Evaluation of Antioxidant, Lipid Peroxidation and Toxic Effects after Pomegranate Intake in Healthy Human Volunteers

Introduction: Health care system structure is prone to human error. Medical errors are one of the major challenges that health systems in all countries are grappling with to minimize and reduce the damage caused by them. The aim of this study was to assess the Patient Safety Attitudes, Skills, Knowledge and Barriers Related to Reporting Medical Errors by Nursing Students in Ilam, Iran. Methods: A cross-sectional mixed method was conducted to this study. Sampling was conducted by census of all students entering nursing criteria in Ilam in 2016. A number of 140 students participated in this study. The tool used in this study was created by Schnall et al. that measures knowledge, attitudes and skills related to medical errors reporting. Data were analyzed with t test, regression and correlation coefficients and descriptive statistical methods. Results: The results showed that nursing students had a positive attitude with respect to the reporting of medical errors (p = 0.01). They also have the low knowledge to medical errors and reporting them. There were significant differences in all groups and subgroups of knowledge, attitude, and skills (except creating of safety culture subgroup) between the two group’s students. Moreover, the main reason for not reporting was the lack of knowledge and fear of punishment. Conclusions: The results of this study help those who involve in the health care system to improve patient safety and improve the process of reporting medical errors by nursing students’ participation in the process of reporting error, while improving knowledge and attitudes through nursing How to cite this paper: Safarpour, H., Tofighi, M., Malekyan, L., Bazyar, J., Varasteh, S. and Anvary, R. (2017) Patient Safety Attitudes, Skills, Knowledge and Barriers Related to Reporting Medical Errors by Nursing Students. International Journal of Clinical Medicine, 8, 1-11. http://dx.doi.org/10.4236/ijcm.2017.81001 Received: November 21, 2016 Accepted: January 17, 2017 Published: January 20, 2017 Copyright © 2017 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
Health care system structure is prone to human errors. Medical errors are one of the major challenges that health systems in all countries are grappling with to minimize and reduce the damage caused by them. Studies show that 3 -17 percent of patients admitted to hospitals suffer an injury or condition that occurs as a result of medical errors or adverse event [1]. According to the Institute of Medicine in 1999, approximate 44 to 98 thousand people have lost their lives as a result of medical errors [2]. In the United States, approximate 400 thousand deaths from medical errors occur annually and medical errors are the third leading cause of death in the United States [3]. Patients are entitled to safe care by health care providers. To prevent and reduce medical errors, health care system as a whole needs to change policies and procedures. Although evidence suggests that recurrence of medical errors can be prevented by the reporting system, but medical errors continue because of the lack of reporting of medical errors. Results of a study showed that 50 to 96 percent of medical errors are not reported. In addition it was shown that 96% of medical errors are not evaluated or their recurrence in the future is not prevented [4]. Many studies were conducted on the use of medical errors reporting systems and barriers associated with these systems by nurses. Barriers identified by the nurses include: the completion of error reporting time, lack of knowledge about the occurrence of error, belief in the need to report an error, providing an error as reality or denial, embarrassment or fear of punishment for error reporting [5] [6]. Various studies have linked the lack of knowledge regarding the reporting of medical errors as common barrier. According to the Department of Health and Human Services, the hospital staff does not report 86 percent of medical errors, partially due to inadequate understanding of that what damage can happen to their patients by failing to report [7]. Medical errors reporting system should take priority in accordance with health care providers training and evaluation report. Understanding and identifying reporting errors and barriers to it can help to increase the percentage of reporting medical errors. There will be strong and effective changes in the attitudes and behavior of employees, if provided with repeated and reinforced education [8]. Nursing education programs should include medical errors reporting training to introduce them repeated in and increased use of errors reporting system. Cooper in 2012 stated that introducing errors reporting system in the early years of education could reduce barriers to reporting and improve the error reporting [9]. Health care providers can be very effective to reduce the number of errors that occur by using error reporting system [10]. It is estimated that each year over three million preventable adverse events occur in hospitals [11]. Knowing the underlying causes of these errors is necessary to prevent a repeat occurrence of similar incidents. However, to understand the root causes of such errors, first, in most cases, the error should be repeated. The potentially harmful nature of these errors, the number of medical errors that occur in hospitals is unacceptable. Thereby reducing the incidence of medical errors must be a priority to improve patient safety [12]. The evaluation of reporting barriers in reporting systems is a fundamental step to reduce medical errors and improve patient safety. Nursing students are key beneficiaries in an effort to reduce medical errors with the ability to help to improve medical errors reporting systems. Promote clear understanding of medical errors and barriers to reporting are essential to develop effective measures to increase the use of error reporting systems. Therefore, the objective of this study is to understand the barriers to reporting medical errors by nursing students.
Hospitals and other health service providers must take action to improve the reporting of medical errors and improve quality of care through learning from mistakes. In general, the reporting of medical errors should become a culture in health care centers, and this is to boost the use of error reporting systems by reducing the fear of punishment. Many studies have examined barriers to reporting of medical errors through physician and nurses perspectives, however, few studies conducted on the barriers to reporting and perception of medical errors by nursing students. Therefore, awareness of the importance of reporting medical errors should be started during nursing education. All health care professionals, including nursing students are required to report medical errors. Balas et al. (2004) studied 393 nurses and showed that 30 percent of nurses have reported at least one error [13]. Nursing students may have much concern for various reasons to report a medical error; however, the attitude towards the reporting of medical errors could be affected through appropriate education and creating culture of reporting .Knowing the barriers to use medical error reporting systems by students can help the importance of nursing education in promoting the safety culture [14]. Yaghobi et al. (2015) results titled "The incidence of medication errors in nursing students and their views on not reporting the error among senior nursing students" using a questionnaire containing 17 statements about students' demographic characteristics and causes of not reported medication errors in the three domains of fear of the consequences of reporting, management factors and reporting factors show that among the aspects surveyed the higher score went to reporting factors, that forgetting the medication errors reporting by students accounted for most points. Given the domains of fear of the consequences of reporting medication errors by a student the fear of news dissipation in the faculty and among other students gained the higher score. Moreover, in the area of management factors higher scores went to the disproportionate instructor's reaction to the severity and importance of errors in reporting and forgetting the medication errors reporting by students. Also fear of news dissipa-H. Safarpour et al.
tion in the faculty and among other students, absence of a precise definition of medication errors, fear of informed the physician and blamed by them, fear of error detection and legal problems followed, and unimportance of medication errors reporting from the perspective of students were the five main causes of not reported medication errors by students in terms of single causes of not reported medication errors by nursing students [15]. Another study (2012) was conducted to examine the causes of not reporting medical errors from the perspective of nursing managers, supervisors, and head nurses in all clinical wards of a hospital. In this study the causes of not reporting medical errors has been classified in four categories. Results show fear of punishment by direct supervisor, high workload the individual exposed to charge and considering error reporting as useless were of great importance. Also created extra work for the person (to report) and loss of reputation or job were of the utmost importance from both groups perspectives. The cost of ineffective reporting from the supervisor's perspective gained the least importance, but was of the utmost importance from head nurse perspectives. Moreover, the possibility of cancelling the employment contract was of the most importance on the view of supervisors, but with the least importance on the view of head nurses [16]. Another study examines barriers to reporting by nurses and doctors to modify the this behavior, The questionnaire used in the study also showed that barriers to reporting and lack of adequate knowledge and allowed researchers to determine the most adjustable barriers.The barriers include structure and process as well as lack of knowledge [6]. According to the authors study, specifically, the use of questionnaires is the most common method to study the reporting barriers. Healthcare Research and Quality Agency proposed two different tests to evaluate the overall safety culture in 2012: Examination of patient safety culture and safety attitudes questionnaire [17]. While these tests help to determine the perceived safety of health care, none specifically assess knowledge. Many studies have reported a lack of knowledge as a barrier in medical errors reporting [18] [19]. As a result, to add knowledge assessment, as part of future studies to examine barriers to reporting medical errors by nursing students is important. Therefore, the aforementioned study should be modified to be used in this study and knowledge assessment should be added as part of this tool. One of the developed tools that added knowledge assessment as part of the evaluation is Schnall

