Diabetic type 1 patients are often advised to use dose adjustment guidelines to calculate their doses of insulin. Conventional methods of measuring patients' adherence are not applicable to these cases, because insulin doses are not determined in advance. We propose a method and a number of indicators to measure patients' conformance to these insulin dosing guidelines.We used a database of logbooks of type 1 diabetic patients who participated in a summer camp. Patients used a guideline to calculate the doses of insulin lispro and glargine four times a day, and registered their injected doses in the database. We implemented the guideline in a computer system to calculate recommended doses. We then compared injected and recommended doses by using five indicators that we designed for this purpose: absolute agreement (AA): the two doses are the same; relative agreement (RA): there is a slight difference between them; extreme disagreement (ED): the administered and recommended doses are merely opposite; Under-treatment (UT) and over-treatment (OT): the injected dose is not enough or too high, respectively. We used weighted linear regression model to study the evolution of these indicators over time.We analyzed 1656 insulin doses injected by 28 patients during a three weeks camp. Overall indicator rates were AA = 45%, RA = 30%, ED = 2%, UT = 26% and OT = 30%. The highest rate of absolute agreement is obtained for insulin glargine (AA = 70%). One patient with alarming behavior  was detected. The monitoring of these indicators over time revealed a crescendo curve of adherence rate which fitted well in a weighted linear model . This shows an improvement in the quality of therapeutic decision-making of patients during the camp.Our method allowed the measurement of patients' adherence to their insulin adjustment guidelines. The indicators that we introduced were capable of providing quantitative data on the quality of patients' decision-making for the studied population as a whole, for each individual patient, for all injections, and for each time of injection separately. They can be implemented in monitoring systems to detect non-adherent patients. In some diseases such as diabetes, patients manage their own therapy. Insulin dependent diabetic patients are often advised to use dose adjustment guidelines to calculate their doses of insulin for each self-administration. However, they may follow their guidelines totally, partially, or not at all. The adherence of patients to these guidelines is very important and can affect their blood glucose levels.Methods for measuring patient adherence to drug therapy include self-reporting , patientDiabetes is a major worldwide problem; and non-adherence to antidiabetic therapy and its impacts are well-documented . ConcernWe present a method as well as a number of indicators that we developed for analyzing and monitoring of patients' adherence to their dose adjustment guidelines. We demonstrate our method in a group of type 1 diabetic patients who used an insulin dose adjustment guideline during supervised summer camps. We discuss the results and explain how our method and especially our indicators can be used in monitoring systems for real-time surveillance.We used a database of logbooks of patients attending summer camps organized by Aide aux Jeunes Diabétiques (AJD). The latter is a non-profit organization with a major role in diabetes education in France. Eligible patients were those aged between 13 and 17, whose parents accepted their participation in the study. Non-eligible patients were those who did not manage their diabetes on their own, and those with a coexisting disease.Twenty-eight patients  were included in the study. They used a guideline to calculate the doses of their insulin injections four times a day. All patients had the same diet and the same kind of physical activity during the camp. Their daily carbohydrate intake was constant and fixed in advance for each meal by AJD nutritionists. The camp personnel supervised patients to assure their good dietary compliance. Physicians registered patients' CBGs, self-administered insulin doses, physical activities, and any event on their health status in an online database (the database is accessible to patients and their physicians under authentication ). The FrWe used the official AJD guideline, taught to patients during summer camp. It consists of two pages of simple recommendations for the adjustment of insulin dose in a basal-bolus schema of insulin therapy including one injection of insulin lispro (or insulin aspart) before each meal, and one injection of insulin glargine before going to bed. This guideline was not specific for the kind of insulin, but for the schema of basal-bolus insulin therapy.The guideline made use of patient's CBGs, injected doses of insulin, any advent of hypo- or hyperglycemia, and physical activity in a rule based algorithm composed of conditions and actions. It did not take into account carbohydrate intake because it was considered constant for each meal  during the camp. As an example, to adjust the dose of insulin lispro before breakfast, the guideline proposed the patient to consider the CBG results obtained before lunch for two previous days, CBG measured at the moment of injection, and any physical activity over the next few hours. The guideline did not indicate the absolute dose of insulin. Instead, it provided instructions for the patients to adjust their own ongoing dose. The guideline is available as add-on material to this article.  