Background: To evaluate the patients with stroke by Functional Independence Measure (FIM) scale, at the times of admission to hospital, discharge, and six-month poststroke, and to determine the level of improvement in patients after rehabilitative procedures.Methods: A total number of 108 patients with stroke entered the study who were admitted to neurology ward. They all received rehabilitation consultation, and occupational and physical therapies were prescribed for them. Finally, their functional status was evaluated by FIM scale.Results: The median (and range) of FIM scores were 86 (15-119), 102 (16-123) and 119 (17-126) at admission, discharge, and after six-month follow-up, respectively. Our observations showed a significant improvement in FIM scores (P < 0.001). About 13, 30, and 76 percent of the patients in individual functional tasks of motor domain and 61, 75, and 86 percent in cognitive domain got the score of 6 or 7  on admission, discharge, and after six months, respectively. There was a reverse correlation between age and FIM improvement and also duration of hospitalization (P = 0.002).Conclusion: The study showed that the FIM is a valid tool for evaluation of patients with stroke, their follow-up and tracking the disease course. Moreover, we concluded that patients with stroke make a significant improvement in their functional status overtime. The exact effect of rehabilitative procedures and comparison with no treatment, must be assessed in separate studies. These complications directly affect subject’s role fulfillment, and finally lead to decreased patient’s quality of life.8 Functional impairment is a common long lasting sequel of central nervous system (CNS) disorders which can cause patient disability.Depending on the involved artery, the size and location of supplied cerebral area and the extent of resulted brain damage, patients might experience various complications. Postural disorders, sensory and motor deficits, hemiplegia or hemiparesis, cognition and comprehension difficulties, memory impairment, decreased self-care and ADL abilities,9 Since most parameters in rehabilitation field are somehow qualitative rather than quantitative, this requirement is even more prominent.One important aspect of clinical research is selecting appropriate measurement tools to quantify the clinical consequences of diseases, effectiveness of applied treatments, and comparison of the results.10Planning an appropriate rehabilitation program for stroke patients needs careful and comprehensive assessment of the subjects and their physical and functional condition. Wide range and chronic nature of CVA complications make this necessary to evaluate several aspects of such patients’ life, including disability, functional impairment, and quality of life. It is important to consider not only short term, but also long lasting consequences. This can provide the health care system with useful information for planning the rehabilitation protocols.4,11 FIM questionnaire was first introduced in 1983. It was presented by American Congress of Rehabilitation Medicine and American Academy of Physical Medicine and Rehabilitation as a promotion of Barthle Index. It is a tool for collection and comparison of rehabilitation outcomes, measurement of patients’ progress, and planning treatment protocols. The producers planned it for more precise evaluation of patients’ functional status, at different stages of disease.4,11 ADL, which are the purpose of this test include: self-care, eating, grooming, bathing, dressing, toileting, swallowing, sphincter control, mobility, transfer, and locomotion. It does not include home management activities.One useful way to estimate the level of functional independence in CVA patients is evaluation of ADL. A valid tool in this field is Functional Independence Measure (FIM).1,4,11The scale contains 18 items, of which 13 items are in physical domains and 5 items are related to cognition. Motor items measure self-care, sphincter control, locomotion, and transfer. Cognitive ones evaluate subject’s communication and social cognition. Based on level of independence, each item is scored from 1 to 7, where 1 indicates total dependence and 7 represents complete independence. Possible scores range from 18 to 126. Obtaining higher score means more independence in ADL FIM score is indicative of patients’ level of disability and the burden of their care.4,12,13 The questionnaire is easy to apply, and takes a fairly short time to be completed .Subjects are routinely evaluated by FIM questionnaire on admission and discharge from rehabilitation setting.The FIM score has not been applied to Iranian population yet, also the validity and reliability of Persian translation is needed to be approved. The purpose of this study was to apply this tool to assess independence level in Iranian patients with stroke. This study can facilitate more extended use of this scale in rehabilitation settings.It was a descriptive observational study. A total number of 108 patients with stroke took part in the study, in whom the stroke diagnosis  was finally confirmed by a neurologist. Subjects were randomly chosen from stroke patients of General Neurology Ward of Shohadaye Tajrish Hospital, Tehran, Iran, in the time interval between January to September 2012. The inclusion criteria were as follows:It was the first stroke attack.Stroke led to functional impairment.Patients were medically and hemodynamically stable.At least one day was passed from the accident.Patients did not take neuroprotective agents.Exclusion criteria included:History of previous stroke.Evidence of transient ischemic attack or subarachnoid hemorrhage.History of orthopedic surgeries, malignancy or neurological disorders such as Alzheimer’s disease.Any other condition with the potency of causing disability and functional impairment.Patient unwilling to join the study.After entering the study, patients’ medical characteristics, including gender, age, type of stroke , duration of hospital admission, and their FIM scores, were all documented. Subjects’ functional status was assessed using FIM questionnaire on admission, discharge, and six months after the incidence of stroke. The evaluations were accomplished by a physical medicine and rehabilitation specialist. On admission and discharge visits, patient were directly observed by a physician, during the task fulfillment, and the level of independence was detected. Since the true bathing situation was not accessible in clinic, we made an exception about this item and asked it orally. In six-month follow-up visit, we made telephone calls and questioned the patients about their condition, and collected data based on their verbal answers.In preliminary visit, after explanation of study process, a written consent was obtained from all eligible patients. Each assessment session took about 30 minutes on average, and all visits were accomplished by the same physician.Patients were admitted by neurology service and referred to rehabilitation specialist by their neurologist. All patients received physical or occupational therapy, during hospital admission. They were also ordered physical and occupational therapies by rehabilitation specialist for the period after discharge, but the rehabilitation program did not happen in a systematic inpatient or outpatient rehabilitation setting.Data analysis was performed using SPSS software . Mean and standard deviation (SD), or median and range (minimum-maximum) were used to present the quantitative scales. For qualitative scales, we obtained the distribution frequency statistics. In order to detect the relations between qualitative scales, the chai-square test was used. We applied Spearman’s rank correlation test to find the linear correlation between two quantitative scales. In order to detect the dependence between changes in quantitative and qualitative scales, the Student’s t-test or Mann-Whitney U test was performed. If the qualitative scale had more than two conditions, the one-way analysis of variance test  was applied. We used LSD (least square deviation) for post-hoc test. Analysis of changes in each subject’s FIM score was accomplished by the Wilcoxon test. Friedman test was also performed to detect the meaningful changes in FIM scores. For predicting the death probability, patients’ characteristics were analyzed by backward multiple logistic regression test.A total number of 108 eligible patients entered the program with documented diagnosis of stroke. All patients were visited by an expert neurologist and the diagnosis of CVA was based on their clinical and imaging findings. In later stages, 29 patients died . Finally, about 73% of the patients (79 subjects) completed the follow-up visits and their data was analyzed. Patients’ characteristics including age, gender, stroke type, and duration of hospitalization are listed in A higher age was found in expired patients group (P < 0.001). Moreover, the mean FIM score of these subjects was lower, at both admission and discharge visits (P < 0.001). Our findings showed that the incidence of death in subjects older than 60 was 11 times and 22 times higher than below 40 and 40-60, respectively. Beside age, the FIM score had an independent effect on the survival rate. It was shown that 10 score increase in initial FIM score resulted in 1.55 times increase in subject’s survival rate. Median, minimum and maximum of FIM scores are shown in As it is evident, the scores of all categories improved over time (P < 0.001). It is noteworthy that about 13, 30, and 76 percent of subjects achieved the level of independence (score 6 or 7) in individual functional tasks of motor domain (such as self-care and mobility activities), at the times of admission, discharge, and six-months poststroke, respectively. Also, in cognitive domain, about 61, 75, and 86 percent were considered independent at the times of admission, discharge, and six-month follow-up, respectively.The study showed that there was a direct linear correlation between each subject’s total FIM score and the scores of motor and cognition domains on all follow-up visits. It means that, obtaining a higher score on initial evaluation led to higher scores at the times of discharge and six months later. Also, more independence in motor domain accompanied better cognitive function.There was a significant inverse relation between subjects’ age and their FIM scores, at the times of discharge and six-month follow-up visit (P < 0.001). However, this association was not obtained between age and admission’s FIM score. We also observed that the gain in FIM score was inversely linked to the age and it was significantly lower after 60 years old (P = 0.010). We did not observe any association between gender and FIM scores. No significant correlation was observed between type of CVA and FIM scores .The study showed that longer