Methods
A cross-sectional mixed method (quantitative and qualitative) was conducted to this study. Sampling was conducted by census of all students entering nursing criteria in Ilam in 2016. A number of 140 students participated in this study, 18 of whom were Master of Science in nursing student (MSN) and 122 were Ba-chelor of Science in nursing student (BSN). Inclusion criteria included: students who passed at least one course of clinical practice in a hospital environment. The exclusion criteria were dissatisfied students, freshmen without hospital and clinical backgrounds. The tool used in this study was Patient Safety attitudes, skills and knowledge scale (PS-ASK) that created by Schnall et al. (2008). This tool has been created for use in nursing programs and therefore was suitable to examine the study variables. This tool items were based on five-scale Likert including three content groups including knowledge, skills and attitude. Attitude scale consists of 9 items and was divided into three subgroups of error detection, time investment and creating a culture of safety. Literature has determined that attitude, as lack of knowledge is a common barrier to medical errors reporting [21] [22] [23]. Skills scale consists of 13 items and was divided to the subgroups of error analysis, decision support technology, and threats to patient safety. Knowledge scale consists of 4 items. However, this tool was not able to measure some barriers to reporting medical errors which could affect the nursing students such as understanding the need to report the error, fear of punishment or fear of creating a problem for the another; therefore to get more information an open-ended questions was added to the questionnaires study other barriers [19].
The open-ended question was "Is there anything that may prevent you from completing an error report after a near miss or adverse event occurs?" First, the questionnaire was translated into Farsi by two people fluent in English. Then to match it with the English questionnaire was translated into English by two linguists. Content validity test was used to check for validity. The tool was handed to 10 college experts. After examining the content validity, the index of 0.87 was reported. To pilot test, 30 questionnaires were distributed among 30 samples and after 10 days the test-retest was conducted. Cronbach's alpha coefficient was measured after data was collected using SPSS 21 software. Alpha coefficient of 0.81 was calculated in this study. All parts of the questionnaire data and qualitative open-ended question were analyzed separately. After data collection, data analysis was performed using the SPSS v.19 software. Descriptive statistics were calculated. Normality of data distribution was confirmed by Kolmogorov-Smirnov test. Then, data was analyzed with t test, regression and correlation coefficients and descriptive statistical methods. Significance as well as P ≤ 0/05 was determined.

