91 participants (83.3%) lived with their families. In terms of religious beliefs, 45.9% were Buddhists, and most participants (53.7%) had a high school education or higher. More than 90% of the participants did not have a full-time job. The average total number of diseases among the participants was 1.6, with 58.9% having at least one disease and 27.7% having two diseases. The most prevalent chronic disease was hypertension, followed by cardiovascular disease, diabetes, hyperlipidemia, arthritis, fractures, and cataracts. In terms of the severity of disease, 50 participants (44.6%) scored “0”, followed by 24 (21.4%) scoring four, as demonstrated using an age-adjusted CCI .The average score for ADLs was 98.7 ± 6.1 (range of 50 to 100), and that for IADLs was 22.0 ± 3.4 (range of 4 to 24). Only 42.9% of participants did not present early symptoms of dementia, as measured using the AD-8. The results revealed that 10 (8.9%) participants exhibited a risk of frailty in the lifestyle domain, whereas 24 (21.4%), 1 (0.9%), 26 (23.2%), 16 (14.3%), 58 (51.8%), and 30 (26.8%) of the participants had poor physical strength, a poor nutritional status, low oral functions, were house-bound and isolated, had low cognitive functions, and a risk of depression, respectively . Howeverp = 0.001–0.05). In addition, left and right handgrip strengths, cognitive function, risk of frailty, IADLs, and ADLs and quality of life were significantly correlated   .p = 0.008, a2 = 0.178, p = 0.003, a3 = −0.045, p = 0.007, a4 = 0.075, p = 0.000, and a6 = −0.0933, p = 0.000), with the exception of ADLs . Among the health status items, only cognitive function  and risk of frailty  had a significant impact on quality of life. Pathway a and pathway b indicated that efficient chronic disease self-management could generate a favorable health status (except for ADLs), and that a lower risk of impaired cognition function and frailty could lead to a high quality of life. The bootstrap method used by Preacher and Hayes [p ≤ 001), the correlation between chronic disease self-management and quality of life achieved significance  after the health status was controlled for. Thus, the mediating effects of cognitive function and risk of frailty accounted for 21.5% and 26.0%, respectively, of the total effect  (2 = 0.449) of the variance in quality of life  and the outcome variable . After controlling for personal attributes and disease characteristics, the path analysis showed that chronic disease self-management had a significant impact on items related to the health status of the subjects  . The per of life .To the best of our knowledge, this is the first study on the correlation among older adults’ level of self-management, health maintenance, and quality of life. It provides new insights by considering the complex relationships among self-management, health maintenance, and quality of life. The study results showed that chronic disease self-management can both directly and indirectly affect the quality of life of older adults with chronic diseases, and that cognitive function and risk of frailty can partly mediate the correlation between self-management and quality of life, indicating that those with efficient self-management have fewer cognitive risks and frailty problems in addition to a higher quality of life. Recent studies have indicated that cognitive impairment has a direct impact on self-management ,18, suchThe results of the present study indicate that the adequacy of one’s living allowance is correlated with quality of life, indicating that those with adequate living allowances had a higher quality of life than those with inadequate living allowances, which is consistent with the findings of other researchers . RetiremTo prevent the consequences of chronic diseases as well as the limitations and obstacles caused by old age, and to improve quality of life, multiple interventions are required. Before and after performing a self-management intervention in older adults whose frailty and cognitive functions may be affected by such interventions, the important thing is to include the screening of their frailty status in addition to their physical and cognitive functions related to routine self-care, as well as to follow-up changes in frailty status and physical and cognitive functions . Due to Interpretation of the results of this study is limited by several factors. First, the cross-sectional nature of the study limits generalization. The sample of this cross-sectional study came from outpatients, and could be biased. It could be an overestimation of the patients’ self-management. We would suggest that a future study could be initiated to investigate a sample apart from outpatient clients. In addition, health status and chronic disease self-management are affected by multiple factors. Therefore, future research involving longitudinal studies are needed. Second, only 15 (13.4%) of the participants were considered to have multimorbidity. These data are relatively low compared to that of Taiwan. The low proportion could be due to small samples. Future studies should include more subjects so as to reduce biases. Third, the participants in this study were not limited to a specific chronic disease, and therefore the range of diseases was wide. Subjects with different diseases may have different self-management strategies, health statuses , and qualities of life, which is also a limitation of this study. Finally, this study used the AD-8scale to subjectively measure the cognitive status of the participants instead of using a neuropsychological test battery to capture the specific category of cognitive impairment. In the future, the participants’ cognitive status should be objectively measured, and subjects in need of help in various dimensions of quality of life, such as physiology, psychology, society, and environment, should be identified.To the best of our knowledge, this study is the first to clarify that health status plays a mediating role in the correlation between chronic disease self-management and quality of life among older adults with chronic diseases. Chronic disease self-management was negatively correlated with very early dementia and risk of frailty, which were the health status variables. Negative correlations were noted between health status  and quality of life. A positive correlation was noted between chronic disease self-management and quality of life. The next steps will be to evaluate these factors in interventions to confirm the findings of these results.