Doubt is subjective uncertainty about one’s perceptions and recall. It can impair decision-making and is a prominent feature of obsessive-compulsive disorder (OCD). We propose that evaluation of doubt during decision-making provides a useful endophenotype with which to study the underlying pathophysiology of OCD and potentially other psychopathologies. For the current study, we developed a new instrument, the Doubt Questionnaire, to clinically assess doubt. The random dot motion task was used to measure reaction time and subjective certainty, at varying levels of perceptual difficulty, in individuals who scored high and low on doubt, and in individuals with and without OCD. We found that doubt scores were significantly higher in OCD cases than controls. Drift diffusion modeling revealed that high doubt scores predicted slower evidence accumulation than did low doubt scores; and OCD diagnosis lower than controls. At higher levels of dot coherence, OCD participants exhibited significantly slower drift rates than did controls . In addition, at higher levels of coherence, high doubt subjects exhibited even slower drift rates and reaction times than low doubt subjects (q<0.01 for 70% coherence). Moreover, under high coherence conditions, individuals with high doubt scores reported lower certainty in their decisions than did those with low doubt scores. We conclude that the Doubt Questionnaire is a useful instrument for measuring doubt. Compared to those with low doubt, those with high doubt accumulate evidence more slowly and report lower certainty when making decisions under conditions of low uncertainty. High doubt may affect the decision-making process in individuals with OCD. The dimensional doubt measure is a useful endophenotype for OCD research and could enable computationally rigorous and neurally valid understanding of decision-making and its pathological expression in OCD and other disorders. Making decisions promptly and accurately is fundamental to adaptive functioning. Individual differences in this ability may reflect differences in underlying physiological processes and related cognitive traits, and in extreme cases may give rise to specific psychopathology. A rigorous scientific understanding of this dimension and its pathological expression requires the characterization of the mechanisms of decision-making, their sources of variability, and their points of vulnerability.An important component of the decision-making process is having confidence in the information necessary to make a decision. Doubt has been described as a lack of subjective certainty about, and confidence in, one’s perceptions and internal states . Doubt iHowever, we know of no evidence that a dimensional cognitive trait underlies the decision-making process in unaffected individuals, or that a disrupted decision-making process in OCD is related to a dimensional trait of doubt. Furthermore, we know of no evidence linking variation in this dimensional trait, or evidence linking it or OCD to a dimension of neurophysiological variability. A reliable and valid dimensional measure of doubt would provide a means of investigating these hypotheses.A plausible model of doubt is that it represents the rate of internal computations that determine decisions and the neurophysiological basis for these computations. A valid neurophysiological and computational model of decision-making would therefore define cognitive traits as the consequence of variability in the processes by which individuals integrate information and direct their behavior. More specifically, individual variability can be explained by neurophysiological parameter differences in the computations underlying decision-making. Here, we aim to measure doubt and determine whether variation in this trait reflects variability in underlying neurophysiological processes that reflect computational parameters of decision-making.The studies presented in this paper describe the development of a measure of doubt and address the hypotheses that a) individuals vary along a cognitive dimension, doubt; b) this dimension is relatable to the computational parameters that describe how external evidence is accumulated for decision-making under uncertainty; and c) extremes on this dimension are observed in patients with OCD. To test these hypotheses, we developed a multi-item questionnaire that measures doubt, examined its dimensionality, and evaluated its psychometric properties in individuals who completed an internet survey. We also compared doubt scores in individuals with OCD and in community volunteers. We then evaluated performance on a decision-making task in individuals with and without OCD, as well as those scoring high or low on doubt, using a random dot motion paradigm to assess computational parameters based on the “drift diffusion” model of decision-making .This study was approved by the Johns Hopkins Medical Institutions Institutional Review Board IRB2 . Written consent was obtained.The initial item pool for the DQ was generated by clinicians (Drs. Nestadt and Krasnow) expert in the evaluation and diagnosis of OCD and anxiety disorders in patients and in participants in family and genetic studies of OCD. The items were devised to capture the experience of doubt in several domains, including memory, decisions, task accuracy and completion, visual perception, and auditory perception. After input from other clinicians and researchers, a preliminary version of the instrument was developed, containing 21 items, including two items from the “Doubts about actions” subscale of the Multidimensional Perfectionism Scale . In the first phase, there were two separate postings of the questionnaire. First, a link was made available on a public Facebook page (https://www.facebook.com). Participation was anonymous, and no feedback was provided to the N = 67 participants. Second, the electronic questionnaire was posted online on the OCD Research webpage, within the protected Johns Hopkins University server. Participation was anonymous, but the N = 85 participants were given feedback on their scores, based on the mean and standard deviation of the scores on the first posting. Combining the two samples, there were 152 participants in this first phase.An internet form of the DQ was created on the Qualtrics survey platform  : “After The 152 individuals in this first phase ranged in age from 17–83 years ; 46 males, 95 were females, and 11 did not provide their gender. The Student t-test was used to compare doubt scores in men and women, and analysis of variance was used to compare total DQ score across YBOCS doubt ratings. Factor analysis on the 18-item DQ was performed using varimax rotation, and the scree plot was used to estimate the number of factors. We also conducted parallel analysis as an alternative, statistical approach for determining the number of components, using an SPSS program developed for this purpose .In the second (test-reliability) phase, students or staff who responded to a request for study participants on the Johns Hopkins University web-based “bulletin board” completed the DQ at two time points, at least one month apart . There were 158 participants in this phase ; their ages ranged from 17–59 years . The intraclass correlation coefficient was used to evaluate the test-retest reliability for the total doubt score.A total of 67 OCD patients, diagnosed according to DSM-IV criteria , were reSeventy individuals (26 OCD participants and 44 controls) were recruited from the JHU OCD and Anxiety Disorders Clinics, from an ongoing genetic study of OCD, and from respondents to postings on JHMI and JHU student and staff web sites, for the behavioral task. Forty-six of these participants also completed the DQ (12 OCD participants and 34 controls).To evaluate decision-making in these individuals, the random-dot motion task (RDMT) was used , 19, as The task consisted of a practice session and performance under three separate conditions. The first condition included seven coherence levels with monetary feedback. The second condition included six coherence levels and assessed subjective certainty following the decision. However, our results suggest that high were directed to record their level of certainty based on the decision they made on the dot motion. They completed this on a computerized scale ranging from 1 (low certainty) to 7 (high certainty). The third condition, with six coherence levels, introduced a monetary penalty for slow responses, as well as a monetary incentive for fast responses, individualized for reaction time to measure the speed-accuracy trade-off. A response time (RT) greater than 1 standard deviation above the individual’ average RT, calculated from the first condition, was penalized $2.00. Participants received increasing monetary feedback for faster responses and were told that they would receive a proportion of their rewards after completion of the experiment. The primary outcome measures were accuracy, RT, and subjective certainty ratings.As in Banca et al. , hierarc139 = 0.40, p = 0.69). The DQ score was moderately negatively correlated with age .In the first internet phase, completed by 152 participants, scores on the DQ ranged from 18 to 83  . The valThe doubt scale had high overall inter-item reliability, with the Spearman-Brown Coefficient = 0.89, and Cronbach’s α = 0.91; this value did not appreciably change, ranging from 0.90–0.91, after individually deleting each item.Five components, with eigenvalues >1.0, were extracted in the factor analysis of the items. The first component, with eigenvalue = 7.53, explained 41.8% of the variance; the next four components explained 7.9%, 7.2%, 6.0%, and 5.7% of the variance, respectively; the cumulative variance explained was 68.7%. The scree plot suggested a single factor structure for the items in the DQ .DQ scores were correlated with the YBOCS doubt rating, with mean doubt scores increasing from 37.1 in those rated as having no doubt; 48.5 in those with mild doubt; 56.4 in those with medium doubt; 66.7 in those with severe doubt; and 72.3 in those with extreme doubt  and 54.0 (SD = 13.2) at first and second completions, respectively. There was an inverse relationship between age and DQ score at the first assessment . The mean difference in doubt scores between the two periods was 0.34 (SD = 7.2). The one-month test-retest reliability of the DQ was excellent .88 = 4.09, p<0.001). The distributions of doubt scores between the OCD and comparison groups were significantly different  . From the ROC analysis, the estimated area under the sensitivity vs. (1-sensitivity) curve was 0.76 (95% CI = 0.66–0.87), p<0.001 , which was not substantially different from the distribution in the internet respondents. In contrast, in OCD cases, the mean doubt score was 58.4 , significantly greater than in the internet respondents (t<0.0001) . Using aDrift rate was calculated for each of seven ‘coherence’ levels (0.5%–70%) using HDDM in 26 OCD cases and 44 control participants who completed the RDMT in the no cost (first) condition. In a high uncertainty, low