Results
The number of 140 students participated in this study, 12.9% (n = 18) were MSN student and 87.1% (n = 122) were BSN students. Table 1 shows the demographic characteristics of nursing student in this study.
The mean and standard deviation were compared based on two groups of BSN and MSN students with inclusion criteria. Table 2 shows the overall scores of attitude, skills and knowledge and associated subcategories. The results showed that students' attitudes about medical errors were higher among MSN student. Also, there was a significant difference between skill category especially in the threats to patient safety subcategory in both groups (p = 0.0001) and MSN students showed higher confidence and were able to provide and improve patient safety. Table 3 outlines the differences between the two student groups in each category and subcategory. There was no significant difference between the creating a culture of safety in both groups (p = 0.43). Also there is statistically significant difference in the subcategory of error detection in the skills category and MSN students' attitudes were more in error detection (p = 0.0001). In addition, results showed that there was a significant difference between the two groups in terms of knowledge and the knowledge of MSN students was more (p = 0.007). There was a negative statistically significant relationship between the two subcategories of creating a culture of safety and error detection (p = 0.034, r = −0.7) (Figure 1). Also There was a negative coefficient correlation between the creating a culture of safety and knowledge and students whose attitudes were more toward creating a culture of safety had less knowledge about the safety of patients (p = 0.003, r = −0.6). These results show the important effects of creating a culture of safety. The highest positive response went to the error detection and the highest negative response was to creating a culture of safety. This shows that students' attitude was more toward creating a culture of safety and less toward errors detection. In addition, results showed that most students understand  Statements, such as fear of punishment and errors detection, may be followed with problems reflects the punitive culture of nursing environment. Skills gained lower scores than other aspects, and students were at lower levels of competency in the risk analysis subgroup. Nurse's knowledge on understanding of medical errors and reporting them was low. Overall findings showed that students are afraid of reporting errors and lack enough knowledge, thus requiring reporting systems trainings.

Conclusion
Improving patient safety should be the goal of all health care professionals which should start as a strong base of experience and education of professional health care specialists. The current study emphasis is on medical errors reporting and patient safety that should be included in nursing training programs. The study showed nurses lack of knowledge and attitude in relation to patient safety.
Nursing programs may be somewhat improved the situation, but students will not acquire adequate skills and knowledge as long as nursing education is not based on a model and purposeful. Although there are processes in reports of medical errors, nursing students are not involved in this process and, therefore,

Introduction
Epidemiologic studies have shown significant inverse relationship between the incidence of various diseases and dietary intake of fruits and vegetables [1]. Free radicals have been implicated in the pathogenesis of many diseases. There is a growing evidence that excessive production of free radicals can cause or exacerbate many human diseases [2] [3]. Pomegranate has been used in folk medicine from ancient times owing to its potential health benefits [4]. The various phytochemicals present in this fruit are potent antioxidants and anti-inflammatory agents, thereby counteracting oxidative damage and inflammation which is responsible for the pathogenesis of various diseases [5] [6] [7]. The antioxidant property of pomegranate juice was shown to be three times higher than that of red wine and green tea based on the evaluation of the free radical scavenging and iron reducing capability of the juices [5]. It possesses significantly higher levels of antioxidants in comparison with the commonly consumed fruit juices [8] [9].
The major antioxidant polyphenols present in the pomegranate fruit include the ellagitannins and anthocyanins [10]. Punicalagin is the major ellagitannin present in the fruit [11]. Clinical studies with relation to this fruit are comparably lesser with that of animal trials. As there are only limited, but promising human data, the present study aimed to further strengthen support for the unique antioxidant and antiperoxidative properties of this healthy fruit. The primary objective of this study was to evaluate the circulatory levels of selected antioxidant and lipid peroxidation marker in healthy human volunteers before and after pomegranate intake for a period of 0 -90 days. As the secondary objective of the study, we also assessed the toxic effects of pomegranate supplementation by determining hepatobiliary and renal function tests.

Materials and Methods
The work has been carried out at the Dept. was fixed in such a manner that prior to this study another trial was conducted in which varying doses of pomegranate were given to healthy human volunteers, the varying doses were 50 g/day, 100 g/day, 150 g/day and 200 g/day out of these groups a a significant percentage difference in antioxidant activity and antiperoxidative activity were shown in groups which consumed at least 100 g/day and more, so in this study 200 g/day was given, which showed maximal activity among the varying dosages used for the study in the previous trials. Participants suffering from any diseases/disorders that may interfere with the study were excluded. 5 mL of blood sample was taken for the analysis. Study was designed for a period of 90 days. Blood samples were collected before the intake, 45 days after the intake and 90 days after the intake of fresh pomegranate fruit at a dosage of 200 g/day. Serum/Plasma was separated and estimated using the standard methods. The major enzymic antioxidants analysed were Catalase (Maehly and Chance) [13], Glutathione reductase (Goldberg and Spooner) [14] and glutathione-S-transferase (Beutler) [15]; the major non-enzymic antioxidants determined were glutathione (DTNB) [16], Vitamin C (2,6-Dichlorophenol Indophenol) [17] & Vitamin E (Baker & Frank) [17]. The lipid peroxidation marker estimated was Malondialdehyde (Beuge et al.) [18]. For determining the toxic effects of the fruit, if any, Hepatobiliary function was assessed by determining the levels of Total Bilirubin (Jendrassik & Grof) [19], Total Protein (Biuret) [20], Albumin (BCG) [20], Globulin (Friedwald's formulae), AST (UV, Kinetic) [21], ALT (UV, Kinetic) [21] and ALP (pNPP-AMP) [21]; Renal function was assessed by estimating the levels of Urea (GLDH-Urease) [22], Uric acid (Uricase/peroxidase) [22] and Creatinine (Jaffes) [22] according to the methods mentioned in the parenthesis by authors names. The data was analysed by using sigmaplot 13 version. P < 0.05 that was treated has statistically significant.