duration of stay at hospital was associated with lower scores of total FIM, and also motor and cognition subscales, on discharge and six-month follow-up visits .The gain in subjects’ FIM scores was inversely correlated to the admission FIM score. So subjects with less initial FIM score, showed more remarkable improvement in latter stages. This relation was also observed in motor and cognition subscales  .14 In our study, subjects achieved this level of independence on six-month follow-up visits.We observed a significant improvement in total FIM score and also its motor and cognition subscales on follow-up visits. The mean (and range) of total FIM scores were 86 (15-119), 102 (16-123) and 119 (17-126) for admission, discharge and six-month poststroke, respectively. According to some studies, FIM score of more than 108 is roughly indicative of home independence.15, the least significant changes for total FIM, motor and cognition scores were 22, 17 and 3, respectively. Compared to their findings our patients showed these least significant changes. Our findings revealed a direct linear correlation between scores of total FIM and its motor and cognition subscales at all follow-up sessions. Considering this, higher FIM score on admission led to higher scores on discharge and six months afterward. These results conformed other studies’ findings.8,16-18Based on the study by Beninato et al.16 Another study by Tokunaga et al.19 showed that the gain in FIM score, in completely dependent or completely independent subjects is minimal. According to this, not much of improvement is expected in functional status of these patients.According to our study, gains in motor domain were significantly higher than cognition. This improvement was specifically observed in category of self-care. Assessment of results revealed a mean increase of 12 (range: 6-80) and 13 (range: 1-40) in total FIM scores at admission and discharge, respectively. Comparison of these findings showed no significant difference. The above statement applied to motor domain too. It was different in cognition domain. The results showed significantly higher improvement in subjects’ cognition domain of FIM score during the hospital admission. We observed fairly small changes in patients’ cognitive status at staying home periods. On the other hand, about 86% of subjects got the maximum score of cognition domain on six-month follow-up visits. Putting these findings together, it can imply the relative weakness of FIM score in detecting subtle changes of cognitive status. This conclusion is consistent with the results of Hall et al. study.17,20,21 Tur et al.20 found that in addition to age, the time gap between accident and admission to hospital and also initial FIM score are predictive of FIM score at discharge. In our study, the age and FIM score of preliminary visit along with duration of hospital residence significantly affected the FIM score at discharge but age did not have a significant effect on admission and the FIM score at discharge. The FIM score of six-month follow-up visit was significantly affected by age, but there was a rather weak correlation coefficient (-0.33). Tokunaga et al.19 showed in their study that as the age increased, the admission FIM score and its improvement significantly decrease.In our study, the overtime improvement in FIM score was inversely linked to subject’s age. The gain in total FIM score and motor domain were significantly lower in those aged over 60. Our findings match the observation of other trials. Studies confirm that older subjects gain lower FIM scores.22 higher age and lower FIM scores decrease the possibility of subject’s discharge to home. They also showed that the age and initial FIM were inversely correlated with FIM improvement. These observations are compatible with ours. In our patients, the FIM scores of discharge and six-month follow- ups were inversely correlated with the admission FIM score. This dependence was also observed in motor and cognition domains. Also, assessment of expired patients’ characteristics revealed that the age and initial FIM score were good predictors of death. In our study, patient’s gender and type of stroke did not affect the FIM scores at admission or follow-up visits. We could not find any study evaluating these two factors.One final objective of stroke rehabilitation is release of patients to home. According to the study by Koyama et al.,23,24 In a systematic review by Chumney and colleagues4 in 2010 for validation of FIM questionnaire in stroke patients, they observed that despite its limitations, the FIM score can accurately predict the stroke outcomes. Hamilton et al.25 evaluated interrater reliability of FIM score, and its motor and cognition domains and also, FIM item score agreement in 1081 patients. Intraclass correlation coefficients (ICC) for total FIM, motor and cognition domain were 0.96, 0.96, and 0.91, respectively. ICC for subscales score ranged from 0.89  to 0.94 (self-care). They concluded that the FIM, when used by trained rehabilitation clinicians, is reliable enough. In study by Kwon et al.,26 a high correlation was observed between motor component of FIM, Barthel index and Modified Ranking Scale. In another study by Dodds et al.,27 Uniform Data System (UDS) data on 11102 general rehabilitation inpatients were examined and they conclude that the FIM has high internal consistency. Also, Hall et al.28 reported a high correlation coefficient between FIM and disability rating scale.Our survey on the studies of FIM score showed that it has been used as a measurement device in rehabilitation of stroke, traumatic brain or spinal cord injury, and multiple sclerosis (MS), in elderly and youth populations.One shortcoming of FIM scale is that this tool evaluates subject’s independence in ADL performance, but not the way of its accomplishment. Many neurobehavioral disorders affect the quality of task performance, but not just the happening of it. In such a case, despite final task accomplishment, the occurrence of several errors place obstacles in the patient’s way to meet the purpose. Elimination of this defect needs applying more sophisticated and precise measurement tools.29 Also in a study by Smith et al.,30 it was shown that there is good intermodal agreement for telephone assessment using the FIM and in-person assessment. They also demonstrated that the main factor affecting the data collection was subject’s communication skills.30 Despite these, it was better using the version available for telephone interviews and this can be considered as a limitation of our study. The other potential source of bias in current study was relatively wide range of discharge visits. According to our findings, time had a positive effect on patients’ FIM scale. Although it was not as wide as some other studies,31 this difference in timing of follow-up visit might have affected the results.Finally, it is noteworthy that FIM score must be applied by a skilled practitioner. It is self-evident that lack of enough training might threat the measurement reliability. We accomplished the six months follow-up evaluation through a telephone call. There are some studies that used telephone interview for evaluation of subjects’ FIM scale.In current study, we designed the rehabilitative plans subjectively and based on patients’ individual needs and deficits. According to our knowledge, a predetermined standard CVA rehabilitation protocol has not been defined yet. Assessment of different rehabilitation plans and comparison of their effects needs to be accomplished in separate clinical trials with precise planning of different rehabilitation protocols. We suggest planning more clinical trials to evaluate the effect of different rehabilitation options.The study showed that the FIM is a valid tool for evaluation of stroke patients, their follow-up, and tracking the disease course. Also, we concluded that stroke patients make a significant improvement in their functional status overtime. The exact effect of rehabilitative procedures and comparison with no treatment must be assessed in separate studies.


Background. The relevance of speech-language-hearing therapy (ST) duration to language impairment remains unclear. Objective. To determine the effect of ST duration on improvement in language impairment as a stroke sequela and to compare the findings with those for occupational therapy (OT) and physical therapy (PT). Methods. Data regarding patients with stroke sequelae who were registered in the Japanese Association of Rehabilitation Medicine database were analyzed. Propensity scores for ST, OT, and PT duration were calculated using logistic regression, followed by inverse probability weighting in generalized estimating equations to examine the odds ratio for improvement in the Functional Independence Measures scores for comprehension, expression, and memory. Analyses stratified by age and dementia severity were also conducted. Results. Compared with short-duration ST, long-duration ST was significantly associated with improved scores for comprehension and expression in the overall study population and in some groups, with higher benefit especially for younger participants (<64 years) and those with more severe dementia. A significant but less pronounced effect was also observed for OT and PT. Conclusion. Long-duration ST is more effective than long-duration OT or PT for improving language impairment occurring as stroke sequela. However, these effects are limited by age and severity of dementia. A large number of studies on rehabilitation training for stroke sequelae have been performed worldwide –3. HowevIn some cases, occupational therapy (OT) for impaired upper limb function and physical therapy (PT) for impaired walking function and standing balance are prescribed simultaneously with ST for language impairment. Similar to ST, OT and PT typically involve one-on-one training with the patient. It is believed that the patient experiences a similar benefit from receiving training instructions verbally and participating in natural conversation during OT and PT to that from receiving instructions during ST, and these interactions likely influence the degree of improvement in language impairment. Thus, to determine the need for prescribing ST, it is important to know whether the effects of OT and PT are similar to those of ST in terms of mitigating language impairment after stroke. However, few studies have separately and simultaneously investigated the influences of ST, OT, and PT duration on language impairment –12.Human communication involves several processing steps from comprehension to expression of language. Sound originating from the speaker is first assessed in Wernicke's area (receptive language), and the information is then transferred by the arcuate fasciculus to Broca's area, where expressive language is generated. The