coherence (5% coherence) condition, no significant differences in modeled drift-rate was observed between OCD patients and controls. However, in the higher coherence (most certain) conditions, the OCD cases manifest significantly slower reaction times, and HDDM-modelled drift rates . Both grWe sought to investigate whether doubt might be a predictor of subjects’ RDM performance. We obtained doubt scores for a subset of the OCD and control participants included in the previous data. Individuals with high scores on the DQ  showed a significantly higher reaction time and lower modeled drift rate than participants with a low DQ  score, but only in the highest coherence (most certain) condition . The dif2 = 0.11; p <0.05) and for control participants , exclusively at the 70% coherence level. We found no correlation between doubt score and threshold. The correlation between the drift rate and the doubt score was not significant for OCD cases alone, which may be attributable to the low number of OCD cases (N = 12) completing both the DQ and the RDMT, or heterogeneity among patients with OCD. However, the best-fit regression slopes between control and OCD subjects were not significantly different (p = 0.44)  .A posterior distribution of group mean decision thresholds was calculated, using HDDM, over five different coherence levels when subjects were incentivized to respond quickly (third condition). As reported above, under no cost conditions (first condition) there was no effect of coherence level on decision threshold; neither was there any effect of coherence on the threshold for OCD, control, or low doubt subjects. However, with higher coherence, high doubt subjects exhibited lower evidence thresholds than low doubt subjects (q<0.05 for 45% and 70% coherence levels).In the second condition of the RDMT, participants reported the confidence with which they made their decisions with scores ranging from 1 (low confidence) to 7 (high confidence). The pooled distributions of confidence scores, based on correct trials, showed that high doubt subjects (n = 10) report less confidence than low doubt subjects (n = 36) when evidence accumulates more quickly, i.e. with the high coherence, less ambiguous tasks. We report the chi-squared statistic, which indicates that the higher coherence  distributions are significantly distinct between the two groups, <0.005 in each test. The 12 OCD subjects for whom we collected a doubt score exhibited less confidence than the 34 controls at all but the lowest coherence level, p<0.005.Variability in the neurophysiological processes by which an individual accumulates information and directs his/her behavior may form the basis for individual differences in cognitive traits, and in some cases give rise to psychopathology. In this study, we focused on doubt, defined as a lack of subjective certainty or confidence in one’s perceptions, as a cognitive dimension linked to individual differences in computational parameters, the values of which define how external evidence for decision-making under uncertainty is accumulated.To quantify doubt, we developed the DQ, and employed it in an internet sample and in the clinic. The DQ showed excellent psychometric properties, with doubt scores in the internet sample showing an approximately normal distribution, and factor analysis suggesting that a single factor underlies the doubt construct, with excellent inter-item reliability. External validation of the DQ was evidenced by a strong association of doubt scores with a self-completed assessment of the YBOCS doubt item (an item that does not presuppose the presence of obsessions). Moreover, doubt scores were significantly higher in OCD-affected than control participants, even after adjusting for age differences. Moreover, doubt was inversely associated with age in participants in both internet surveys, suggesting that the doubt score is not influenced by age-related memory decline.We also found that doubt was associated with decision-making performance on the RDM task. Those with high doubt scores showed significantly slower reaction times and estimated drift rates than those with low doubt, under less uncertain conditions, although there was no effect on the computed decision threshold. Those with high doubt, moreover, reported less certainty in their responses. Together, these findings support both the validity of the DQ and a behavioral measure  with which to assess individual variation in decision-making and doubt.Self-report and behavioral approaches to measurement in behavioral research often lack agreement. This has been recognized, for example, in the measurement of other decision-making constructs and in ‘impulsivity’ , 22. TheThe pathological expression of doubt is considered a paramount feature of OCD. There is a long tradition of the clinical importance of doubt in OCD –27. MoreThe findings, comparing OCD participants and controls, are comparable to those comparing high and low doubt participants. OCD participants exhibit slower estimated drift rates than control participants, with no evidence of different decision thresholds. They also report lower certainty in their decisions than the controls. This provides further support for the presence of higher doubt measures in patients with OCD. A significant difference in drift rate between OCD subjects and controls in the highly coherent decision doubt and OCD are not equivalent, as the correlation between doubt scores and drift rate under low uncertainty conditions was observed even in those without OCD; moreover, the correlation between drift score and doubt score was greater for controls than for OCD participants. Participants with OCD exhibited a wide range of doubt scores, albeit typically in the higher range. Given the clinical heterogeneity of OCD, we suspect that doubt may contribute to the development of many but not all cases of OCD. Further prospective research is necessary for elucidating the contribution of doubt, and the interaction between doubt and other underlying traits, to the development of OCD.Banca et al.  employedIn this study, we found that the slower drift rate was most evident in the more coherent, less ambiguous choices, which is consistent with prior OCD studies . We haveThe subjective reports of certainty reflect the presence of doubt in both the high doubt and OCD groups, particularly in the least ambiguous tests, and most strongly in the OCD comparisons. This was not observed in the findings reported by Banca et al. [9), but has been shown in other OCD studies , 32. IntWhat neurophysiological explanation could there be for limitations on the rates of evidence accumulation that we and others have observed? In the RDM task, the overall direction of the moving dots is uncertain. This assessment might be computationally conceptualized as an assignment of a probability (or belief) to each possible external state of the world. As new evidence occurs, these probabilities are updated in a Bayesian manner. When the probability profile, or belief state, reaches a relevant threshold, a behavior might be released or suppressed. In the RDMT, and in many choices in daily life, one’s belief state must be sufficiently near absolute certainty to release a behavior. Correspondingly, all other belief states must be sufficiently near 0. In more certain circumstances, evidence for one state accumulates quickly. In this situation, an efficient updating process would quickly suppress alternative beliefs to 0 while elevating the belief for the most-likely state towards 1. In a drift-diffusion model, the drift rate reflects this update rate. We find that high-doubt individuals exhibit slower drift rates at the highest levels of coherence in the RDM task, suggesting an inability to rapidly update belief towards more extreme values (0 or 1). When coherence is low, and uncertainty is high, evidence occurs slowly, and an update process with limited speed is not taxed. Reaction time also reflects the belief threshold required to release a behavior, which is reflected in the threshold measured by the drift diffusion model. An ideal threshold optimizes a speed-accuracy tradeoff.The importance of the findings in this study is the correspondence between self-report questionnaire, behavioral measurement and a clinical syndrome OCD; each of these domains of assessment provide critical information relevant to understanding a condition. These different perspectives, together with several others, from the molecular to the neurophysiological, provide their own focus and contribution to the understanding of the condition.Several potential limitations of the current study must be acknowledged. The internet sample of respondents may not be representative of the community, and the distribution of doubt scores in a more representative community sample must be examined. Moreover, the OCD case and control groups may not be representative of OCD cases and non-cases, respectively. Indeed, since the non-clinical comparison individuals were not evaluated for OCD, it is possible that some of them met criteria for a diagnosis of OCD, which would lead to under-estimation of the difference in doubt scores between OCD and non-OCD individuals. Although age and gender did not explain the higher doubt score in the OCD cases than control group, there may be other unmeasured demographic or clinical factors that might confound the relationship. It is important to acknowledge that HDDM is a hypothetical approach for understanding the process of decision-making, and alternative approaches may prove more appropriate. In future research, it would be useful to evaluate the encoding of sensory input, as distinct from the drift rate, and to determine whether doubt influences this process , 34.Future studies are needed to evaluate the DQ in a larger number of individuals, and in more representative, community and clinical samples, so that useful norms can be derived for clinical and research applications. Moreover, research is needed to determine how doubt scores are influenced by demographic characteristics, clinical features , and life experiences. Of particular interest for OCD research is to determine if the severity of doubt is predictive of the development and severity of obsessions and compulsions, and to further explore whether therapeutic reduction of doubt can alter the course and severity of the disorder –31.Further work also is needed to investigate the relationship of doubt to other psychiatric disorders, and the characteristics of apparently healthy persons who exhibit doubt. Determining the cognitive-behavioral and neurobiological underpinnings of the doubt dimension as an endophenotype for specific psychopathology should move the field further by taking advantage of the burgeoning understanding of perceptual decision-making and the neurocircuitry of decision-making, and may help to direct the development of more effective, rational treatments for OCD and other disorders.S1 Fig(PDF)Click here for additional data file.S2 Fig(PDF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.