Results
Inter group comparison of serum SOD levels ( Table 1 & Table 2) shows a statistically significant increase between Group Ia and Ib (P < 0.003) with a highly significant increase between Group Ia and Ic & Group Ib and Ic (P < 0.001). The percentage increase was more in between Initial and final levels followed by Mid and final level & Initial and Mid level in the order 12.8 > 8 > 4.4.
Inter group comparison of serum CAT levels ( Table 1 & Table 2) shows a statistically significant increase between Group Ia and Ib (P < 0.049) with a highly significant increase between Group Ia and Ic & Group Ib and Ic (P < 0.001). The percentage increase was more in between Initial and final levels followed by Mid and final level & Initial and Mid level in the order 62.4 > 37.9 > 17.7.
Inter group comparison of serum Glutathione peroxidase levels ( Table 1 &   Table 3) shows a statistically significant increase between Ib and Ic (P < 0.005) with a highly significant increase between Group Ia and Ic (P < 0.001). The percentage increase was more in between Initial and final levels followed by Mid Inter group comparison of serum Glutathione reductase levels (Table 1 &   Table 3) shows a statistically significant increase between Ib and Ic (P = 0.005) with a highly significant increase between Group Ia and Ic (P < 0.001). The percentage increase was more in between Initial and final levels followed Inter group comparison of serum Glutathione S transferase levels ( Table 1 &   Table 3) shows a statistically significant increase between Ib and Ic (P = 0.049) with more significant increase between Group Ia and Ic (P = 0.004). The percentage increase was more in between Initial and final levels followed by Mid and final level & Initial and Mid level in the order 11.3 > 7.4 > 3.6. Eventhough there is no statistically significant change between Group Ia and Ib there is a difference in the mean percentage increase of value.
Inter group comparison of serum Glutathione levels ( Table 4 & Table 5) shows a statistically significant increase between Ib and Ic (P = 0.01) with a highly significant increase between Group Ia and Ic (P < 0.001). The percentage increase was more in between Initial and final levels followed by Mid and final level & Initial and Mid level in the order 21.0 > 12.5 > 7.5. Even though there is no statistically significant change between Group Ia and Ib there is a difference in the mean percentage increase of value.
Inter group comparison of serum Vitamin C levels ( Table 4 & Table 5) shows a statistically significant increase between Ib and Ic (P = 0.001) with a highly sig- Inter group comparison of serum Vitamin E levels ( Table 4 & Table 5) shows a statistically significant increase between Group Ia and Ib (P = 0.001), with a highly significant increase between Ia and Ic & Ib and Ic (P < 0.001). The percentage increase was more in between Initial and final levels followed by Mid and final level & Initial and Mid level in the order 25.7 > 17.8 > 8.5.
Inter group comparison of serum MDA levels ( Table 4 & Table 6) shows a statistically highly significant decrease in all groups studied (P < 0.001). The mean percentage decrease was more in between Initial and final levels followed Inter group comparison of Liver function parameters viz; serum Total Bilirubin, Total Protein, Albumin and Globulin, AST, ALT, ALP (Table 7, Table   8, Table 9 & Table 10) and renal function parameters viz; Blood urea, serum uric acid and creatinine (Table 11 & Table 12) were statistically insignificant in all groups studied, showing that supplementation of pomegranate does not have any toxic effects for the organs liver and kidney.

Discussion
Dose effects of supplementary feeding of Pomegranate in healthy human volunteers show that all enzymic and non-enzymic antioxidant levels were raised in the blood significantly for both 45 days and 90 days of feeding without any observable toxicity. When we consider the effect of feeding highly significant dose effects were observed in the group who were served pomegranate for 90 days.
Pomegranate fruits used in this experiment are fully enriched with several antioxidants such as phytosterols, polyphenols, flavanoids, carotenoids and Vitamins especially E & C [9] [10]. In addition to the above, several minerals such as iron that promote synthesis of haemoglobin and selenium,that promotes glutathione peroxidase action are also there in this fruit. The finding that 90 days of feeding with pomegranate was more effective than 45 days may be due to the fact that the human body cells are more exposed to the antioxidants enriched components of the fruit. Pomegranate contains antioxidants such as anthocyanins, ellagic acid, gallic acid, punic acid, catechin, EGCG, quercetin, rutin, apigenin and other flavanoids ellagitannins and triterpenoids such as ursolic, merlinic and ariatic acids, out of which EGCG is the strongest antioxidant with eight hydroxyl groups and this may be the reason that pomegranate activates the enzymic and nonenzymic antioxidants of the body and reduces lipid peroxidative effects.