information is subsequently sent from Broca's area to the motor cortex to be expressed as speech –16. It iThe present study evaluated the influence of ST duration on the degree of improvement in language impairment that occurs as a sequela of stroke. In addition, we investigated the influence of OT and PT duration on the degree of improvement in language impairment and compared the findings to those noted for ST. Moreover, we performed further analyses with patients stratified by age and severity of dementia.The Japan Association of Rehabilitation Database includes quality data collected, curated, and maintained as a foundation for advancing science. The database includes data of stroke patients and patients with femoral neck fracture or spinal cord injury, who were treated at a hospital and then transferred to a rehabilitation center for training. We used data registered from 33 hospitals between 2005 and 2013. We extracted the data regarding stroke patients and excluded deficient or incorrect data. The following data were extracted for each patient: demographic characteristics including age and sex; type of rehabilitation training ; rehabilitation training duration; and Functional Independence Measures (FIM) scores –20 for cOf the five items included in the FIM cognitive assessment instrument, we selected comprehension, expression, and memory as objective variables describing language impairment. To assess the effect of the therapy on language impairment, the FIM cognitive items related to language function  were assessed in terms of the change in score between admission and discharge, thus indicating whether the patient's condition had improved, worsened, or remained the same after rehabilitation training. These changes were expressed as binary variables, distinguishing between categories of patients defined based on the effect of the therapy.Binary variables were also used to represent the duration of ST, OT, and PT. In the current sample, the 25%, 50%, and 75% percentiles of treatment dose were 1.3, 22.3, and 53.7 hours for ST; 29.0, 56.0, and 90.0 hours for OT; and 28.0, 58.0, and 99.0 hours for PT, respectively. The 25%, 50%, and 75% percentiles of total treatment duration  per patient were 72.0, 141.7, and 239.0 hours, respectively. Based on integer value immediately following the median value, the durations of ST, OT, and PT were converted into binary variables indicative of treatment duration to serve as explanatory variables: <23 versus ≥23 hours, <56 versus ≥56 hours, and <58 versus ≥58 hours, respectively.Additionally, we used the following factors as covariates: age; sex; hospital; year of hospitalization; level of deficiency in activities of daily living, according to the standardized assessment manual for the elderly with dementia , 22 at hPatients were divided according to age into the following four groups: ≤54 years, 55–64 years, 65–74 years, and ≥75 years. Patients were divided according to hospitalization year into 2009 or earlier and 2010 or later. According to the dementia level, we divided the patients into the following four groups: normal, mild-to-moderate, severe, and unknown. Specifically, grades 1–2b (mild-to-moderate dementia) describe patients who show some form of dementia but are still largely independent in daily life, both at home and in a social setting, as well as patients who have some disabling symptoms, behaviors, or communication difficulty, even at home, but are still able to act independently as long as appropriate assistance is provided. Grades 3a–M (severe dementia) describe patients who sometimes exhibit disabling symptoms, behaviors, and communication difficulties and require assistance, as well as patients who exhibit significant psychiatric symptoms, behavioral problems, or serious physical disabilities and require specialized medical care.Patients were divided according to the Japan Coma Scale score as follows: normal, single-digit, double-digit, triple-digit, and unknown scores. Single-digit scores denote patients who are awake even without stimulation. Double-digit scores denote patients who can awaken when stimulated. Triple-digit scores denote patients who do not awake when stimulated (comatose).Patients were divided according to the FIM locomotion  score at hospitalization as follows: score of 1-2, 3–5, and 6-7 and unknown. Patients having a score of 1-2 cannot walk for more than 15 m, those having a score of 3–5 can walk with assistance, and those having a score of 6-7 can walk unassisted. The patients were also stratified according to FIM scores for comprehension, expression, and memory at hospitalization: score of 1-2, 3–5, and 6-7 and unknown.According to the length of hospitalization  expressed using binary variables, the patients were divided into two groups: ≤91 days and ≥92 days. Additionally, patients were divided according to the side with more severe paralysis as follows: 1, right side; 2, left side; and 1.5, unknown.We developed propensity scores  using a In order to develop the propensity scores, ST, OT, and PT data were analyzed using logistic regression analysis, and the response to long- versus short-duration training was included as an objective variable, while various covariates were included as explanatory variables. Subsequently, we used these propensity scores as explanatory variables to examine changes in comprehension, expression, and memory scores as objective variables and determined the odds ratios (ORs) with 95% confidence intervals (CIs) by inverse probability weighting using a generalized estimation equation. Robust estimation was performed in this assessment.To calculate the weighting variable, the inverse sampling probability of each individual in the sample was divided by the mean inverse sampling probability of all individuals. This yielded a weighting variable that was scaled such that the mean weight of all individuals would be 1, while the weighted sample size would be equal to the actual, unweighted sample size.We performed similar analyses after stratification according to age and dementia level in order to investigate the significance of the duration of rehabilitation in elderly patients and in patients with dementia complications. To confirm the validity of the assessment of dementia level, we analyzed its correlation with the MMSE  scores up value of <0.05 was considered statistically significant. The results of the analyses are expressed in terms of ORs, 95% CIs, and p values.All statistical analyses were performed using SPSS version 24.0 , and a The basic characteristics of the patients are presented in An overview of the influence of different ST, OT, and PT duration on the degree of improvement in FIM comprehension score is presented in An overview of the influence of different ST, OT, and PT duration on the degree of improvement in FIM expression scores is presented in An overview of the influence of different ST, OT, and PT duration on the degree of improvement in FIM memory scores is presented in p < 0.001), confirming that dementia level was strongly associated with the MMSE score. The mean MMSE values were 25.7  for patients with no deficit , 21.4  for patients with mild-to-moderate dementia, 14.8  for patients with severe dementia, and 20.7  for patients with unknown dementia level.To confirm the validity of the standardized assessment of dementia level, we analyzed the data from 426 patients who also underwent MMSE. Spearman's correlation coefficient between the results of the two instruments was −0.591 , with the greatest effect on comprehension. Additionally, OT and PT had a partial influence on language improvement, but the overall effect of OT and PT was less pronounced than that of ST.Bhogal et al.  comparedAmong younger patients, the influence of longer ST was greater than that noted in the older patients, who did not show significant differences between the effects of short- and long-duration treatment. Kelly-Hayes et al.  reportedIn the present study, we used the standardized assessment manual for elderly  to assesOverall, we found that, compared to OT or PT, ST improved aphasia to a greater extent. In this study, we used OT and PT as control variables. OT is usually prescribed to improve activities of daily living , 34, whiWe employed inverse probability weighting after creating propensity scores using logistic regression analysis. Another option for analysis is the use of propensity score matching. However, we did not employ this method because it is nearly impossible to match between identical trend scores. If there is an imbalance in the sample of each group, then large amounts of data from one of the groups might be lost. Estimation with regression analysis requires trend scores and objective variables to be in a linear relationship; however, there is no reason to assume that propensity scores themselves would have a linear distribution. Inverse probability weighting is a technique that was developed to overcome these issues. This technique offers the ability to determine each group's marginal standard error and to have higher precision adjustments than those achievable in propensity score matching. While the analyses were performed on the initial assumption that only patients likely to improve with long-duration rehabilitation training were included, the use of propensity scores followed by the use of inverse probability weighting clarifies such assumptions.The present investigation was a large-scale study using data regarding more than 3,500 patients treated in various hospitals and settings. Of the three previous studies that reported a beneficial effect of ST –39, one The present study had several limitations. First, we did not have access to data regarding certain relevant confounding factors including lesion location as well as prestroke educational history, occupational history, and language level. Therefore, it was impossible to adjust for these confounding factors. Second, language abilities were assessed using three items from the FIM instrument, and no formal, extensive language assessment was conducted. Finally, the specific modalities and delivery of the various ST, OT, and PT interventions were not controlled for. Further studies are needed to overcome these limitations.Compared to short-duration ST, long-duration ST may provide better improvement in language impairment as a sequela of stroke. OT and PT may provide additional benefit regarding the improvement in communication abilities, but their effectiveness is less pronounced than that of ST. With respect to specific groups of patients, younger patients (<64 years) and those with more severe dementia benefit the most from undergoing long-duration ST instead of short-duration ST. Therefore, when evaluating the therapeutic strategy for aphasia patients after stroke, longer duration of ST should be considered especially in these groups of patients.