Benzoyl and stearoyl acid grafted cellulose were synthesized by a simple chemical grafting method. Using these as chemical adsorbents, polycyclic aromatic hydrocarbons (PAHs), like pyrene and phenanthrene, were effectively removed from aqueous solution. The structural and morphological properties of the synthesized adsorbents were determined through X-ray diffraction analysis (XRD), thermal gravimetric analysis (TGA), Fourier transform infrared (FT-IR), FE-SEM, and NMR analyses. Through this method, it was confirmed that benzoyl and stearoyl acid were successfully grafted onto the surface of cellulose. The 5 mg of stearoyl grafted cellulose (St–Cell) remove 96.94% pyrene and 97.61% phenanthrene as compared to unmodified cellulose, which adsorbed 1.46% pyrene and 2.99% phenanthrene from 0.08 ppm pyrene and 0.8 ppm phenanthrene aqueous solution, suggesting that those results show a very efficient adsorption performance as compared to the unmodified cellulose. Industrial and agricultural contaminants, the number of which has dramatically increased due to worldwide development, are the most serious pollutants globally. Water resources can be contaminated with organic compounds, which are highly hazardous in every aspect. It has been reported that organic molecules in water from manufacturing activities, such as dyes, agrichemicals, and combustion byproducts, are not only a global concern owing to their long-term potential risk to ecosystems, but also have an effect on human health due to their high toxicity and low biodegradability . Therefo2 and H2O, by chemical treatments . I. I− ion  125 ppm b. In theum range a. The 1Hr 35 ppm b.−1, which corresponds to hydroxyl group valence vibrations in cellulose, was observed in the pure cellulose. In the case of the Bz–Cell and St–Cell, this band was not observed because of the esterification reaction of pure cellulose, which modified with benzoyl and stearoyl chloride on an OH-group of the pure cellulose (−1) was also observed due to the esterification of the Bz–Cell and St–Cell  of pure cellulose, and the benzoyl and stearoyl cellulose materials, against weight loss (%), are plotted in ectively . These rThe influence of the crystalline behavior of pure cellulose and the modified celluloses of the esterification reaction on the crystallinity of cellulose were studied by wide angle XRD. FE-SEM was used to study the morphological characteristics of the inclusion complex. The SEM images of cellulose, Bz–Cell, and St–Cell are shown in To clarify the sorption effects of PAHs onto the Bz–Cell and St–Cell, the fluorescence emission spectra of the PAHs were measured in the phenanthrene and pyrene solution of 0.8 and 0.08 ppm. After 24 h of stirring to equilibrate between the adsorbents and PAHs in aqueous solution, the emission spectra of the remained PAHs in solution were measured for the analysis. Each experiment was triplicated to obtain mean results  . The intFinally, the regeneration and reusability of the Bz–Cell and St–Cell for the sorption of the model PAHs were examined. Cellulose materials, modified by benzoyl and stearoyl groups, were prepared by a simple chemical grafting method. Using these reactions, functionalized cellulose, the Bz–Cell and St–Cell respectively, was successfully synthesized. The characterization results that were obtained by NMR, FT-IR, TGA, XRD, and SEM indicated that the benzoyl and stearoyl groups were grafted on the cellulose backbone. The Bz–Cell and St–Cell were estimated to have ability of potential adsorbents to remove two model of PAHs (phenanthrene and pyrene) in adsorption study. Especially, both the removal and reusability efficiency of St–Cell are higher than those of Bz–Cell, as shown in


Background: Evidence has shown that the greater the accumulation of risk factors for stroke, the greater the risk of stroke. Early intervention in the accumulation of risk factors for stroke can effectively reduce the incidence of stroke. The study aimed to investigate the distribution of the number of certain risk factors for stroke  and to explore the cause of the accumulation of certain stroke risk factors.Methods: A total of 4,052 participants aged 40 years or older were selected by the multistage stratified cluster sampling method in Dehui City in Jilin province, China. Descriptive data analyses were conducted. Multiple regression analyses were used to explore the adjusted association between the accumulation of key stroke risk factors and subjects' lifestyle and demographic characteristics.Results: Overall, 84.1% of the participants in this study had one or more of the four certain risk factors for stroke. The odds ratios (ORs) and 95% confidence intervals (CIs) of having ≥1, ≥2, and ≥3 key stroke risk factors were 1.627 , 1.446 , and 1.394 , respectively, for males compared to females. Similarly, the ORs and 95% CIs of having ≥1, ≥2, and ≥3 key stroke risk factors were 1.227 , 1.256 , and 1.450 , respectively, for partially salty diets compared to normal diets. Compared to people who did not exercise regularly, the ORs and 95% CIs of having ≥1, ≥2, and ≥3 key stroke risk factors were 0.693 , 0.800 , and 0.775 , respectively, for people who regularly exercised. Compared to people who without a family history of cerebrovascular diseases, the ORs and 95% CIs were 1.418 , 1.327 , and 1.209 , for people who with it.Conclusions: Male, partially salty diets, and family history of cerebrovascular diseases were risk factors for the accumulation of certain stroke risk factors while regular physical exercise was a protective factor. Stroke is typically characterized as a neurological deficit attributed to an acute focal injury of the central nervous system by a vascular cause , and is Blood pressure, blood lipids, blood glucose, and BMI are indicators that can be objectively measured in cross-sectional studies. Therefore, recall bias and other possible information bias can be effectively avoided. Hypertension, overweight or obesity, diabetes, and hyperlipidemia are well-established major risk factors for stroke with high population attributable risk . At the This population-based cross-sectional study was part of the Stroke Screening and Prevention Programme of the National Health and Family Planning Commission of China. The survey was conducted in 2016 and supervised by the National Center for Stroke Control and Prevention. In this study, we explored the distribution of the number of risk factors for stroke. Adjusted associations between the number of accumulated stroke risk factors and demographic characteristics and lifestyle were also examined in order to clarify the strength of association.This population-based cross-sectional study was conducted among residents aged 40 years or older and were living in Dehui City for over 6 months in 2016. The multistage stratified cluster sampling method was used to select the study sample in Dehui City in Jilin province, China. In the first stage, the districts of Dehui city were divided into rural and urban area. In the second stage, 30 villages  and 10 towns (urban) were randomly selected using probability proportional to size (PPS) sampling. In the third stage, 4 or 5 communities were sampled from both urban and rural area using PPS. Finally, 1 adult resident was randomly selected from each household of the selected communities , and written informed consent was obtained from all the participants.All data were collected by an interviewer administered questionnaire. The questionnaire was composed of three parts: general information , body measurements , and laboratory results (such as blood lipids). The investigators had been uniformly trained and followed the same questionnaire instruction. Eligible investigators had to pass an examination at the end of training.The subjects' heights and weights were measured without shoes and wearing light clothing according to a standardized protocol and technique. The accuracy of the measurement were 0.1 cm and 0.1 kg, respectively. Blood pressure was measured using an electronic sphygmomanometer (OMRON HEM-7200). Each participant rested for at least 20 min before measurements were taken, and the average value of two measurements was adopted. The blood samples were obtained in the morning from subjects after fasting for at least 8 h and transported to a clinical laboratory . The blood samples were examined within 8 h to measure fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).The diagnosis of hyperlipidemia was based on the criteria of the “Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults”: TC ≥ 5.18 mmol/L or TG ≥ 1.70 mmol/L or HDL-C < 1.04 mmol/L or LDL-C ≥ 3.37 mmol/L or previous diagnosis of hyperlipidemia by a physician . AccordiP < 0.05 was considered statistically significant. Data analyses were conducted using SPSS 22.0 .Descriptive data analyses were conducted. Frequency distribution was used to present the subjects' characteristics, and the prevalence of stroke risk factors were reported using percentages. The chi-squared test was used to compare the prevalence of stroke risk factors in different age groups. The result of the trend test was analyzed using linear-by-linear association. Cramer's V or Gamma was used to indicate the relationship between the participants' characteristics and the number of key stroke risk factors. Multiple regression analyses were used to explore the adjusted association between the participants' characteristics and the number of key stroke risk factors. All tests were two-tailed, and A total of 4,052 participants aged 40 years or older were eventually included in this study. The mean age of the participants was 54.85 ± 9.30, 40.0% were male, and 51.0% were urban residents. Supplementary Table p-values were all < 0.001.The prevalence of hypertension and diabetes were the highest in the 70~ year-old group, while hyperlipidemia was highest in the 60- to 69-year-old group Table . The lowTable Figures This population-based cross-sectional study was the first investigation of stroke and its risk factors in Dehui City in Jilin province, China. As the prevalence and incidence of stroke were significantly increased after 39 years of age, the included participants were over 39 . CompareThe results showed that the prevalence of hypertension, hyperlipidemia, and diabetes had a tendency to increase with age. Studies indicated that advanced age was a risk factor for hypertension, hyperlipidemia, and diabetes, consistent with our findings –18. HighA total of 84.1% of the participants in this study had one or more of the four risk factors for stroke which implied that most people over 40 years of age in Dehui City were exposed to the risk of stroke. The risk of accumulating stroke risk factors for males was higher than females. The possible explanation was that the prevalence of overweight or obesity and hypertension were higher in male than in female in this district, but there was no difference in the prevalence of dyslipidemia and diabetes between different sexes , 22–24. Our study has some potential limitations. Part of the results were based on self-reported data and the recall bias could not be avoided. In addition, the participants were recruited from Dehui City of Jilin province, China, and the conclusion cannot represent the other places in Jilin province. Finally, those who were ill or too weak to complete the interview were not included in our survey.Special attention should be paid to male or patients with family history of cerebrovascular disease in the primary prevention of stroke. Regular examination of blood pressure, blood fat, blood sugar, and BMI and effective control could reduce their risk of stroke. Health education should be carried out to encourage residents to take salt less diet and regular physical exercise in Dehui City. Although smoking is a protective factor for the accumulation of key stroke risk factors, it is also an important risk factor for many kinds of diseases. So smoking cessation is still crucial to the health of residents.In conclusion, there was a high prevalence of certain key stroke risk factors among older adults in our study. Male, partially salty diets, and family history of cerebrovascular diseases were risk factors for the accumulating of certain stroke risk factors while regular physical exercise was a protective factor.YY and Z-NG handled the conception and design. F-LZ, H-JS, and XS acquired the data. PZ performed the analysis. PZ and HJ drafted the manuscript. Z-NG and YY performed a critical revision.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.