Conclusion
The study has shown that consumption

Methods
Data for the current study was extracted from the NIS database, a part of the Board. This is a retrospective study using data extracted from the NIS database.
No specific patient identifiable information was utilized, and no patient consent form was required.

Demographic Characteristics
The mean age for all patients who underwent PCI for ACS was 64 ± 12 years (

Clinical Outcomes
Patients who developed aortic dissection had a longer LOS, compared to those who did not (9 ± 12 days vs. 3 ± 4 days, p < 0.001) (

Discussion
Aortic dissection is a rare complication following PCI. Although PCI was not performed until 1977, iatrogenic aortic dissection following open-heart surgery was first reported in the 1960s [6] [7]. In a recent single-center retrospective study over a 14-year period published by Leontyev et al. (2012), the incidence of iatrogenic aortic dissection was reported to be 0.06% following other cardiac surgical procedures and 0.01% following cardiac catheterization procedures [3].
In the current study, aortic dissections occurred in 0.05% of the PCI cases following ACS with an in-house mortality of 13.2%. These results are consistent with more recent PCI studies, which have reported incidence rates ranging from 0.02% to 0.07%, with mortality rates as high as 50% [ [15] [16]. The relationship between the role of atherosclerosis and the velocity of the retrograde flow, more specifically a forceful contrast injection into the false lumen, has been suggested as an additional or concurrent mechanism for aortic dissection following PCI [10]. A high velocity retrograde jet may disrupt diseased intima at the tip of the cannula at the time of cannulation or later during the perfusion [7]. Registry of Acute Aortic Dissection (IRAD), which reported that aortic dissections were less frequent in females, however, females who did develop aortic dissection were significantly older than men [19]. These findings suggest there should be a greater suspicion for the possibility of aortic dissection following PCI in these high-risk patients.
In addition to age and gender, the implication of PVD in the incidence of aortic dissection following PCI has been discussed. Patients with PVD had a 129.2 times higher chance of developing aortic dissection. In a study of 48 patients who developed aortic dissection following PCI by Leontyev et al., 22.9% of patients had a history of PVD [3]. In addition to PVD being a risk factor for aortic dissection, 47.9% of patients had New York Heart Association (NYHA) class III/IV symptoms, and 33.3% of patients had a left ventricular ejection fraction (LVEF) <50% [3]. Multivariate analysis indicated coronary malperfusion and preoperative NYHA class IV symptoms as being independently associated with early mortality [3].
Diagnostic imaging for aortic dissection is used to rapidly confirm or exclude the diagnosis, and classify the extent of the dissection. Computed tomography (CT) is used in 61% of cases, while echocardiogram is used in 33%, magnetic resonance imaging (MRI) in 4%, and aortography in 4% [14] [20] [21]. Transthoracic echocardiography (TTE) can be beneficial in identifying proximal aortic dissections in emergent cases with unstable patients, and confirmation of the diagnosis often requires more than one non-invasive imaging study [14].
In addition to current imaging, the diagnostic biomarkers which permit the early detection of aortic dissection have been investigated. Circulating smooth muscle myosin heavy chain protein, which is released from damaged medial smooth muscle of the aorta, has been shown to be elevated in the initial hours of an acute dissection [14] [22]. In a review studying the circulating biomarkers available for the diagnosis and prognosis stratification of aortic dissection, Morello et al. (2014) reported that the variation in the range of biomarkers of aortic dissection could potentially be used as a tool to screen symptomatic patients, to identify patients at higher risk of aortic disease, to rule out aortic dissection with low clinical probability of aortic dissection and/or to obtain prognostic stratification of affected patients [22]. Acute phase reactors such as C-reactive protein,  [20]. While surgical resection or stenting of the ascending aorta and possibly the aortic arch is considered the gold standard treatment for dissections involving the ascending aorta; this has also been extended to patients with iatrogenic aortic dissections [24].
In this study, aortic dissections occurred most often following PCI for unstable angina compared to STEMI and NSTEMI. The decrease in incidence and mortality rate after aortic dissection following PCI reported in the current study may be attributable to improved recognition of aortic dissection as a complication after PCI and advancements in PCI procedures [3]. Drug-eluting stents, have been shown to significantly reduce the rate of in-stent revascularization, but has been associated with increased rates of late stent thrombosis [25]. given to the patients. Despite these limitations however, the NIS includes data from 1000 different hospitals in the US and more than 700,000 patient records were obtained for this study, and is likely a diverse enough sample to be able to generalize across most US hospitals in terms of delivery of care.