There was no difference in the improvement of cardiomyopathy between the TMZ and control group. No publication bias was shown for PHR . There were significant differences in LVEF, LVESV, SWTSI, LVESD, and LVEDD between the TMZ group and the control group. TMZ-treatment significantly increased the level of LVEF : 5.46–7.84, P<0.001), and reduced the level of LVESV , SWTSI , LVESD , and LVEDD . There was no publication bias except for LVEDV . TMZ is effective for cardiomyopathy treatment and worth to popularize in clinic.To explore the effect of trimetazidine (TMZ) in cardiomyopathy treatment. Literatures, related with TMZ treatment for cardiomyopathy, were retrieved between 1990 and February 2018 in the Pubmed, Embase, and Cochrane Library systems. Cardiopulmonary exercise testing  and echocardiographic results  were merged to detect the publication bias. Total 898 patients with cardiomyopathy were divided into two groups: TMZ-treated group ( Cardiomyopathy, defined as myocardial disease associated with cardiac functional insufficiency, is divided into primary and secondary cardiomyopathies . The manAt present, trimetazidine was widely used in the treatment of cardiomyopathy, but there were no consistent reports on the efficacy of TMZ for cardiomyopathy treatment. Therefore, it is necessary to make a comprehensive evaluation of the efficacy of TMZ in the treatment of cardiomyopathy by means of meta-analysis, providing a basis for the clinical treatment of cardiomyopathy.http://www.ncbi.nlm.nih.gov/pubmed), Embase (http://www.embase.com), and Cochrane Library (http://www.cochranelibrary.com) with the following key words: ‘cardiomyopathies’ or ‘cardiomyopathy’ or ‘myocardiopathy’ in combination with ‘TMZ’ or ‘trimetazine’ or ‘vastarel’ or ‘vasorel’. The study type is a randomized controlled study, the study language is limited to english, and the last search was updated on February 2018.The comprehensive search was performed to retrieve the related clinical studies in Pubmed (Inclusion criteria for studies were shown as follows: (1) published literature on the clinical study of TMZ therapy in cardiomyopathy; (2) the study type is a randomized controlled study; (3) it could provide the comparison of the efficacy between TMZ and control groups in the treatment of cardiomyopathy; (4) mainly included some outcome indicators of cardiopulmonary exercise testing and echocardiographic.Exclusion criteria were as follows: (1) data were not complete or not available for statistical analysis; (2) non-original studies, such as reviews, letters etc.; (3) duplicate publication; (4) the data from the same population used for multiple studies are only included in the latest research or one of the most complete information, with the remainder excluded.Two authors (F.Q. and N.Z.Z.) independently extracted the following information of studies: first authors, publication year, research area, follow-up time, the patients number of the TMZ and control group, age and gender of patients, and left ventricular ejection fraction (LVEF) indexes before treatment and outcome related (cardiopulmonary exercise testing and echocardiographic).Quality assessment was processed using the evaluation instrument recommendated by Cochrane Collaboration for bias risk assessment.If there are differences of opinion, discrepancy between the two investigators, the third investigator was invited to discuss for consensus.Q test based on Chi square [2I statistic. If the heterogeneity test was statistically significant (P<0.05 or 2I > 50%), the random effect model (REM) was used to calculate the combined effect value; otherwise, fixed effect model (FEM) was used to merge data (P<0.05 and 2I > 50%) [All procedures of meta-analysis were performed using R 3.12 software . The quantitative data effect index is represented by mean difference (MD) and its 95% confidence interval (CI). The heterogeneity test, which used to check whether the results of individual studies are unifiable, was analyzed by i square  and I2 s2 > 50%) . Egger’sThe search results and selection process of literature were shown in n=456) and control group (n=442). Selected articles published between 1990 and 2016, and most published after 2001 (13/14). The study area is mainly in France, Italy, Denmark, Egypt, and China, the follow-up time was usually 3–6 months, the patients in included studies were mainly male with middle-aged or elderly. General conditions of these patients, including gender, age, and LVEF before treatment were not statistically different between two groups. The relevant outcome measures (cardiopulmonary exercise testing and echocardiographic) were recorded in The general features of the selected literature were shown in P-value of the Q test and the 2I statistic.First of all, the heterogeneity test was carried out. Then the proper effect model was used to calculate the combined effect value according to the P<0.05 and 2I > 50%), fixed utility models were used for merging. The results showed that PHR , PSBP , RHR , and RSBP . There was no difference in the improvement of cardiomyopathy between the TMZ and control group. After assessing by the ‘Egger’s’ method, no publication bias was shown for PHR   .P<0.05 and 2I > 50%), and random utility model was used for merging. The results showed that LVEF , LVESV , LVEDV , SWTSI , LVESD  and LVEDD . There were significant differences in LVEF, LVESV, SWTSI, LVESD, and LVEDD between the TMZ group and the control group. TMZ-treatment significantly increased level of LVEF, and reduced level of LVESV, SWTSI, LVESD, and LVEDD. Publication bias was assessed using the ‘Egger’s’ method. The results showed that there were no publication bias except for LVEDV    and 5.We performed a meta-analysis for TMZ effect on cardiomyopathy treatment, found that TMZ had effects on the treatment of ischemic cardiomyopathy and dilated cardiomyopathy, and improved clinical symptoms. TMZ initially used as an anti-ischaemic or ‘cytoprotective’ agent through regulating a metabolic pathway of switching cardiac metabolism from FFA to glucose oxidation, increasing glucose utilization, improving the rate of ATP production, optimizing energy, thereby reducing myocardial damage, and achieving purpose of myocardial protection . FFA inhAt present, there are many researches on TMZ-treatment for cardiomyopathy. Some studies had shown that TMZ-treatment could improve left ventricular(LV) function and exercise tolerance, and reduce plasma levels of type-B natriuretic peptide, and cardiac troponin T levels in patients with ischemic cardiomyopathy , 25. In Improving cardiac function of patients with cardiomyopathy is the most important treatment target . In the In order to test the reliability of previous studies, the present study conducted a meta-analysis of TMZ for cardiomyopathy treatment to ensure the reliability of these conclusions. It has to be mentioned that there are some limitations in the present study. First, due to some incomplete data, no covariates were corrected, and no subgroup analysis was also performed. These potential confounding factors might affect the results of meta-analysis. Second, publication bias exists in LVEDD, which might have an impact on the synthetic results. Third, the included articles with four indicators of cardiopulmonary exercise testing results were too fewer; thereby, publication bias assessments could not be processed.In conclusion, this meta-analysis showed that TMZ is effective for cardiomyopathy treatment, and a growing body of evidence supports that the potential role of TMZ in treating patients with heart failure. However, this conclusion still needs to be validated by larger-scale, higher-quality studies, or updated meta-analysis with more samples.


The association between fibroblast growth factor receptor 2 (FGFR2) polymorphism and breast cancer (BC) susceptibility remains inconclusive. The purpose of this systematic review was to evaluate the relationship between FGFR2  polymorphism and BC risk. PubMed, Web of science and the Cochrane Library databases were searched before October 11, 2015 to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Sensitivity and subgroup analyses were conducted. Thirty-five studies published from 2007 to 2015 were included in this meta-analysis. The pooled results showed that there was significant association between all the 3 variants and BC risk in any genetic model. Subgroup analysis was performed on rs2981582 and rs2420946 by ethnicity and Source of controls, the effects remained in Asians, Caucasians, population-based and hospital-based groups. We did not carryout subgroup analysis on rs2981578 for the variant included only 3 articles. This meta-analysis of case-control studies provides strong evidence that FGFR2  polymorphisms were significantly associated with the BC risk. For rs2981582 and rs2420946, the association remained significant in Asians, Caucasians, general populations and hospital populations. However, further large scale multicenter epidemiological studies are warranted to confirm this finding and the molecular mechanism for the association need to be elucidated further. Breast cancer (BC), one of the most common malignant tumors among women worldwide, has the highest mortality rate in female cancer. Its incidence rate is increasing year by year and the patients are becoming younger and younger in the world , 2. BC iIn recent years, genome-wide association study (GWAS) provides a good technical support for the study on the susceptibility loci with high variation frequency and low penetrance . Large nLots of researches have reported the association between FGFR2  polymorphism and BC risk. However, due to differences in ethnic and regional and other factors, the conclusions of related reports are still inconclusive. Raskin et al  found thThe specific search process is shown in Figure The FGFR2  polymorphisms genotype distribution and allele frequencies incase groups and control groups were shown in Table For rs2420946, 11 studies with 7,840 cases and 9,349 controls were included to assess the association. As shown in Table 3 papers with 833 cases and 1012 controls were adopted to evaluate the association between the rs2981578 polymorphism and the BC risk. As shown in Table As shown in Table Q statistic. Random-effect models were applied if p-value of heterogeneity tests were less than 0.1 (p ≤ 0.1), otherwise, fixed-effect models were selected  polymorphism and BC risk. However, due to differences in ethnic and regional and other factors, the conclusions of related reports are still inconclusive. Thus, we conducted the meta-analysis to evaluate the relationship between FGFR2  polymorphism and BC risk.In our study, there were 31 studies with 54,677 cases and 80,418 controls for FGFR2 rs2981582 variants. In the total population, the pooled results indicated that the correlation between FGFR2 rs2981582 polymorphism and the occurrence of BC was significant in any genetic model. Furthermore, in ethnicity-specific analysis, FGFR2 rs2981582 were also significantly associated with BC risk both in Asians and Caucasians. We didn't discuss the African subgroup for just one study was from African. The analysis in different source of controls showed the same association between FGFR2 rs2981582 polymorphism and BC susceptibility both in HB and PB, indicating that both hospital populations and general populations followed the same relationship. For rs2420946, 11 studies with 7,840 cases and 9,349 controls were included to assess the association. In the total population, the pooled ORs suggested that rs2420946 was significantly associated with BC susceptibility in all the five genetic models. When stratified by