Introduction: Diabetes mellitus is an emerging public health concern. The aim of this study was to assess the gender-specific knowledge of patients about diabetes mellitus, its complications, and its management.Methods: A cross-sectional study was conducted in outpatient clinics of Faisalabad, Pakistan, from November 2017 to March 2018. Consecutive patients with diabetes, aged >18 years, were administered a validated questionnaire related to knowledge of diabetes, its complications, and its management. An analysis was conducted using IBM SPSS Statistics for Windows, Version 19.0 software . Results were stratified on the basis of gender and were compared using chi-square tests.Results: Of the 840 patients recruited, 76.4% were aged >50 years. About 57% were women, and 43% were men. Most men (89.4%) and women (91.7%) were aware that the management of diabetes requires a cutting down in the consumption of refined sugar, and 64.6% and 50.4%, respectively, reported that they exercise regularly to control their glucose levels. Moreover, 14% of the men and 25% of the women responded that they knew neuropathy is a complication of diabetes.Conclusion: Diabetes mellitus has debilitating effects on patients and communities. To effectively manage diabetes and to delay the development of complications, there is a dire need to educate patients, families, and communities. Diabetes mellitus (DM) is an emerging public health concern with multiple complications and an alarmingly increasing prevalence worldwide, especially in the Middle East and South Asia . The IntThe Diabetes Prevalence Survey of Pakistan 2016-17 revealed that 16.98% of the total population had DM -6. In coTo decrease the prevalence of this disease, prevention strategies are imperative. Awareness regarding risk factors, such as lifestyle modification and exercise, is crucial -9. StudiThe objective of this study was to assess the gender-specific knowledge about DM, its complications, and management in Pakistan. The findings of this study could help in designing effective gender-specific educational programs for the prevention of this disease.A descriptive cross-sectional study was conducted in the outpatient clinics (OPDs) in Faisalabad, Pakistan from November 2017 to March 2018. Included in this study were diabetic patients aged >18 years who visited the OPDs of the selected family medicine clinics and those who consented to participate in the study. Patients with serious co-morbidities, including cancer or cardiac, respiratory, renal, or liver failure, were excluded. A total of 840 patients were recruited using a non-probability consecutive sampling technique.The validated questionnaire consisted of three sections: demographic characteristics, knowledge of diabetes, and patients’ self-care management of diabetes; most questions had binary responses (yes/no). Data collectors were trained for obtaining consent and getting the forms filled up.Written informed consent was obtained from all eligible participants, with patient confidentiality maintained during data collection. The study was conducted in accordance with the code and ethics of the Declaration of Helsinki.Data were entered and analyzed using IBM SPSS Statistics for Windows, Version 19.0 software . Categorical data were reported as frequencies and proportions. Results were stratified on the basis of gender and were compared using chi-square tests. A p-value <0.05 was considered statistically significant.Of the 900 eligible participants who were invited to participate in the study, 840 (93%) provided consent and were included in the final analysis. About 57% were women and 43% were men. Of the study subjects, 76.4% of the patients were aged >50 years, 21% had no formal education, and 21% had completed matriculation. Most of the patients (90.1%) were married, and 50% reported having other co-morbidities (Table Table Table Figure Figure The proper management of DM is challenging, especially for people living in developing countries, due to the lack of access and the affordability of health care services. The IDF and American Diabetes Association have stressed the importance of clinical care, self-care practices, and patient education in the management and prevention of complications associated with DM -16. ThesThe current study found no major differences between men and women regarding their basic knowledge of DM and its management. In contrast, previous studies found that men were significantly less knowledgeable about diabetes than women -21. In tThe current study reveals that most patients were aware that an unhealthy diet and refined sugar are risk factors for complications of DM. These results are similar to those reported by a population-based study in Pelotas, South Brazil .Physical activity can also reduce the likelihood of the complications of DM. A quasi-experimental study in 65 patients with type 2 DM reported that an exercise regime longer than 12 weeks was associated with reductions in glycosylated hemoglobin levels in diabetic patients . Our stuThe complications of diabetes are associated with morbidity, mortality, and increased health care costs . PatientThe study had certain limitations. This was a descriptive cross-sectional study so there is a need for longitudinal studies to assess temporal associations between gender and knowledge of diabetes. Moreover, a reporting bias could have occurred in this study as we relied on the self-reporting of the patients about the co-morbidities and complications of diabetes. This may have over-estimated or under-estimated the study results. We also did not ask participants regarding the optimum level of glycemic control, which could have given us more information about their knowledge regarding DM. Additionally, it will be interesting to see a comparison between urban and rural areas of Pakistan so that a community-based diabetes awareness program could be implemented on a national scale.Diabetes mellitus has one of the most debilitating effects on the patient and the community owing to the disease itself and its complications. We found that though there was not a notable difference in the knowledge levels of the male and female population except for one or two aspects of diabetes, there are many patients who lack awareness and basic knowledge of the complications of this disease.In order to manage DM effectively and to delay the development of complications, there is a need to educate the patient, family, and community. The health care providers should organize health education sessions to provide early diabetic education regarding causes, self- management, lifestyle modifications, and preventive measures for diabetic complications. This could help in diabetes management and will, in turn, improve the quality of life of the patients. Moreover, the formation of a diabetes support group can also be very beneficial for the patient and their families. This study also found that some patients were following good practices. Such patients should be kept motivated so that they may continue their health routine and can become a source of inspiration to other patients.


Anxiety disorders are one of the most diagnosed mental health disorders. Common treatment consists of cognitive behavioral therapy and pharmacotherapy. In clinical practice, also art therapy is additionally provided to patients with anxiety (disorders), among others because treatment as usual is not sufficiently effective for a large group of patients. There is no clarity on the effectiveness of art therapy (AT) on the reduction of anxiety symptoms in adults and there is no overview of the intervention characteristics and working mechanisms.A systematic review of (non-)randomised controlled trials on AT for anxiety in adults to evaluate the effects on anxiety symptom severity and to explore intervention characteristics, benefitting populations and working mechanisms. Thirteen databases and two journals were searched for the period 1997 –October 2017. The study was registered at PROSPERO (CRD42017080733) and performed according to the Cochrane recommendations. PRISMA Guidelines were used for reporting.Only three publications out of 776 hits from the search fulfilled the inclusion criteria: three RCTs with 162 patients in total. All studies have a high risk of bias. Study populations were: students with PTSD symptoms, students with exam anxiety and prisoners with prelease anxiety. Visual art techniques varied: trauma-related mandala design, collage making, free painting, clay work, still life drawing and house-tree-person drawing. There is some evidence of effectiveness of AT for pre-exam anxiety in undergraduate students. AT is possibly effective in reducing pre-release anxiety in prisoners. The AT characteristics varied and narrative synthesis led to hypothesized working mechanisms of AT: induce relaxation; gain access to unconscious traumatic memories, thereby creating possibilities to investigate cognitions; and improve emotion regulation.Effectiveness of AT on anxiety has hardly been studied, so no strong conclusions can be drawn. This emphasizes the need for high quality trials studying the effectiveness of AT on anxiety. The focus is on the process of creating and (associated) experiencing, aiming for facilitating the expression of memories, feelings and emotions, improvement of self-reflection and the development and practice of new coping skills , 23, 24.AT is believed to support patients with anxiety in coping with their symptoms and to improve their quality of life . Based oAlthough AT is often indicated in anxiety, its effectiveness has hardly been studied yet. In the last decade some systematic reviews on AT were published. These reviews covered several areas. Some of the reviews focussed on PTSD –34, or hNo review specifically aimed at the effectiveness of AT on anxiety or on specific anxiety disorders. For anxiety as the primary condition, thus not related to another primary disease or condition (e.g. cancer or autism), there is no clarity on the evidence nor of the employed therapeutic methods of AT for anxiety in adults. Furthermore, clearly scientifically substantiated working mechanism(s), explaining the anticipated effectiveness of the therapy, are lacking.The primary objective is to examine the effectiveness of AT in reducing anxiety symptoms.The secondary objective is to get an overview of (1) the characteristics of patient populations for which art therapy is or may be beneficial, (2) the specific form of ATs employed and (3) reported and hypothesized working mechanisms.The systematic review was performed according to the recommendations of the Cochrane Collaboration for study identification, selection, data extraction, quality appraisal and analysis of the data . The PRIThe review included peer reviewed published randomised controlled trials (RCTs) and non-randomised controlled trials (nRCTs) on the treatment of anxiety