Conclusion
Aortic dissection is a rare but potentially lethal complication after PCI for ACS, which occurs most commonly in older patients admitted from the ER with Me-dicaid insurance. Aortic dissection is associated with significantly worse outcomes including longer lengths of stay, and higher rates of mortality, ventricular

Introduction
Despite significant progress in studies on PD, etiopathogenic processes cannot be clearly defined. One of the important processes in the pathogenesis of PD is oxidative stress [1]. Oxidative stress can be described as the impairment of cell glutathione, and γ-glutamylcysteine [8]. Thiol groups of proteins are oxidized by oxidant molecules and reversibly converted to disulfide bond structure. Disulfide bond structure can be again reduced to the thiol group. Maintenance of the thiol-disulfide homeostasis is kept by conversion of disulfide bond structure to the thiol group. When the native thiol levels decrease, disulfide levels increase [9].
Thiol-disulfide homeostasis has an important role on antioxidant protection, detoxification, apoptosis, stabilization of protein structure, regulation of protein function, cell signaling and transcription [6]. While only the thiol levels were able to be measured since 1979, a novel and colorimetric, automated method was developed by Erel and Neselioglu so that the thiol and also the disulfide levels can be measured one by one [9] [10]. Abnormal thiol-disulfide homeostasis state is related to the pathogenesis of different diseases, including diabetes mellitus [11], cardiovascular diseases [12], cancers [13], neurological diseases [14] [15], liver diseases [16] and chronic renal failure [17].
There is no study in the literature showing the relationship between PD with the thiol-disulfide homeostasis. The aim of our study is to investigate the thioldisulfide homeostasis in patients with PD.

Material and Method
Totally Patients were excluded from the study if they met one or more of the follow-ing criteria: hypertension, heart and cerebrovascular disease, diabetes mellitus, hepatic or renal failure, autoimmune diseases, active infection, active or chronic inflammatory diseases, smoking, obesity, collagen tissue disease and treatment with antiinflammatory, antioxidant or immunosuppressive medications, malignity, alcohol and substance abuse or dependence, vitamin supplements. Sociodemographic data form was completed to the participants.
Antecubital vein blood was taken after 12 hours of fasting from the participant. Vacutainer gel tubes were used. Serum was separated by centrifugation 10 min at 4000 rpm, at 4˚C and rapidly serum fractions were stored at −80˚C.
A new and fully colorimetric automated method developed by Erel et al. was used for the measurement of plasma native thiol, total thiol and disulfide levels based on the reduction of dynamic disulfide bonds to functional thiol groups.
Native thiol content was subtracted from the total thiol content; half of the obtained difference provides the disulfide bond quantity. Disulfide/thiol ratio, disulfide/total thiol ratio and thiol/total thiol ratios were calculated automatically [9].

Statistical Analysis
In the statistical evaluation of the data, the statistics package for social sciences (SPSS) Version 18.0 computer package program was used. The results were presented as mean ± SD. The differences between groups were determined by student's unpaired t-test and Mann Whitney U-test. Pearson correlation coefficient was used to assess correlations. Distribution of continuous variables was assessed with Kolmogorov-Smirnoy. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of native thiol, total thiol, disulfide/native thiol and disulfide/total thiol. Using the ROC curve, the responsiveness is described in terms of sensitivity and specificity. Values for sensitivity and for false-positive rates (1-specificity) are plotted on the yand the x-axes of the curve and the area under the curve represents the probability a measure correctly classifies patients as improved or unchanged. P values less than 0.05 was accepted as the significance level.

Results
The mean ages among the PD group (15 male, 37.5%) were 39.9 ± 14.4 years, and the mean ages of the control group (20 male, 50%) were 38.2 ± 13.6 years.
The age and gender distributions were similar in both groups (p = 0.594, 0.260, respectively).
The laboratory findings of the control and PD groups are in Table 1. Native and total thiol levels were significantly lower among the PD group relative to the control group (p < 0.001). There was no significant difference between the control and the PD groups in terms of disulfide levels (p = 0.261). While the native thiol/total thiol ratio was decreased in the patient group (p < 0.001), disulfide/ native thiol and disulfide/total thiol ratios were elevated in the patient group (p < 0.001, p < 0.001 respectively).
ROC analysis of area under the curve, cut-off levels, and sensitivity and specificity values are given in Table 2. The AUC for the Native Thiol and Native Thiol/Total Thiol ratio were 0.855 and 0.793 respectively.
ROC analysis was used. ROC curves of all parameters are seen in Figure 1.
The sensitivity and specificity of Total Thiol were 80% and 87.5%, respectively, and the AUC was 0.837.