ethnicity and source of controls, the results showed the same association in Asians, Caucasians, hospital populations and general populations, indicating that different genetic backgrounds and living environment were not strong enough to change these associations. All the results for the two variants  were partially consistent with the consequences of Wang's , Peng's Three articles with 833 cases and 1012 controls were adopted to evaluate the association between the rs2981578 polymorphism and the BC risk. As the preceding two variants, the association between rs2981578 variant and BC susceptibility was also significant in any genetic model. For just only 3 studies, no stratified study was conducted for rs2981578 polymorphism. However, in Zhou's  meta-anaOur meta-analysis has several limitations. First, our study is a summary of the data. For lack of all individual raw data, we could not assess the cancer risk stratified by other covariates including age, sex, environment, hormone level, menopause age and other risk factors. We also cannot analyze the potential interaction of gene-environment and gene-gene. Second, only published papers were included in our meta-analysis, there still may be some unpublished studies which are in line with the conditions. Therefore, publication bias may exist even no statistical evidence was found in the meta-analysis. Third, for just only 3 papers, no stratified study was conducted for rs2981578 polymorphism. Moreover, our study is a summary of the data. We did not verify it from the level of molecular mechanism. Data from large scale multicenter epidemiological studies is still needed to confirm the relationship between FGFR2  polymorphisms and BC risk, and the molecular mechanism for the associations need to be elucidated further.In conclusion, our meta-analysis based on case-control studies provides strong evidence that FGFR2  polymorphisms are significantly associated with the BC risk. For rs2981582 and rs2420946, the association remained significant in Asians, Caucasians, general populations and hospital populations. However, further large scale multicenter epidemiological studies are warranted to confirm this finding and the molecular mechanism for the associations need to be elucidated further.We searched PubMed, Web of science and the Cochrane Library for relevant studies published before October 11, 2015. The following keywords were used: (Fibroblast Growth Factor Receptor 2 or FGFR2) and (variant* or genotype or polymorphism or SNP) and (breast) and (cancer or carcinom* or neoplasm* or tumor), and the combined phrases for all genetic studies on the association between the FGFR2  polymorphism and BC risk. The reference lists of all articles were also manually screened for potential studies. Abstracts and citations were screened by two researchers independently. All the eligible articles need a second screening for the full-text. The searching was done without language limitations.i)independent case-control studies for humans; ii) the study evaluating the association between FGFR2  polymorphism and BC risk; iii) the study presenting available genotype frequencies in cancer cases and control subjects for risk estimated; iiii) cases should have been diagnosed by a pathological examination. We excluded comments, editorials, systematic reviews and studies lacking sufficient data or studies with male cases. If the researches were duplicated or shared in more than one study, the most recent publications were included.Inclusion criteria: A study was included in this meta-analysis if it met the following criteria: We used endnote bibliographic software to construct an electronic library of citations identified in the literature search. All the PubMed, Web of science and the Cochrane Library searches were performed using Endnote. Duplicates were found automatically by endnote and deleted manually. All data extraction were checked and calculated twice according to the inclusion criteria listed above by two independent investigators. Data extracted from the included studies were as follows: First author, year of publication, country, Ethnicity, Source of controls, Genotyping method, number of cases and controls and evidence of Hardy-Weinberg equilibrium(HWE) in controls. A third reviewer would participate if some disagreements were emerged, and a final decision was made by the majority of the votes.2χ test in the control group of each study [Z test was used to assess the significance of the ORs, 2I and Q statistics was used to determine the statistical heterogeneity among studies. A random-effect model was used if p value of heterogeneity tests was no more than 0.1 (p ≤ 0.1), and otherwise, a fixed-effect model was selected [p< 0.05 was considered statistically significant. We performed subgroup according to Ethnicity and Source of controls.All statistical analyses were performed using STATA version 11.0 software  and Review Manage version 5.2.0 . Hardy-Weinberg equilibrium (HWE) was assessed by ch study . The strselected , 22. Senselected , 24. The


Clostridium difficile infection (CDI) in surgical patients, its frequency per surgical wards and in-hospital-mortality at a single hospital.The objective of this study was to investigate independent risk factors (RFs) connected with healthcare-associated (HA) Risk factors for the infection were prospectively assessed among surgical patients with laboratory confirmed HA CDI and compared with a control group without HA CDI.P = 0.007, OR: 10.62, 95% CI: 1.93–58.4), the admission to intensive care unit , and the administration of 3rd generation cephalosporins . Patients with HA CDI had significantly higher in–hospital mortality compared to controls .The overall incidence rate of HA CDI was 2.6 per 10000 patient-days. Significant independent RFs for HA CDI were the use of carbapenems (CDI is an important HA infection in population of surgical patients and this study emphasizes the importance of the wise use of antibiotics, and other infection control strategies in order to prevent HA CDI, and to decrease the incidence and in-hospital mortality rate. Clostridium difficile (C.difficile) infections (CDI) has changed rapidly, with increases noted in the incidence of diseases internationally, and in the reports of CDI outbreaks within healthcare institutions in the USA, Canada and Europe. The increase of CDI incidence was partly associated with the epidemic emergence of a new C. difficile ribotype 027, which was also described to cause more severe infections [During the current century the epidemiology of fections . CDI becfections . The repfections –11. Patifections –10, 12. fections , 11. TheThe aim of this study was to investigate independent RFs associated with HA CDI in surgical patients, its frequency per surgical wards and in-hospital-mortality in a tertiary healthcare centre in Serbia.The Military Medical Academy (MMA), Belgrade, Serbia, a teaching hospital of the University of Defense, is a 1200-bed tertiary healthcare centre divided into 27 departments. The department of Infection Control performs continuous surveillance of the MMA patients. The surveillance of HA infections, including CDI, covered patients in surgical clinics of the MMA: Urology, General Surgery, Orthopedics/Traumatology, Neurosurgery, Maxillofacial Surgery, Plastic Surgery/Burns, Vascular Surgery, Thoracic Surgery, Cardio Surgery, Otorhinolaryngology, and Ophthalmology.Diabetes mellitus, malignancy, and factors related to healthcare including previous hospitalization in other hospitals, intensive care unit (ICU) admission, duration of treatment in ICU, mechanical ventilation, nasogastric tubes, previous use of corticosteroids, histamine-2-receptor antagonists (H2RAs), proton-pump inhibitors (PPIs) and antibiotics . Also, data about in-hospital mortality were recorded.Through regular hospital surveillance of surgical patients we prospectively identified all patients who had new HA, laboratory confirmed postoperative CDI during the study period, from 1st January 2011 to 31st December 2012. Reviewing the clinical chart information on patient characteristics, RFs related to healthcare were collected. We gathered data on the following variables: intrinsic factors (existing at admission) sex, age, C. difficile toxins A and B in a stool sample, which was derived more than three days after admission. Control patients were matched to the cases according to the inpatient ward, gender, age (±5 years), and date of surgical operation.In the case–control study, every surgical patient with HA CDI was compared with two control patients without CDI. HA CDI was defined as diarrhea (≥3 daily) which was acquired more than three days after admission to the surgical department and detection of C. difficile toxins A and B were used (BIOMERIEUX-VIDAS Clostridium difficile toxins A&B CDAB). Only patients who had never been diagnosed with CDI at the MMA were included in the control group, and only those who had not been diagnosed with CDI before enrolling in the study, were included in the case group, respectively. The Research Ethics Board of the MMA approved the research protocol. All study participants provided the informed written consent.Microbiological testing was performed at the Institute of Medical Microbiology at the MMA. Enzyme immunoassay kits for C. difficile toxin tests performed per 10000 patient-days. The in-hospital mortality rate was defined as the number of deaths per 100 patients. Data analyses were performed with SPSS, version 21.0 . Results were expressed as the mean ± SD or as the proportion of the total number of patients. The χ2 test or Fischer exact test were used for categorical variables and relative risk, and their corresponding 95% confidence intervals (CI) were calculated. For parametric continuous variables, mean values were compared using the Student t test. For nonparametric continuous variables the Mann–Whitney U test was used. RF independently associated with CDI were identified by stepwise logistic regression analysis of variables selected by univariate analysis, with a limit for enetering and removing variables from the model at 0.05.Incidence rate (IR) was defined as the number of HA CDIs per 10000 patient-days and per 1000 patients treated. The rate of testing (TR) was defined as the number of During 2011–2012 in the MMA 29033 surgical patients were treated during 255431 patient-days. A total of 67 surgical patients with CDI were registered  , the 3rd generation of cephalosporins  and admission to the ICU . According to the ULRA, PPIs usage was a significant RF for HA CDI (P = 0.05), but it was not a significant independent RF according to MLRA .Demographic and clinical characteristics of patients in the case and control groups according to ULRA are shown in Table vs 1.5%, P: 0.007; OR: 8.95; 95% CI: 1.84–43.43). Of 8 deaths in the case group, 6 or 75% were in the older than 65.In hospital-mortality was significantly higher by 9-fold in HA CDI compared to control , but lower than mean IR of 7.0 of HA CDI (country range 0.7–28.7) in a European, multicentre, prospective, biannual point-prevalence study of CDI in hospitalized patients with diarrhea (EUCLID) (4). In our hospital we have the practice of routine testing of all submitted diarrheal inpatient samples, but our TR in surgical patients in the two-year period was far lower than mean TR in European hospitals  (4).An association between female gender and CDI has been reported by previous population-based studies from the USA . SimilarC. difficile to colonize and overgrow within the gastrointestinal tract. Nearly all antibiotics have been implicated in CDI, but certain classes seem to cause higher risk for CDI. Stojanović