symptoms. nRCTs were also included because it was hypothesized that nRCTs are more executed than RCTs, for the research field of AT is still in its infancy.Only publications in English, Dutch or German were included. These language restrictions were set because the reviewers were only fluent in these three languages.Studies of adults (18–65 years), from any ethnicity or gender were included.AT provided to individuals or groups, without limitations on duration and number of sessions were included.The following control groups were included: 1) inactive treatment  and 2) active treatment (standard care or any other treatment). Co-interventions were allowed, but only if the additional effect of AT on anxiety symptom severity was measured.Included were studies that had reduction of anxiety symptoms as the primary outcome measure. Excluded were studies where reduction of anxiety symptoms was assessed in non-anxiety disorders or diseases and studies where anxiety symptoms were artificially induced in healthy populations. Populations with PTSD were not excluded, since this used to be an anxiety disorder until 2013 .The following 13 databases and two journals were searched: PUBMED, Embase (Ovid), EMCare (Ovid), PsychINFO (EBSCO), The Cochrane Library  for the electronic databases according to their specific subject headings or structure. For each database, search terms were adapted according to the search capabilities of that database . In the first phase, titles were screened for eligibility. The abstracts of the remaining entries were screened and only those that met the inclusion criteria were selected for full text appraisal. These full texts were subsequently assessed according to the eligibility criteria. Any disagreement in study selection between the two independent reviewers was resolved through discussion or by consultation of a third reviewer (EB).The data were extracted by using a data extraction spreadsheet, based on the Cochrane Collaboration Data Collection Form for intervention reviews , control description, outcome domains and outcome measures, time points, outcomes and statistics.After separate extraction of the data, the results of the two independent assessors were compared and discussed to reach consensus.The risk of bias (RoB) was independently assessed by the two reviewers with the Cochrane Collaboration’s tool for assessing RoB . Bias waA summary assessment of RoB for each study was based on the approach of Higgins & Green : overallThe primary outcome measure was anxiety symptoms reduction (pre-post treatment). The outcomes are presented in terms of differences between intervention and control groups . Within-group outcomes are also presented, to identify promising outcomes and hypotheses for future research.2 statistic and performing the Chi2 test. If heterogeneity was considered relevant, e.g. I2 statistic greater than 0.50 and p<0.10, sources of heterogeneity were investigated, subanalyses were performed as deemed clinically relevant, and subtotals only, or single trial results were reported. In case of a meta-analysis, publication bias was assessed by drawing a funnel plot based on the primary outcome from all trials and statistical analysis of risk ratios or odds ratios as the measure of treatment effect.Data from studies were combined in a meta-analyses to estimate overall effect sizes, if at least two studies with comparable study populations and treatment were available that assessed the same specific outcomes. Heterogeneity was examined by calculating the IA content analysis was conducted on the characteristics of the employed ATs, the target populations and the reported or hypothesized working mechanisms.Quality (or certainty) of evidence of the studies with significant outcomes only was was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) . EvidencThe search yielded 776 unique citations. Based on title and abstract, 760 citations were excluded because the language was not English, Dutch or German (n = 23), were not about anxiety (n = 164), or it concerned anxiety related to another primary disease or condition (n = 175), didn’t concern adults (18–65 years) (n = 152), were not about AT (n = 94), were not a controlled trial (n = 131), or were lacking a control group (n = 22) or anxiety symptoms were not used as outcome measure (n = 1).Excluded studies with reasons for exclusion. Finally, three studies were included for the systematic review , of which 27 publications were eligible for abstract screening and were other than the 938 citations found in the search described above (see Study selection). From these abstracts, 18 were excluded because they were not peer reviewed (n = 3), not in English, Dutch or German (n = 1), not about anxiety (n = 2), or were about anxiety related to cancer (n = 2), were not about AT (n = 2) or were not a controlled trial (n = 8). Nine full texts were screened for eligibility and were all excluded. Six full texts were excluded because these concerned psychodynamic therapies and did not include AT –68. Two The review includes three RCTs. The study populations of the included studies are: students with PTSD symptoms and two groups of adults with fear for a specific situation: students prior to exams and prisoners prior to release. The trials have small to moderate sample sizes, ranging from 36 to 69. The total number of patients in the included studies is 162 .In one study, AT is combined with another treatment: a group interview . The othThe provided AT varies considerably: mandala creation in which the trauma is represented  or colouSee Based on the Cochrane Collaboration’s tool for assessing risk of bias, estimations of bias were made. Selection bias: overall, methods of randomization were not always described and selection bias can therefore not be ruled out, which leads to unclear RoB. Henderson et al. [n et al.  describen et al.  did not n et al.  did not Performance bias: Sandmire’s RCT had inactive control, which gives a high risk on performance bias [nce bias . Like innce bias , 73. It Detection bias: in all studies only self-report questionnaires were used. The questionnaires used are all validated, which allows a low risk score of response bias. However, the exact circumstances under which measures are used are not described [escribed , 71 and escribed ), which Attrition bias: in the study of Henderson it is not clear whether the outcome dataset is complete.Reporting bias: there are no reasons to expect that there has been selective reporting in the studies.Other issues: in Sandmire et al. [e et al.  it was nOverall risk of bias: since all studies had one or more domains with high RoB, the overall RoB was high.The measures used in the studies are shown in p = 0.001) and on trait anxiety ): 39.1 (5.8) - 33.3 (6.1); control group (mean (SD)): 38.2 (10.2) - 37.3 (11.2); p = 0.004) There were no significant differences in effectiveness between the five types of art making activities.Sandmire et al.  showed sp-value: not reported) immediately after treatment. At follow-up after one month there was also no significant effect of creating mandalas on anxiety symptoms: experimental group (mean (SD): 40.95 (11.54); control group (mean (SD): 42.0 (13.26)), but there was significant improvement of PTSD symptom severity at one-month follow-up (p = 0.015).Henderson et al.  reportedp = 0.004). The anxiety level in the control group on the other hand, who received only group interview, increased between pre- and post-treatment (HAM-A (mean (SD): 24.75 (6.14) - 25.22 (7.37), not significant; SAS (mean (SD): 62.57 (7.36) - 66.11 (10.41), p = 0.33).Yu et al. (2016) did not report analyses of between-group effects. Only the experimental group, who made HTP drawings followed by group interview, showed a significant pre- versus post-treatment reduction of anxiety symptoms (two-tailed paired sample t-tests: HAM-A (mean (SD): 24.36 (9.11) - 17.42 (10.42), p = 0.001; SAS (mean (SD): 62.63 (9.46) - 56.78  Of three included RCTs studying the effects of AT on reducing anxiety symptoms, one RCT  showed aRegarding within-group differences, two studies , 72 showThe quality of the evidence in Sandmire  as assesBecause data were insufficiently comparable between the included studies due to variation in study populations, control treatments, the type of AT employed and the use of different measures, a meta-analysis was not performed.AT seems to be effective in the treatment of pre-exam anxiety  in adult liberal art students , althougSandmire et al.  gave stuYu et al.  used theHenderson et al.  treated Sandmire used a single administration of art making to treat the handling of stressful situations  of undergraduate liberal art students. The art intervention did not explicitly expose students to the source of stress, hence a general working mechanism of AT is expected. The authors claim that art making offers a bottom-up approach to reduce anxiety. Art making, in a non-verbal, tactile and visual manner, helps entering a flow-like-state of mind that can reduce anxiety , comparaYu reports that nonverbal symbolic methods, like HTP-drawing, are thought to reflect subconscious self-relevant information. The process of art making and reflection upon the art may lead to insights in emotions and (wrong) cognitions that can be addressed during counseling. The authors state that “HTP-drawing is a natural, easy mental intervention technique through which counselors can guide prisoners to form helpful cognitions and behaviors within a relative relaxing and well-protected psychological environment”. In this case the artwork is seen as a form of unconscious self-expression that opens up possibilities for verbal reflections and counseling. In the process of drawing, the counselor gives guidance so the drawing becomes more complete and enriched, what possibly entails a positive change in the prisoners’ cognitive patters and behavior.Henderson treated PTSD symptoms in students and expected the therapy to work on anxiety symptoms as well. The AT intervention focussed on the creative expression of traumatic memories, which can been seen as an indirect approach to exposure, with active engagement. The authors indicate that mandala creation (related to trauma) leads to changes in cognition, facilitating increasing gains. Exposure, recall and emotional distancing may be important attributes to recovery.Summarizing, three different types of AT can be distinguised: 1) using art-making as a pleasant and relaxing activity; 2) using art-making for expression of (unconsious) cognitive patterns, as an insightful tool; and 3) using the art-making process as a consious expression of difficult emotions and (traumatic) memories.Based on these findings, we can hypothesize that AT may contribute to reducing anxiety symptom severity, because AT may:induce relaxation, by stimulating a flow-like state of mind, presumably leading to a reduction of cortisol levels and