Discussion
The    found the GSH-Px, SOD and MDA levels to be significantly higher in the PD group compared to the control group [19]. Another study has again evaluated oxidative and anti-oxidative parameters in PD. Oxidants (adenosine deaminase (ADA) and XO levels) were higher in the patient group than the control group in this study but there was no significant difference regarding antioxidant parameters [20]. Although many important findings have been revealed by studies on oxidative and anti-oxidative PD etiology [19] [20], oxidant-antioxidant homeostasis of PD has not been fully elucidated, yet.
The thiol-disulfide homeostasis plays a role in the cellular functions. The thiols are the primary target for oxygen radicals which are non-enzymatic antioxidant molecules taking an important part in preventing damage caused by free radicals [21]. The extent to which the proteins are affected from free radicals is related to their amino acid content. Molecules containing unsaturated bonds and SH groups and proteins releasing amino acids such as homocysteine, methionine, cysteine, tryptophan, tyrosine, phenylalanine, and histidine can be more easily affected by free radicals [22] [23]. Thiol-disulfide homeostasis, which was first measured in 1979, could be only measured in one direction [10]; however, a novel, automated and colorimetric method developed in 2014 by Erel et al. which allows the measurement of the homeostasis in either direction. Erel et al.
reported that disulfide levels were higher in patients with diseases such as diabetes, in smokers, obese patients, premature ovarian failure, subclinical hypothyroidism and were lower in patients with proliferative diseases, such as urinary bladder cancer, renal cancer, non-small cell lung cancer and multiple myeloma [9]. This is the first study in the literature to evaluate thiol-disulfide homeostasis in patients with PD. The present study found decreased levels of native thiol, total thiol, and native thiol/total thiol ratio and increased disulfide/native thiol and disulfide/total thiol levels in the patient group, compared to the control group.
These finding suggest that thiol-disulfide homeostasis has shifted toward disulfide direction in PD patients. Decreased thiol levels indicate a problem in antioxidant system in PD patients. According to our data, the cut-off value was 353.1 µmol/L, 393.8 µmol/L, 92.26 (%), 3.83 and 3.56 for native thiol, total thiol, native thiol/total thiol, disulfide/native thiol and disulfide/total thiol level respectively. The patients with serum native thiol, total thiol and native thiol/ total thiol levels below these sills must be particularly evaluated for PD. The evaluation can be made by the automated measurement of these values.
Although the increase in disulfide molecules generated by oxidation of thiol groups in the patient group was not statistically significant, increased disulfide/ native thiol and disulfide/total thiol levels suggested increased oxidative stress in PD patients. The deficiency of a significant increase in disulfide levels in the PD group can be explained by the lack of stability in the thiol-disulfide homeostasis and the fact that this balance is affected by kidney and liver functions [24].
This study is cross sectional so we think that this is the main limitation. The sample size of the patient and control groups may be another limitation.

Conclusion
The present study investigated thiol-disulfide homeostasis using a new, colorimetric, and automated method in PD patients. Our study results showed that serum thiol levels were lower and disulfide/total thiol levels were higher in PD patients, compared to the controls. These findings also highlight the importance of oxidative stress in the etiopathogenesis of PD. We believe that further studies investigating the effects of SH-containing anti-oxidant components on thioldisulfide homeostasis and clinical outcomes of PD treatment would make significant contribution to the treatment of this disease.

Abstract
On the South Island of New Zealand, Anaesthetists and other Medical Professionals, frequently refer their patients with Complex Regional Pain Syndrome (CRPS) for physiotherapy management. Beliefs about what is important for the management of patients with CRPS are lacking across all medical and allied health disciplines. Difficulties are no gold standard for diagnosis and evidence for intervention methods is moderate or can be conflicting. This paper explores what Physiotherapists believe to be important in a clinical setting for their management of CRPS, as well as documenting and evaluating their interventional methods used in everyday clinical practice across the region of the South Island of New Zealand. This has not been recorded before. Eightyone Physiotherapists replied to questions on their usual treatment interventions for the management of CRPS, their frequency of use of these treatment interventions, and what they believed to be important in the management of pain and improvement of function. The results demonstrated that CRPS is not a common condition seen regularly by Physiotherapists; that there is a high level of variation between the physiotherapy interventions used and that Physiotherapists' beliefs regarding interventions used for pain management and functional restoration differ. Education was reported as the most frequently used intervention method. Those physiotherapists seeing CRPS patients more frequently are more likely to use evidence based intervention methods like graded motor imagery or sensory motor training.

Introduction
Complex Regional Pain Syndrome (CRPS) is a persistent pain syndrome with a low prevalence [1] [2] which exhibits abnormal sensory, motor, sudomotor, vasomotor, and/or trophic findings and shows variable progression over time [3] [4] [5] [6]. It is evaluated by anaesthetists in Pain Management or by physiotherapists. It can be argued that it is both under-diagnosed [7] and over-diagnosed [8] [9]. Early diagnosis and referral by anaesthetists in Pain Management or by other medical disciplines to physiotherapists is regarded as essential [10]. Professionals are shown to affect practice, for example, as follows: the pain experienced in the elderly can be minimised [11]; physiotherapists will continue to treat low back despite any evidence of improvement [12]; and beliefs about opioid medication affect prescription practice [13] [14].

Purpose
Beliefs about what Physiotherapists in a clinical setting regard as important for their management of CRPS, as well as their beliefs about the interventional methods used in everyday clinical practice across the region of the South Island of New Zealand were evaluated.

Method
There

Statistical Analysis
Standard descriptive statistics (Statistica 7, Microsoft Excel for windows PC) was used to compare categorical variables. Data analysis used ANOVA tests for significance between categorical variables and frequency of consultations with Physiotherapists.