confirmed in his study that all the groups of antibiotics, except for tetracycline, and trimetoprim- sulfamethoxazole, were statistically significant RFs for CDI [C. difficile [Among the main findings of this study are the identification of significant independent RFs for CDI in surgical patients, including carbapenems, admission to ICU and the 3rd generation of cephalosporins. The disruption of the normal flora caused by antibiotics allows ifficile . A recenifficile . The majifficile . Also, tifficile .The admission to ICU was significantly associated with CDI in our patients as reported before , 9. CritHowever, in a meta-analysis, Kwok et al. demonstrated the possible association between the PPI use and the incident and recurrent CDI. This risk was further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful . In our vs 5.3%) [The mortality rate in patients with CDI in this study was 12.1% and significantly higher than in the control group. Also, it is higher than it was reported in Veterans Health Administration (12.1% vs 5.3%) . This diOf 8 deaths in the case group, 6 or 75% were in the older than 65. CDI was not the primary cause of death but it was mentioned in the clinical chart information. A systematic review of unfavorable outcomes of CDI (68 studies), based on publications from 1978 until 2013, showed that mortality was associated with age, co-morbidities, hypo-albuminemia, leucocytosis, acute renal failure, and infection with ribotype 027 .C. difficile isolates received for typing from six hospital settings from South Europe (the MMA was not included) in time period from 2008 to 2015 and showed that PCR ribotype 027 and related ribotype 176 were detected in outbreaks in Croatia, Bosnia and Herzegovina and Serbia [Last data from a European, multicentre, prospective, biannual point-prevalence study of CDI showed that overall prevalence of ribotype 027 has risen more than three-fold (from 5% to 18%) and high endemicity of ribotype 027 has shifted from the UK and Ireland in 2008, to Germany and Eastern Europe in 2012–13 , 7. The d Serbia . Some PCC. difficile and detection of toxigenic isolates). This procedure has shown poor sensitivity of less than 50% in studies of Shin [C. difficile toxins can degrade at room temperature and the quality of CDI diagnostic also depends on transport time of the samples in the respective settings of the MMA. Both, the low rate of test performance in general and limitations of diagnostic test system, which we used, make it very likely that the actual incidence of CDI in our study was markedly higher.Important limitation of this study is that CDI testing was based on toxin A/B enzyme immunoassay (EIA) as the only diagnostic procedure in laboratory (no EIA detecting glutamate dehydrogenase, no nucleic acid amplification tests, no isolation of  of Shin  and Swin of Shin . The met of Shin . C. diffAnother limitation is the possibility of confounding variables that were not examined in our study. Although confounding variables were chosen after an exhaustive search of the literature, the potential for oversight and exclusion does exist. We tried to find all of the data in order to gain an understanding of the RF; we did not include some parameters, namely the diagnosis upon admission, all comorbidities, durations of the hospital stays, PPIs exposure in previous 30 days, the duration of PPIs and H2RA use, and outpatient antibiotic use, and analyzing these factors could have enhanced the relevance of our results. Furthermore, we did not evaluate the CDI cases and the controls in relation to the sex, age and wards in which they had undergone treatment, because CDI cases and controls were matched according to them.Another limitation is that we performed case–control study and that we have small sample size.The strengths of our study include its setting in a teaching hospital, and its 2-year duration. ULRA and MLRA strengthened the evidence.The results of the present study are valuable in documenting the relations between RFs and CDI in patients undergoing surgery and contribute to improve quality of health care. CDI is an important HA infection in population of surgical patients and this study emphasizes the importance of the wise use of antibiotics, and other infection control strategies to prevent HA CDI, decrease incidence and in- hospital mortality rate.


Comparison of these two types of learning in speed (response time) and accuracy (number of errors) showed the number of errors (P = 0.012) and response time (P = 0.012) in the implicit motor learning group of MS patients and the number of errors (P = 0.096) and response time (P = 0.954) in the explicit motor learning group of MS patients. Moreover, comparison showed the number of errors (P = 0.008) and response time (P = 0.05) in the implicit group of normal peers and the number of errors (P = 0.011) and response time (P = 0.442) in the explicit group of normal peers. The results showed that explaining and describing the task is less effective at training the motor sequence of MS patients and that these patients benefit more from implicit learning.This study tends to assess implicit and explicit types of motor learning in patients with Multiple Sclerosis (MS) and normal peers by means of a serial reaction time. Sample size was 15 for each group and Samples included 30 patients with MS and 30 normal peers and were assigned to implicit and explicit learning groups. A repeated measures ANOVA was used for measuring reaction time and response error, and a paired samples  Multiple sclerosis (MS) is a chronic, progressive, disabling disorder characterized by immune-mediated demyelination, inflammation, and neurodegenerative tissue damage in the central nervous system (CNS), associated with frequent exacerbations and remissions of neurologic symptoms and eventual permanent neurologic disability. The vast majority of patients suffer from recurrent relapses followed by remissions of neurological symptoms, especially in the early course of disease . People This quasi-experimental study was based on convenient sampling. By measuring the standard deviation of previous studies , the samAverage functional disability was calculated based on the extent of disability status scale (EDSS). The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. The scale was developed by a neurologist called John Kurtzke in 1983 as an advance from his previous 10 step Disability Status Scale (DSS). The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist . In asseMoreover, participants were compared to 30 controls in terms of age, gender, Wechsler Intelligence Scale, and the MMSE test, and no significant difference was found among these groups. Using parallel group pilot study plan, 15 patients and 15 controls practiced implicit learning, and 15 patients and 15 controls practiced explicit learning. Inclusion criteria included RRMS diagnosed by a neurologist, minimum literacy (able to read and write), and right hand dominance. Exclusion criteria included severe memory impairment (score less than 21 on MMSE test), acute disease, and neurological diseases such as dementia or Alzheimer’s disease, cerebellar problems, and severe depression, and severe visual and hearing problems. None of the patients experienced motor problems during SRT exercises. All patients and control groups stated their consent to participate in the study by signing a consent form.This examination was designed by Folstein (1975) . This teP = 0.06).This scale is a set of memory tests for adults that was designed and standardized by Wechsler in 1945. The Wechsler Intelligence Scale has two forms, A and B, each including 7 sections and different themes . This scale was standardized by Sarrami (1993) in Iran with Cronbach’s alpha coefficient of 0.85 . In the The Persian version of the SRTT application was used in this study. Studies showed that this test is not dependent on culture in terms of reliability and validity. Moreover, data is recorded by a computer; thus, human error is not involved in recording . StimuliAt this stage, the test involved 7 blocks. Block 3, 2, and 6 had a random arrangement and Blocks 5, 7, and 1 had a regular pattern. Here, they were not given any explanation of how the squares were repeating and were asked only that they see every square in the shortest possible time and press the corresponding key. Between every two sequential blocks, a1 min rest was given, and at the end, assign on the computer screen appeared indicating the end of the experiment. In the end, people were asked whether there was a repetitive pattern of squares or not. If there was a repetitive pattern, the people were asked to express it. If people, Correctly Expressed it, they were excluded from the implicit group and were included in the explicit group. Process in explicit group was similar to implicit motor learning group with the exception that pattern repeat squares and sequence and blocks was explained to the people. That is, in the first block, the sequence of appearance of colors were painted on the side, and then was removed.t-test and a repeated measures ANOVA were used to analyze data obtained from SPSS in the four groups. The results are presented below.A paired samples P = 0.094), and the paired t-test was not significant in irregular sequences (P = 0.838), which suggests that MS patients have similar errors in the explicit learning of irregular sequences.Based on the results obtained from the repeated measures ANOVA in explicit learning MS patients, there was no significant difference among the number of errors in regular steps (P = 0.954). Moreover, the paired t-test was not significant for the response time of irregular sequences (P = 0.216).There was no significant difference in response times of regular steps in explicit sequences for MS patients (P = 0.012); moreover, comparison of irregular steps by using the paired t-test showed no significant difference.Based on results obtained from the repeated measures ANOVA, there was a significant difference among the number of errors in regular steps (P = 0.012). Moreover, the paired t-test was not significant for response time of irregular sequences (P = 0.147).There was a significant difference in response times of regular steps in implicit sequence for this group (P = 0.006), while the main effect of the learning type showed no significant difference in accuracy (P = 0.844). Moreover, the main effect of the blocks showed a significant difference in learning speed (P = 0.009), while the main effect of the learning type showed no significant difference in speed (P = 0.431). A comparison of irregular steps (Blocks 2 and 6) showed no significant difference in accuracy (P = 0.512) and speed (P = 0.094) (The main effect of the blocks showed a significant difference in learning accuracy (= 0.094) .Implicit sequence learning involves learning a sequence of events, regardless of learning or awareness of what has been learned. This type of learning leads to many events and behaviors, including learning of new languages, understanding and production of complex sentences, walking with mobility aids, as well as various types of rehabilitation. In contrast, explicit learning includes conscious information of experiences. This study aimed at assessing the difference between implicit motor learning and explicit motor learning in patients with multiple sclerosis. Findings showed that implicit motor learning occurred in patients with MS, and there was no significant difference with normal peers. Motor performance of this group did not improve in regular blocks by exercise and showed a significant difference with the normal peer group. Explicit learning did not occur in the MS group, which probably indicates impaired learning in this group of patients. However, this type of learning occurred in healthy controls. Although no significant difference was found between the two groups, this learning was probably impaired. Motor performance of this group did not improve in irregular blocks by exercise and showed a significant difference with normal peers. Brain regions involved in learning sequential movements include cortex pre-motor, dorsal prefrontal cortex, and anterior supplementary motor area . Nervous