hence stress and anxiety reduction (stress regulation) ;make the unconscious visible and thereby creating possibilities to investigate emotions and cognitions, contributing to cognitive regulation , 72.create a safe environment for the conscious expression of (difficult) emotions and memories, what is similar to exposure, recall and emotional distancing, possibly leading to better emotion regulation .Currently there is no overview of evidence of effectiveness of AT on the reduction of anxiety symptoms and no overview of the intervention characteristics, the populations that might benefit from this treatment and the described and/ or hypothesized working mechanisms. Therefore, a systematic review was performed on RCTs and nRCTs, focusing on the effectiveness of AT in the treatment of anxiety in adults.Three publications out of 776 hits of the search met all inclusion and exclusion criteria. No supplemented publications from the reference lists (999 titles) of 15 systematic reviews on AT could be included. Considering the small amount of studies, we can conclude that effectiveness research on AT for anxiety in adults is in a beginning state and is developing.The included studies have a high risk of bias, small to moderate sample sizes and in total a very small number of patients (n = 162). As a result, there is no moderate or high quality evidence of the effectiveness of AT on reducing anxiety symptom severity. Low to very low-quality of evidence is shown for AT for pre-exam anxiety in undergraduate students . One RCTThe strength of this review is firstly that it is the first systematic review on AT for primary anxiety symptoms. Secondly, its quality, because the Cochrane systematic review methodology was followed, the study protocol was registered before start of the review at PROSPERO, the AMSTAR 2 checklist was used to assess and improve the quality of the review and the results were reported according to the PRISMA guidelines. A third strength is that the search strategy covers a long period of 20 years and a large number of databases (13) and two journals.art therapy in case the visual arts were used to promote health/wellbeing and/or the author called it art therapy. Thus, only art making as an artistic activity was excluded. This may have led to unwanted exclusion of interesting papers.A first limitation, according to assessment with the AMSTAR 2 checklist, is that only peer reviewed publications were included, which entails that many but not all data sources were included in the searches. Not included were searches in trial/study registries and in grey literature, since peer reviewed publication was an inclusion criterion. Content experts in the field were also not consulted. Secondly, only three RCTs met the inclusion criteria, each with a different target population: students with moderate PTSD, students with pre-exam anxiety and prisoners with pre-release anxiety. This means that only a small part of the populations of adults with anxiety (disorders) could be studied in this review. A third (possible) limitation concerns the restrictions regarding the included languages and search period applied (1997- October 2017). With respect to the latter it can be said that all included studies are published after 2006, making it likely that the restriction in search period has not influenced the outcome of this review. No studies from 1997 to 2007 met the inclusion and exclusion criteria. This might indicate that (n)RCTs in the field of AT, aimed at anxiety, are relatively new. A fourth limitation is the definition of AT that was used. There are many definitions for AT and discussions about the nature of AT (e.g. ). We conA fifth limitation is the use of the GRADE approach to assess the quality of evidence of art therapy studies. This tool is developed for judging quality of evidence of studies on pharmacological treatments, in which blinding is feasible and larger sample sizes are accustomed. However the assessed study was a RCT on art therapy , in whicThe results of the review are in agreement with other findings in the scientific literature on AT demonstrating on the one hand promising results of AT and on the other hand showing many methodological weaknesses of AT trials. For example, other systematic reviews on AT also report on promising results for art therapy for PTSD –34, 37 aThree approaches in AT were identified in this review: 1) using art-making as a relaxing activity, leading to stress reduction; 2) using the art-making process as a consious pathway to difficult emotions and (traumatic) memories; leading to better emotion regulation; and 3) using art-making for expression, to gain insight in (unconscious) cognitive patterns; leading to better cognitive regulation.Art-as-therapy focuses on the healing ability and relaxing qualities of the art process itself and was first described by Kramer in 1971 [These three approaches can be linked to two major directions in art therapy, identified by Holmqvist & Persson : “art-as in 1971 . This ca in 1971 . A possi in 1971  due to tArt-in-psychotherapy, first described by Naumberg [Naumberg  encompasNaumberg , so whatNaumberg , which iThe overall picture of the described and hypothesized working mechanisms that emerged in this review lead to the hypotheses that anxiety symptoms may decrease because AT may support stress regulation , more robust studies are needed.Besides anxiety symptoms, the effectiveness of AT on aspects of self-regulation like emotion regulation, cognitive regulation and stress regulation should be further studied as well. By evaluating the changes that may occur in the different areas of self-regulation, better hypotheses can be generated with respect to the working mechanisms of AT in the treatment of anxiety.A key point for AT researchers in developing, executing and reporting on RCTs, is the issue of risk of bias. It is recommended to address more specifically how RoB was minimalized in the design and execution of the study. This can lower the RoB and therefor enhance the quality of the evidence, as judged by reviewers. One of the scientific challenges here is how to assess performance bias in AT reviews. Since blinding of therapists and patients in AT is impossible, and if performance bias is only considered by ‘lack of blinding of patients and personnel’, every trial on art therapy will have a high risk on performance bias, making the overall RoB high. This implies that high or even medium quality of evidence can never be reached for this intervention, even when all other aspects of the study are of high quality. Behavioral interventions, like psychotherapy and other complex interventions, face the same challenge. In 2017, Munder & Barth  publisheThe effectiveness of AT on reducing anxiety symptoms severity has hardly been studied in RCTs and nRCTs. There is low-quality to very low-quality evidence of effectiveness of AT for pre-exam anxiety in undergraduate students. AT may also be effective in reducing pre-release anxiety in prisoners.The included RCTs demonstrate a wide variety in AT characteristics . The described or hypothesized working mechanisms of art making are: induction of relaxation; working on emotion regulation by creating the safe condition for conscious expression and exploration of difficult emotions, memories and trauma; and working on cognitive regulation by using the art process to open up possibilities to investigate and (positively) change (unconscious) cognitions, beliefs and thoughts.High quality trials studying effectiveness on anxiety and mediating working mechanisms of AT are currently lacking for all anxiety disorders and for people with anxiety in specific situations.S1 Checklist(PDF)Click here for additional data file.S1 File(PDF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.


To systematically review the literature on the metabolic costs of activities of daily living (ADL) in persons with a lower limb amputation (LLA).th, 2017.A literature search was undertaken in the Pubmed, Embase, CINAHL, CENTRAL, and PsycINFO databases using keywords and synonyms for LLA, metabolic costs, and ADL. The last search was performed on November 29Studies were included if they met the following 2 criteria: participants were adults with a  LLA and metabolic costs were measured while participants performed a physical activity or ADL.2/kg/min) and heart rate (beats/min) increased with a higher walking speed and a more proximal amputation. Additionally, oxygen consumption was determined by the interaction terms walking speed x amputation level and walking speed squared. Heart rate was determined by the interaction term walking speed squared.Data of 1,912 participants from 61 studies were included in the systematic review and meta-analysis. The studies used different terms to describe metabolic costs. Participants were recruited in different settings, relatively healthy, with few comorbidities. Limited data were available on metabolic costs of other activities than walking with a prosthesis. A linear mixed model analysis was performed based on the means reported, with study as unit of analysis and test results of different groups and measurement conditions as repeated measures within the unit of analysis. Predictors entered in the analysis were e.g. level and reason of amputation, age, weight, and height. During walking, oxygen consumption (ml O2/kg/min) and heart rate (beats/min) increased with a higher walking speed and a more proximal amputation. Data on metabolic costs of other activities were limited. The poor quality of the studies and the relatively healthy participants limited generalizability of the results of the meta-analysis.During walking, oxygen consumption (ml O In rehabilitation medicine, the main goals for persons with a lower limb amputation (LLA) are walking with a prosthesis and regaining functional capacity with regard to activities of daily living (ADL) –3. To be2max test is the criterion measure of aerobic capacity, and it is a valid predictor of cardiorespiratory capacity [2max in persons with a LLA. Furthermore, these studies used different test protocols [2max in participants with a LLA compared with controls. These differences are probably due to deconditioning or comorbidities.In the Netherlands, more than 90% of LLAs are due to vascular disease and/or diabetes mellitus (DM) ,7. In thcapacity . To daterotocols ,15,16. TA previous systematic review looked at the influence of physical capacity on regaining the ability to walk (with a prosthesis) . No suff2peak [One study reported the relative aerobic load of walking, measured as a percentage of the VO2peak . The rel2peak .For the general population, the metabolic costs of ADL are well reported in the compendium of physical activities, the so called Metabolic Equivalent of Task (MET)-values . HoweverThe specific aims of this systematic review and meta-analysis are 1) to analyse what is known about the metabolic costs of different ADL in participants with a LLA; 2) to explore which methods and outcome measures are used to evaluate these metabolic costs; and 3) to determine whether metabolic costs are influenced by level of amputation, reason for amputation, and walking speed.