Results
The 64 clinics and hospital outpatient departments who accepted patients with CRPS employed a total of 141 Physiotherapists. The 84 clinics and hospital outpatient departments who did not accept CRPS patients were excluded from the sample. Questionnaires were posted in self-addressed and pre-stamped envelopes (one for each Physiotherapist), or personally delivered. Eighty-one Physiotherapists answered the questionnaire and returned it either personally (n = 5) or by mail (n = 76). This provided a response rate of 57%. Participation rate in the physiotherapy intervention questionnaire is shown in Figure 1. CRPS declined to answer the questionnaire. Reasons given were as follows: no reason given (n = 1); about to retire (n = 1); staff shortages (n = 1); unwilling to have practice scrutinised (n = 2); too busy (n = 1); or an assessment only service (n = 1). The frequency of use of all interventions used is listed in Table 1.
In the group who mostly used GMI, 10% used it in the classic order versus 2% who used it in an ad hoc sequence. However, 43% never used a GMI classic sequence at all. Twenty per cent occasionally used the GMI classic sequence. Fifteen percent of the GMI users often applied the classic sequence. Ten percent of Physiotherapists used the classic sequence of GMI as the most common intervention. Those who used the ad hoc sequence showed similar figures. This is shown in Figure 2.
These data were further analysed using ANOVA tests for significance to determine if the frequency of seeing CRPS patients affected the type of intervention used. The more frequently a Physiotherapist evaluated CRPS patients, the following occurred, namely: 1) they used GMI more often rather than occasionally in the classic order of the 3 phases, p = 0.017; 2) the more they used relaxation techniques often rather than occasionally, p = 0.021; 3) the more likely they were to use SMT, and sensory mapping or discrimination occasionally rather than never, p < 0.001 and; 4) the more often they used oedema massage rather than seldom, p = 0.029. Table 2 outlines the significant differences between those Physiotherapists who evaluated CRPS patients frequently compared to those who seldom saw CRPS patients.   Beliefs about what was considered most effective for the management of CRPS patients proved highly variable. Physiotherapists were almost equally divided about whether or not reducing the pain experience was essential to improve the functioning (51% and 43%, respectively). This is shown in Figure 3.
Eighty per cent believed that improving the function was essential to reduce pain; 14% believed that it was not essential. This is shown in Figure 4.
Physiotherapists were equally divided on their beliefs about exercise and pain being either indicated or contraindicated in CRPS. These beliefs are shown in Figure 5.

Discussion
These data provide the first contribution to literature about a systematic survey of physiotherapy and CRPS management in everyday clinical practice. Half of all New Zealand South Island physiotherapy practices do not manage CRPS patients. Only 10% of the Physiotherapists that manage CRPS patients treat more than two CRPS patients per month. Education was most often used as an intervention for CRPS. This was recorded by 83% of the Physiotherapists who together with Anaesthetists play an important role in education as CRPS patients possess a sub-minimum standard of basic knowledge about the syndrome [25].
Similar to diseases like diabetes, education enables behavioural change as well [26].
The data showed that the more frequently Physiotherapists evaluated CRPS patients, the more likely they were to use interventions with moderate based evidence, such as GMI and SMT. However, GMI and SMT were not used by many other Physiotherapists who evaluate CRPS patients less frequently. It is not possible to determine the reasons for these differences. This clearly needs further investigation. It has been suggested that physiotherapy management for CRPS needs to be specifically personalised [27]. This can be particularly difficult, as CRPS presentations, progression and outcome are variable. There is little specific evidence about what intervention to apply and when [28]?
These data illuminated the inconsistency with which physiotherapy interventions (other than education that is mostly used) are practised by those managing CRPS patients. A third of the sample often used cognitive techniques and breathing control with relaxation techniques; another third used them occasionally. Those treating more CRPS patients are more likely to use the above technique rather than occasionally. Less than 15% are most likely to use these techniques. Eighty per cent are familiar with these interventions but do not apply them regularly.
Beliefs were divided about pain reduction being essential or not for improving the function of the affected CRPS limb. Eighty per cent believed that by improving function, the pain is reduced. Exercising and increasing the pain was a belief supported by 17%. It was found that 49% applied active exercises despite pain, but then only occasionally. When asked whether pain was contra-indicated or not for CRPS exercises, the groups were almost equally divided. Half believed that it was inevitable to have some pain with exercise; only 17% of this group believed that pain with exercise was really necessary.
Holding different beliefs influences the interventional modalities chosen for pain reduction or improvement in function for the treatment of CRPS patients.
It influences the relationship the Physiotherapist has with the referring Anaesthetist. Applying any intervention by one half of Physiotherapists can become potentially difficult, if pain exacerbation is thought to be contraindicated, as pain forms the hallmark of CRPS. There are CRPS patients who present with reasonable function, but suffer severe pain [29]. The clinical presentation of CRPS re- A weakness of the study is the relatively small sample size with potential bias being represented by the 57% response rate. Another weakness of the study is the use of Likert scale for measuring the frequency of the physiotherapy interventions that is not formally validated.
The strength is that this study provides the first evidence to represent data across a region, about Physiotherapist beliefs and usual interventions for CRPS patients. The use of self-reporting questionnaires as a valid measure is supported [34]. Future studies should be undertaken to develop validated questionnaires about beliefs around CRPS for Anaesthetists in Pain Management, Physiotherapists, and other health care providers, as well as for patients suffering from CRPS. It is important to determine how these beliefs influence referral, intervention method(s) and patient outcomes.