Over the past decades, reorganizations and structural changes in Swedish primary care have affected time utilization among health care professionals. Consequently, increases in administrative tasks have substantially reduced the time available for face-to-face consultations. This study examined how work-time was utilized and the association between work time utilization and the perceived psychosocial work environment in Swedish primary care settings.n = 441), including registered nurses, primary care physicians, care administrators, nurse assistants, and allied professionals. Response rates were 75% and 79% for the questionnaires and the time study, respectively.This descriptive, multicentre, cross-sectional study was performed in 2014–2015. Data collection began with questionnaire. In the first section, respondents were asked to estimate how their workload was distributed between patients (direct and indirect patient work) and other work tasks. The questionnaire also comprised the Copenhagen Psychosocial Questionnaire, which assessed the psychosocial work environment. Next a time study was conducted where the participants reported their work-time based on three main categories: direct patient-related work, indirect patient-related work, and other work tasks. Each main category had a number of subcategories. The participants recorded the time spent (minutes) on each work task per hour, every day, for two separate weeks. Eleven primary care centres located in southeast Sweden participated. All professionals were asked to participate  contains supplementary material, which is available to authorized users. Over the past few decades, reorganizations and structural changes in the Swedish health care system have affected how health care professionals utilize their time. One example is the implementation of electronic information technology, such as electronic patient records. When combined with a reduced number of health care administrators, this change has led to more administrative work tasks for health care professionals . ConsequIn a Swedish Health Policy survey, most PCPs were dissatisfied with the amount of time they could devote to patients, and they rated their job as very or extremely stressful . ComplexSeveral studies have shown that the skills and competences of health care professionals in primary care have been underutilized , 8. For To our knowledge, there is a shortage of studies on time utilization and on the psychosocial work environment in primary care, particularly studies that include all staff categories. From a managerial perspective, it is important to know how much time staff members spend on different work tasks; this information can be used to optimize clinical efficiency, ensure work satisfaction, and facilitate staff retention.The aims of this study were to investigate work-time utilization among different professionals in Swedish primary care and to explore associations between work-time utilization and the psychosocial work environment.A descriptive, multicentre, cross-sectional study was performed in primary care institutions in southeast Sweden.Sweden has nearly 10 million inhabitants. The increasing proportion of older individuals in the population presents a major challenge for the health care system, as in other northern European countries . In Swedn = 5) and urban (n = 6) areas and varied in size; the smallest had 20 employees and the largest had 81 employees. All professionals  were invited to participate, including RNs, PCPs, care administrators, nurse assistants (NAs), and allied professionals . The PCP group consisted of general practitioners and physicians in training. The employees at each primary care centre were informed about the study at a staff meeting. They also received written information.This multicentre study included four county councils , which served approximately 1.3 million inhabitants in southeast Sweden. Among the 151 primary care centres in this geographic area, this study selected 23 primary care centres, based on purposive sampling . The goaA questionnaire was distributed to all staff members at each primary care centre by e-mail with the web-based tool, Publech Survey 5.7. One reminder was sent after 2 weeks. In the first section of the questionnaire, participants were asked to estimate the proportions of time spent on work tasks that involved patients (directly and indirectly) and time spent on other work. Examples of work tasks were given for each of these categories . Also, participants assessed the psychosocial work environment with the validated instrument, the Copenhagen Psychosocial Questionnaire (COPSOQ) –16. The direct patient-related work tasks, and it included face-to-face contacts with patients and telephone contacts with patients or their next of kin. The second main category was indirect patient-related work tasks, and it included documentation of patient data, signing journal entries, prescribing medical drugs, and entering data into different health care records databases and quality registries. The third main category was other work tasks, and it included meetings with colleagues, continuing education, e-mail management, managing equipment and facilities, dealing with computer problems, waiting time, other writing/administrative tasks, and pauses . Prior to the main study, the form was validated by two experts (a PCP and a RN), and minor adjustments were made. The participants were given a pamphlet with instructions on how to complete the form. A total of 202 office hours were excluded from the analyses, due to incorrect reporting or illegibility; these were classified as internal drop-outs.Next, a time study was conducted with a form  that was developed specifically for this study . An item with five response alternatives was scored from 0 to 100, i.e. 0, 25, 50, 75, and 100 and a four-response item was scored 0, 33.3, 66.7, and 100. The standardized scores facilitated comparisons between different scales. The total score for a scale was calculated as the mean of the scores for the individual items in that scale. A difference of 5 in the mean value was defined as a clinically significant change for each scale . A high r correlation was used to analyse associations between COPSOQ scales and the proportions of time spent on different work tasks and associations between COPSOQ scales and age. A two tailed p-value ≤0.05 was considered statistically significant. Statistical analyses were performed with the Statistics Package for Social Sciences (SPSS) version 22.Response rates for study participation are expressed as the proportion of responses for each section of data collection. The responses were also subcategorized by profession and age. Age is expressed as the mean, range (min-max), and standard deviation (SD), for each profession and for the entire study sample. The mean estimated proportions of time spent on work tasks were compared to self-reported time use (based on the time study) with the paired t-test. Descriptive statistics of work tasks are reported as the mean percentage and the min-max. The means and SD of COPSOQ scales were compared between professions with the analysis of variance (ANOVA) and post-hoc Tukey test. Pearson’s Data collection was carried out from March 2014 to February 2015.This study was approved by the Ethics Review Board in Linköping, Sweden (D.nr. 2014/81–31). All data material was stored in a database with a high level of security that could only be accessed by the authors. Participants received information about the study verbally at a staff meeting and also by written information at the start of the data collection. Participants were informed that the study was voluntary, that they could drop out of the study without explanation at any time, and that confidentiality was guaranteed. Participants agreed to participate by responding to the questionnaire and time study.Overall, of 441 individuals invited to participate, 391 took part in the study; thus, the response rate was 89%. However, the response rates were different for the different types of data collection instruments  ensured that the risk of recall bias was minimized . The stuThis study indicated that Swedish primary care staff spent a limited proportion of their work time directly with patients. PCPs seemed to perceive their work environment in negative terms to a greater extent than other staff members. Allocation of time spent on work tasks influenced staff perceptions of the psychosocial work environment. Future research, possibly with a qualitative design, might shed further light on the results from this study and provide suggestions on how to improve the psychosocial work environment in primary care.The results of this study were not surprising, given the complex, bureaucratic organization in Swedish primary care. For more efficient use of work-time among medical staff in primary care, we recommend an increase in the number of administrative and service personnel.Additional file 1:Time study data collection form. The file contains the form where the participants recorded the time (min) they spent on each work task, every hour, every day, over two separate weeks, Monday to Friday, during office hours. The form contained three main categories  and a number of subcategories for each main category. (DOCX 26 kb)Additional file 2:Comparisons between professionals in COPSOQ scores. The means and SD of COPSOQ scales were compared between professions with the analysis of variance (ANOVA) and post-hoc Tukey test. (DOCX 18 kb)