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used for conducting this systematic review and meta-analysis .https://www.crd.york.ac.uk/PROSPERO/#index.php, CRD42016050990).The protocol for this systematic review and meta-analysis was registrated at PROSPERO  LLA and metabolic costs were measured while participants performed a physical activity or ADL. Editorials, (expert) opinions, comments, reviews, and off- topic studies were excluded. Studies on toe or midfoot amputations, amputations other than a lower extremity, or endoprostheses were also excluded, as were studies with children or animals and model studies.Quality assessment was independently performed by two reviewers  using the Agency for Healthcare Research and Quality (ARHQ) methodology checklist . AdditioStatistical analyses were performed using IBM SPSS Statistics 23. Descriptive statistics (mean and standard deviation) were calculated for study variables. Initially, effect sizes were calculated based on study data. For oxygen consumption one study, however, reported uncommonly small standard deviations relative to other studies, resulting in extremely large effect sizes . The aut2/kg/min) was analysed using the following potential predictors: level of amputation, reason for amputation, age, weight, height, and walking speed. Only studies that reported oxygen consumption (ml O2/kg/min) were selected. When possible, outcomes were converted to ml/kg/min. If this was not possible based on the reported data within the study, the study was excluded for the analysis. Potential predictors were entered into the linear mixed model analysis. If the model fit (-2LL statistic) increased significantly, the predictors remained in the model. Cause of amputation was categorized in trauma and vascular, level of amputation as below knee and above knee. Studies with mixed groups  were excluded from the analysis.The outcome oxygen consumption  were heterogeneous. The mean (SD) number of participants was 13.5 (13.2). The groups ranged from 10 to 101, and subgroups ranged from 3 to 44. There were different reasons for amputation and/or levels of amputation. Time since amputation ranged from 68 days to 27 years . The majOne study referredAgreement for the quality assessment was 93% (Cohen’s kappa: 0.89). The mean quality score was 6.6, ranging from 3 to 10 points out of 14 possible points . In 43 o2/kg/min) and heart rate (beats/min) were the most frequently reported outcome measures of metabolic costs in 39 and 36 studies, respectively  were found: level of amputation, walking speed, and the interaction terms walking speed squared and walking speed x amputation level  were found to be significant , Table 42/kg/min) was influenced by amputation level, walking speed, and the interaction terms walking speed squared and walking speed x amputation level. Multiple previous studies reported that higher metabolic costs are associated with a more proximal level of amputation [2/kg/min vs. 18.9±1.8 ml O2/kg/min). In the multilevel analysis an interaction effect between walking speed squared and group was found, indicating that the effect of walking speed squared was not the same for groups. This interaction effect can be related to amputation level, but also to differences between studies including differences in methodology i.e. measurement procedures, general health, body weight, height, physical condition, and or age of the participants. However source studies report too inconsistently to be able to include these confounders in the regression analyses. The curve is based on the regression coefficients of the linear mixed model analysis of the reported means in the studies. Different study designs and heterogeneity in study populations may influence the reported means and therefore the regression curve.Sixty-one studies  were included in this systematic review and meta-analysis. A linear mixed model was used to analyse the data. It was found that reported mean oxygen consumption ) of walking in participants with a traumatic LLA at SSWS were equal to those of controls, whereas the SSWS of the LLA group was slower than that of the control group [One of the most noteworthy findings was that reason of amputation was not a predictor in the multilevel analysis, which may be related to the limited number of studies analysing participants with a vascular amputation. Additionally, many studies did not report on reason of amputation, had a mixed group of reasons of amputation, without specifying outcomes for separate groups. When adding reason of amputation to the mixed model analysis, 4 studies were excluded and coefficients were not significant. However, some previous studies report higher metabolic costs for walking in participants with a dysvascular amputation . One stuol group . In the ol group . Howeverol group ,58.2max, because in most of the settings equipment for measuring oxygen consumption and/or VO2max is not available. Furthermore, it is questionable whether heart rate is a good predictor of metabolic costs in persons with an amputation due to vascular disease and/or DM, because they often have comorbidities such as cardiovascular disease and are likely to use medication that influences their heart rate. Significant predictors of heart rate as an outcome measure were walking speed, amputation level, and walking speed squared. Reason for amputation was not a significant predictor of heart rate.The other frequently used outcome measure of metabolic costs was heart rate (beats/min). Studies reported heart rate were not all the same studies included in the analysis for oxygen consumption. Therefore, a different study population is analysed , with a 2max-test is seen as the criterion measure of physical and aerobic capacity. Only a few studies [2max in participants with a LLA. Only one study reported the relative aerobic load of walking, measured as a percentage of the VO2peak [2max may be used as an indicator for walking ability and for  training in persons with a LLA. Additionally, it is relevant to know an individual’s aerobic capacity in combination with the metabolic costs of daily activities, to be able to evaluate the individual strain of ADL. Possible explanations for the lack of VO2max-testing in persons with a LLA are comorbidities, lack of knowledge of this type of testing, lack of knowledge of the interpretation of the test results, costs, and lack of facilities.As stated previously, the VO studies ,16,62,69 VO2peak . For wal VO2peak . TherefoPrevious systematic reviews did not primarily aim to analyse metabolic costs of ADL in participants with a LLA ,18. They2/kg/min) and heart rate for walking in high grass, no significant differences for the other 2 conditions were found. As previously mentioned, the rehabilitation of persons with a LLA is not only aimed at walking with prosthesis, but also at regaining functional capacity and independency with regard to ADL. However, limited data are available on metabolic costs of other activities than walking with a prosthesis.Of the included 61 studies, 3 studies reported on metabolic costs for walking stairs ,30,80. OThe results of this systematic review and meta-analysis were dependent on the quality of research of the available studies. The included studies reported poorly on details of the study populations and potential predictors of metabolic costs in participants with a LLA. Because of the heterogeneity and the limited reporting, the mixed model analysis was performed with reported means, with study as unit of analysis. Furthermore, the studies included relatively healthy participants and, as mentioned before, data on metabolic costs for other ADL than walking is very limited.Further research on the metabolic costs of walking, and daily activities in persons with a LLA is relevant in order to gather data that will help with setting functional goals, optimizing individual training, and evaluating LLA-rehabilitation. Study populations and subgroups should be described with sufficient detail regarding reason for amputation, age, gender, and level of amputation to improve generalizability. The inclusion of participants with different levels of amputation in a mixed group should be avoided.From a clinical perspective, it is important to assess the metabolic costs of ADL and the physical capacity of persons with a LLA in order to optimize their rehabilitation program, train them at an optimal walking speed, improve their potential to walk with a prosthesis, and help them regain functional capacity with regard to ADL.In general oxygen consumption and heart rate for persons with transtibial and transfemoral amputation while walking are higher than for controls. A higher walking speed is associated with a higher oxygen consumption and this increase was stronger for persons with a transfemoral amputation compared to controls. Source studies report inconsistently, therefore it is not possible to include other possible confounders in the analyses such as age and cause of amputation.Limited information is available on metabolic costs of other activities than walking. The quality of the included studies was low; therefore, the results of this systematic review should be regarded with some caution.S1 TableY yes, N no, N.A. not applicable, ? not specified/unknown. *1. Was the source of information for the reported outcome measurements mentioned? 2.Were inclusion criteria reported? 3. Were exclusion criteria reported? 4. Was the timeframe of recruitment reported? 5. Were subjects consecutively recruited or population-based? 6. Were evaluators of subjective components masked to other aspects of the subjects? 7. Have any assessments been undertaken for quality assurance purposes (test/retest of primary outcome measurements)? 8. Was the used equipment validated or were there references to validation in previous publications? 9. Were all participants included in the analysis? 10.Was confounding assessed and/or controlled for? 11. Were missing data reported? 12. Were patient response rate and completeness of data collection reported? 13. Were follow-up, incomplete data, or loss to follow-up reported? 14. Was tested walking speed reported?(DOCX)Click here for additional data file.S2 TableHR heart rate; PCI physiological cost index; %HRR % heart rate reserve; RER respiratory exchange ratio; RR respiratory rate; BP blood pressure; METs metabolic equivalent of task; RQ respiratory quotient; EEI energy expenditure index.(DOCX)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(PDF)Click here for additional data file.S4 File(PDF)Click here for additional data file.S5 File(PDF)Click here for additional data file.