Motor imagery (MI) is defined as mental execution without any actual movement. While healthy adults usually show temporal equivalence, i.e., isochrony, between the mental simulation of an action and its actual performance, neurological disorders are associated with anisochrony. Unlike in patients with stroke and Parkinson disease, only a few studies have investigated differences of MI ability in multiple sclerosis (MS). However, the relationship among disease severity, anisochrony and brain activation patterns during MI has not been investigated yet. Here, we propose to investigate MI in MS patients using fMRI during a behavioral task executed with dominant/non-dominant hand and to evaluate whether anisochrony is associated with disease severity. Thirty-seven right-handed MS patients, 17 with clinically isolated syndrome (CIS) suggestive of MS and 20 with relapsing-remitting MS (RR-MS) and 20 right-handed healthy controls (HC) underwent fMRI during a motor task consisting in the actual or imaged movement of squeezing a foam ball with the dominant and non-dominant hand. The same tasks were performed outside the MRI room to record the number of actual and imagined ball squeezes, and calculate an Index of performance (IP) based on the ratio between actual and imagined movements. IP showed that a progressive loss of ability in simulating actions  more pronounced for non-dominant hand, was found as function of the disease course. Moreover, anisochrony was associated with activation of occipito-parieto-frontal areas that were more extensive at the early stages of the disease, probably in order to counteract the changes due to MS. However, the neural engagement of compensatory brain areas becomes more difficult with more challenging tasks, i.e., dominant vs. non-dominant hand, with a consequent deficit in behavioral performance. These results show a strict association between MI performance and disease severity, suggesting that, at early stages of the disease, anisochrony in MI could be considered as surrogate behavioral marker of MS severity. Motor imagery (MI) is defined as a dynamic state during which the representation of a specific motor action is internally reactivated within working memory without any actual motor output  and showed that patients had a significantly lower accuracy score than controls in correctly executing a hand rotation task  to investigate the neural correlates of MI in patients with MS using fMRI during a task executed with the right and left hands; (b) to explore the association among disease severity, anisochrony and brain activation patterns during MI. In particular, we focused our attention on the first stages of the disease, by comparing two populations of MS patients, clinically isolated syndrome (CIS) and relapsing-remitting (RR-MS), to healthy controls (HC) matched for age and educational level.CIS is the initial presentation in 80% of MS cases. CIS encompasses an acute clinical attack affecting one or more central nervous system sites and converts to RR-MS with a variable rate, from 20% to 80% depending on the presence and the number of clinically silent white matter lesions on MRI. These early stages of MS are characterized by demyelination processes, thought to have a common inflammatory pathological substrate ; the hand order was randomly presented. Each task consisted of four consecutive runs of 60-s: 30 s of rest followed by 30 s of AM  or MM (for the MI tasks). The participants rested or executed AM or MM following an The motor tasks were performed outside the magnet room due to the difficulty in recording the number of mental or actual ball squeezes during fMRI. The executed ball squeezes were counted by the operator, while imagined ball squeezes were mentally counted and reported by the subject at the end of each task. After this step, fMRI experiment started and the same motor tasks were repeated.For each of the four tasks the average of the number of squeezes of the four consecutive runs was calculated. Then, the ratio (AM/MM) was calculated for both hands separately and used to define the Index of performance (IP) as (1-AM/MM), according to Saiote et al. . Thus, a3); (b) sagittal 3DT1-weighted FSPGR ; (c) gradient-echo EPI with 83 volumes for each of the four task-fMRI runs .All subjects underwent MRI at 1.5T , using an 8-channel phased array head coil. The MRI protocol included the following sequences: (a) axial PD-T2-weighted  as previously described . Results were corrected for multiple comparisons with Gaussian random field theory .For the first-level individual general linear model analysis, the On-Off blocks of the task were convolved with the hemodynamic response function and defined as the explanatory variable of interest. Mean signal from white matter and CSF was calculated by segmenting T1-weighted images with FAST, then registering the resulting white matter and CSF masks to functional space and, finally, averaging the raw time series within each mask. These were added as confound explanatory variables as well as the six motion parameters calculated during motion correction. One contrast was defined to obtain individual maps of activation related to each of the four tasks: AM_R, AM_L, MM_R and MM_L. For higher-level analysis, mixed-effects models as implemented in FSL FLAME were used to model one-sample Post hoc differences were assessed by means of Newman–Keuls tests, and the level of significance was set at P < 0.05. A linear regression model was applied to evaluate the relationship of KVIQ, right and left IP with the other behavioral variables . Linear correlation was used to better characterize the groups differences between behavioral parameters and MRI metrics.Statistical analysis was computed using STATISTICA 7.1 . To evaluate if data were normally distributed the Shapiro-Wilk test was performed for IP and all demographic  and behavioral  variables and for each group separately. ANOVA or nonparametric Mann-Whitney test were used for between-group comparisons for each variable. P = 0.17 and P = 0.09 respectively). The EDSS score was significantly higher in RR-MS patients  than in CIS patients . The ANOVA test, corrected for age, gender and educational level for SDMT, MFIS, 9HPT and KVIQ, did not show any statistically significant difference among groups. Groups showed similar values of SDMT  and MFIS . The 9HPT score was significantly longer (P < 0.05) in the RR-MS (mean 21.36 ± 4.50 s) than in the CIS (mean 18.93 ± 2.99 s) and HC  = 3.30, P < 0.05) group. All subjects rated their imagery vividness as good . No significant relationships between KVIQ and behavioral variables were found, for each single group, for all the patients if considered as a single group (RR-MS and CIS together) and for all participants together  as demonstrated by the linear regression model.Thirty-seven MS patients, 20 with RR-MS  and 17 with CIS , and 20 HC  were prospectively enrolled. Age and educational levels were normally distributed and there was no statistically significant difference between the three groups of subjects (ANOVA: P = 0.001). Moreover, the number of lesions in the CST was significantly higher in RR-MS  compared to CIS patients . A positive correlation between the number of lesions in the left CST and right 9HPT (P = 0.002) and between right CST and left 9HPT (P = 0.011) was found for RR-MS, whereas no correlations were found for CIS group.As expected, given the different disease course and duration of the RR-MS and CIS groups, T2 hyperintense lesion volume (T2LV) was significantly higher in RR-MS  compared to CIS patients  = 5.86, P < 0.05) and hand  = 5.01, P < 0.05). Post hoc analysis showed significant differences between RR-MS group (mean 0.56 ± 0.45) with respect to CIS (mean 0.34 ± 0.26) and HC  independently of the hand and between right and the left hand  independently of the group. Although no significant interaction between group and hand was found, as reported in previous results . IP increased with the worsening of the disease course revealing a progressive anisochrony in the ability to simulate actions . IP for the dominant and non-dominant hand was normally distributed in all the groups. ANOVA analysis, performed with group as a between-subject factor and hand as a within-subject factor, revealed a main effect of group  or for all participants together  as demonstrated by the linear regression model.All groups activated an extensive motor network during AM with the right and left hands, including the contralateral M1, S1 and superior parietal lobule (SPL), SMA, bilateral lateral PM, contralateral thalamus, bilateral putamen and cerebellum. Activated clusters were more extensive in RR-MS patients than CIS patients and HC, and in CIS patients compared to HC, in agreement with the literature . This design require prolonged attention that may have led to a slowdown in the mental motor simulation and a consequent overestimation of movement duration during mental execution  and motor areas deputed to movement preparation, selection  and execution (M1), defining a pattern of activation similar to that shown by RR-MS patients during MI with dominant hand. Moreover, CIS with respect to RR-MS patients showed more activation of putamen, interconnected with many other structures to control many motor skills such as, for examples, motor learning, motor preparation and movement sequences. Results suggest that more challenging is the task, more difficult the recruitment of compensatory brain areas, with a consequent deficit in behavioral performance. Thus, the neuroimaging results may explain the differences found in anisochrony among groups and between dominant and non-dominant hand.These considerations are further supported by results from voxelwise correlation analysis and comparison between MM and AM. The former showed that, during MI with right hand, increased activity in sensory areas correlated with the increment of IP in the whole patient group. Moreover, worse performance according to the IP correlated with activations in cerebellum and several frontal areas usually involved in motor control in RR-MS group. In addition, voxelwise correlation analysis confirmed the shift of activation depending on the disease stage and complexity of the task. Indeed, for non-dominant hand increased cerebellar activations was again associated with higher IP in RR-MS, whereas a relationship between IP and controlateral frontal regions  was observed in CIS group when considered alone; negative correlations with other regions involved in motor control were found in ipsilateral frontal areas  and basal ganglia . The associations between IP and MI activation in the patient groups are more distributed and distinct from those previously observed in healthy participants, where worse performance was associated with higher activation in the left superior parietal lobe and better performance was related to increased right prefrontal cortex recruitment (Saiote et al., Similarly, the comparison of MM and AM showed that CIS patients activated a more extensive MI network than HC for both dominant and non-dominant side, involving frontal, parietal and subcortical regions. Moreover, they showed a higher activation difference between MM and AM with respect to RR-MS group in regions sub-serving sensory processing and higher level functions. RR-MS differed from HC group in MI with dominant hand principally activating brain structures mainly involved in motor control, whereas, as expected from above considerations, no differences were found between these two groups for the non-dominant hand.In conclusion, we found that MS patients with different disease courses showed different pattern of neural engagement during MI and that the networks of brain activations depended on the hand used to execute/imagine the movement. The association between brain activations and anisochrony is reflected in the IP suggesting that it could be considered as a personalized measure of actual and mental execution performance, correlated with disease severity. Therefore, due to the MS impact on motor and cognitive domains already after the first attacks, an indicator such as the IP, taking into account not only motor performance but also cognitive and mental aspects, could be useful as a surrogate behavioral marker of MS severity, especially in the early stages of the disease.AT and CS: substantial contribution to the conception, design, acquisition, analysis and interpretation of the work; drafted and then revised the work after the revision of the coauthors; finally, approved the version to be published; agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. GBr, CC, MAB and GLM: substantial contribution to the interpretation of the work; revised the work; finally, approved the version to be published; agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. GBo and LR: substantial contribution to the acquisition and analysis of the work; revised the work; finally, approved the version to be published; agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. MI: substantial contribution to the conception, design, acquisition, analysis and interpretation of the work; revised the work; finally, approved the version to be published; agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.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.