Background: Personality impacts life expectancy and comprehensive treatment efficacy for patients with Parkinson's disease (PD). However, current research fails to involve the family caregiver's personality despite significant external support provided by family caregivers. This study explored neuroticism and conscientiousness personality factors of the patient and family caregiver associated with quality of life (QoL) of PD patients.Methods: 134 couples of patients presenting with PD and their family caregivers that met inclusion criteria, were recruited for this cross-sectional study at Shanghai Tenth People's Hospital from October 2015 to 2017. The Parkinson's Disease Questionnaire-39 Items (PDQ-39) for QoL, including the physical component summary (PCS) and mental component summary (MCS), the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI) for neuroticism and conscientiousness personalities, and the Unified Parkinson's Disease Rating Scale (UPDRS) for PD severity questionnaires were employed. Multivariate stepwise linear regression determined the contributions of demographic, clinical and personality variables in PDQ-39, PCS, and MCS.Results: PD patients and neuroticism were significantly associated with total PDQ-39, PCS, and MCS. Additionally, conscientiousness was significantly associated with PDQ-39 and PCS. After adding neuroticism and caregiver conscientiousness personality, the importance of neuroticism for the QoL model dramatically decreased, and caregiver conscientiousness personality was associated with lower scores in total PDQ-39 and PCS.Conclusion: We revealed a significant association between neuroticism and physical or mental status of PD patients; however, this association decreased when caregiver conscientiousness was added to the model. Moreover, conscientiousness of patients and caregivers were associated with improved QoL. Parkinson's disease (PD) is the second most common neurodegenerative in the world that is predominantly characterized by clinical manifestations that include bradykinesia, rigidity, tremor, and postural instability. PD poses a significant burden on the patient's family, not least due to associated costly therapy, but more importantly because PD represents a chronic disease that imparts a serious negative impact on the quality of life (QoL) of the affected patient .The concept of QoL is a comprehensive manifestation of personal well-being, which impacts not only the life expectancy of the patient but also affects the efficacy of comprehensive treatment strategies. Considerable research has focused on how QoL is affected by a variety of physical and psychological factors that include the patient's age, level of education, disease duration, motor function impairment, cognitive deficit, and non-motor syndromes among others –4. MoreoHowever, only a few studies have paid any particular attention to the association between personality and QoL in PD. Dubayova et al. reported that neuroticism might not only coincide with, but also precede the clinically-recognized motor onset seen in PD, and its impact on the QoL in PD patients . In DubaTherefore, an improved understanding of the complex interactions of the patient, the family caregiver's personality and the associated QoL in PD is urgently required. Based on previous evidence of contradictory dominating effects of neuroticism and conscientiousness, we conducted the first survey of the impact of neurotic and conscientious personalities of the patient and family caregiver on the subsequent QoL of patients presenting with PD. In consideration of a high number of informal caregivers, we only investigated the care provided at home, including speaking to the patient's spouse, and their children or intimate relatives, while excluding the professional population of clinical caregivers at the hospital and clinic.This study was approved by the local ethics committee of Shanghai Tenth People's Hospital. In this cross-sectional study, patients with PD were recruited from the movement disorder neurology clinic between October 2015 and 2017 at the Shanghai Tenth People's Hospital affiliated to Tongji University. The interview invitation was sent when the patient visited the movement disorder neurology clinic. Under conditions where the patient and his/her family caregiver agreed to attend the study, the interview was immediately conducted during that visit. Caregivers included any close relative that lived with the patient, whether he/she was a spouse, adult, child, or intimate relative. Patients were assessed by a specialist in PD.Patients that adequately understood the purpose of the study, agreed to participate and signed the informed files.Patients that were diagnosed with idiopathic PD according to the United Kingdom Parkinson's Disease Society Brain Clinical Criteria .Patients that were older than 40 and less than 80 years of age.Patients that had stable anti-Parkinsonian medication for at least 2 weeks.Patients that were at the stage “on.”Patients that had a stable company of at least one family caregiver.Patients that met all of the following inclusion criteria were eligible for the study:A Mini-Mental State Examination (MMSE) score <24 points , 14.Presence of severe infections, cardiopulmonary, cancer, liver or kidney disease or evidence of multisystem functional failure.Presence of mental disorders or serious cognitive dysfunction or history of mental problems and abnormal behavior. During the interview, the National Institute of Neurological Disorders and Stroke-National Institute of Mental Health (NINDS-NIMH)  for psycAll the caregivers did not have a history of mental problems and abnormal behavior.The QoL of patients with PD was assessed using the Parkinson's Disease Questionnaire−39 Items (PDQ-39) , which iDisease severity was measured by the Unified Parkinson's Disease Rating Scale (UPDRS) . UPDRS iExtraversion Openness Five-Factor Inventory (NEO-FFI)  includesSD) or N (%)]. In the context of the PDQ-39 total score, and then with PCS and MCS as the outcome (dependent) variables, multivariate stepwise linear regression analysis with a forward selection of demographic, clinical and personality scores was used as independent variables across three models. The first model included gender, age, disease duration, and the UPDRS score. In the second model, patient neuroticism and conscientiousness were added. The third model also contained variables such as neuroticism and conscientiousness of the caregivers, which was based on model 2. One-way analysis of variance (ANOVA) was used to determine statistical significance of F values for the three models. Level of significance was set at an alpha value of p = 0.05.All statistical analyses were performed with the SPSS version 20.0 statistical software program . The Kolmogorov-Smirnov test was used to investigate the normality of distribution. After the Kolmogorov-Smirnov test, all measurement data were in a normal distribution. Patient characteristics of the study population are presented as descriptive statistics [means , and the UPDRS total score was 46.9 (SD = 18.4), meaning that the majority of patients were not in the early stages of disease progression. When analyzing PDQ-39, besides the total score, we combined the sections for “mobility,” “activities of daily living” and “bodily discomfort”  into the PCS score. The remaining sections were “emotional well-being,” “stigma,” “social support,” “cognition,” and “communication” that were also aggregated together  into the MCS score. From Table SD = 16.7), the PCS was 24.2 (SD = 7.9), 429 which was lower than the MCS .There were no differences seen between non-respondents and participants regarding gender, disease duration, and clinical course of PD. We checked the integrity of the questionnaire data for each patient and the corresponding caregiver in case of missing data. All PD patients took stable anti-parkinsonian therapy according to published international guidelines. Among the 134 patients with PD, the average age was 65.3 years (range 54–79 years); 53.7% of whom were males. The mean duration of PD was 8.4 years  including PCS and MCS data  in PD patients. In addition, longer disease duration (beta = 0.23) was associated with a higher PCS score, and older age of the patient (beta = 0.21) was associated with a higher total PDQ-39 score.R2 = 0.14), PCS (Δadjusted R2 = 0.12) and MCS (Δadjusted R2 = 0.11) as compared to model 1. Aside from UPDRS, which remained dominantly associated with three domains, the age of the patient remained the significant variable for the total PDQ-39 score. Moreover, neuroticism was significantly associated with a higher PDQ-39 score (beta = 0.27), PCS (beta = 0.22), and MCS (beta = 0.24), and conscientiousness was associated with a lower PCS score (beta = −0.20).When neuroticism and conscientiousness of the patients were included , the predictive strength of the model increased for PDQ-39 (Δadjusted R2) of the variance in general QoL (p < 0.01).When neuroticism and conscientiousness of the caregiver were continued and added , then UPDRS remained significantly associated in general PDQ-39, PCS, and MCS, which means that a worse score for disease severity can lead to a worse QoL state. In addition, the neuroticism of the caregiver was not significantly related to the three domains of QoL, while conscientiousness of the caregiver was added to the predictor of PDQ-39 (beta = −0.22) and PCA (beta = −0.24). Compared to model 2, the partial correlation of patient neuroticism decreased 0.05 in the domain of MCS. Overall, this combination of variables in model 3 predicted 84.0% (adjusted R2) was increased with the introduction of independent variables in three models of the stepwise regression, which means that the predictive strength of the model increased from model 1 to model 3. For the three models of the stepwise regression analysis, we can see that all three models are statistically significant. Moreover, model 3 is the optimal regression model.From Table Our study has demonstrated a significant association between neuroticism and the physical and mental status of PD patients, where regression analysis showed that disease severity was the strongest predictor of impaired QoL and that personality traits played a complementary role in QoL.As expected, most predictors of QoL deterioration reflect demographic and baseline disease characteristics, such as older age and longer duration. Many of these factors have been previously found to be associated with poor QoL in patients with PD , 20.Furthermore, we revealed a significant association between neuroticism and physical or mental status of PD patients. In previously published studies, the association between personality and QoL was explored in PD patients. Positive coping personality was both positively associated with QoL and inversely correlated with the UPDRS –23. SimiMoreover, conscientiousness of patients and caregivers were associated with improved QoL. the association between patient neuroticism with QoL decreased when faced with the corresponding caregiver's high level of consciousness—although there was no doubt that its importance in the context of QoL is important and plays a role. Conscientiousness of both the patient and the caregiver are associated with an improved QoL. As in the NEO-FFI model, neuroticism represents a tendency to be sensitive, sad, guilty, depressed, anger-prone, and nervous, and as such, easily delivers complex and unpleasant emotions in such a way that is unreasonable. By contrast, conscientiousness refers to a dutiful, organized, self-disciplinary characteristic, which is usually always associated with a relatively strict expectation of a set standard of behavioral expectations. A possible reason for this might be that the interaction between the patient and the caregiver implies that when the patient was largely influenced by a neurotic personality, the caregiver's duty and disciplinary predilection could help the patient cope with an attacking episode of PD.Coping with illness is not a solitary process in a family. When one is affected by a PD attack, the family is also affected. Furthermore, family caregivers often take responsibility for providing physical and emotional support to PD patients that have a limited capacity to participate in regular social activities.The prevalence of PD increases with age and this number will double by the year 2030 , 27. SinThe study's main strength is its integration of the patient and caregiver's personality in the study analytics. To our knowledge, a new point of view has been revealed, which could be helpful in advancing understanding of the potential factors and complexities of QoL.One of the limitations of this study is the recognition that this is a cross-sectional study and does not take into account longitudinal changes in the QoL. Moreover, due to a lack of a gold standard for evaluating the effects of scoring neuroticism and consciousness, the models we have designed must be confirmed by conducting large-sample studies.In conclusion, the integration of the patient and caregiver's personality could be more important than the patient's personality in assessing QoL, which might lead to the provision of a higher quality care and improved functional recovery of the patient presenting with PD. These might lead to the provision of higher quality care and better functional recovery and community support to re-integrate the patient suffering from PD.All data are available without restriction from the corresponding author on reasonable request.XuL and YaZ conceived and designed the study; GM, YT, XiL, YiZ, JY, and AJ performed data analysis; XM wrote the paper.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.