Absolute agreement (AA): On-diagonal cell counts, which correspond to injections for which the patient's dose adjustment is the same as generated dose adjustment.b) Under-treatment (UT): Off-diagonal cell counts situated below the diagonal, which correspond to injections for which patient's dose adjustment is smaller than generated dose adjustment. Clinically, this indicator represents a hypoglycemia avoiding behavior.c) Over-treatment (OT): Off-diagonal cell counts situated above the diagonal, which correspond to injections for which patient's dose adjustment is greater than generated dose adjustment. Clinically, this indicator represents a hyperglycemia avoiding behavior.d) Relative agreement (RA): Off-diagonal cell counts adjacent to the diagonal, which correspond to adherent cases, but with some degree of tolerance.e) Extreme disagreement (ED): The outermost off-diagonal cell counts, which correspond to "potentially dangerous" cases. In our study, we defined this area as cell counts where patient dose adjustment was in an opposite direction (i.e. increase versus decrease) of generated dose adjustment.We used normal approximation of binomial distribution to construct confidence intervals (CI) for each indicator. We used also a weighted linear regression model  to deter2. Mean HbA1C was 7.8 (SD = 1.2)% at the beginning of the study. Mean CBG was 130 (SD = 70)mg/dl before breakfast, 170 (SD = 90)mg/dl before lunch, 180 (SD = 90)mg/dl before dinner, and 170 (SD = 90)mg/dl at bedtime.Patients mean age was 15 (SD = 1) years and their mean body mass index was 20.3 (SD = 2.8)kg/mMean injected daily doses of insulin lispro were 9.5 (SD = 4.4) units before breakfast, 9.4 (SD = 5.3) units before lunch, and 8.6 (SD = 4.1) units before dinner. Mean injected daily dose of insulin glargine was 20.7 (SD = 7.2) units at bedtime.Physicians made dose adjustments for patients on the first and the last two days of the camp. On all other days, patients adjusted themselves their doses of insulin under the supervision of physicians. Mean percentages of completion of the online database for dose adjustments before breakfast, lunch, dinner and at bedtime were respectively 92.6 (SD = 3.8), 90.4 (SD = 5.4), 86.7 (SD = 4.6) and 86.9 (SD = 4.8).We analyzed 1656 pairs of dose adjustments table . Two adjOverall rates of indicators for all patients and all insulin types were AA = 45% (CI = 2.3%), RA = 30%(CI = 2.1), ED = 2%, UT = 26%(CI = 2.3) and OT = 30%(CI = 2.1). As ED was too close to zero, its confidence interval was not calculated.Although over-treatment (OT) was more common than under-treatment (UT), there were less cell counts of extreme disagreement (ED) in OT area than in UT area (10 and 16 cases respectively). This suggests that extreme disagreement was more likely to be a result of under-treatment, i.e. hypoglycemia-avoiding behavior.We calculated indicators separately for different injections table . PatientWe calculated also the indicators for each patient table . The higWe analyzed the evolution of patients' therapeutic decisions over time by tracing the indicators of each day separately figure . The AA We fitted a weighted generalized linear model to examine the evolution of each indicator. The model fitted well (significance = 0.002) for the AA plus RA curve, but not for other indicators. It showed that the overall agreement progressed during the camp, and the rates of over- and under-treatments decreased smoothly. The extreme disagreement indicator, however, did not show a sensible change.We presented a method for measuring and analyzing patients' adherence to an insulin dose adjustment guideline. A computer system deployed the guideline, and generated dose adjustments for each insulin injection. The system compared these dose adjustments with patient-calculated dose adjustments, using contingency tables and related indicators. We traced the fluctuations of indicators over time, and showed their significance by use of a weighted linear regression model.By using indicators for measuring patients' adherence to guidelines, this study extends the method comparing insulin dose adjustments to computer-based insulin dose adjustment algorithms . The impWe used a locked database in retrospective "offline" settings, but the same method with no change is actually applicable for an online database to monitor patients' adherence in real-time.Three indicators, namely AA, OT, and UT, are based on statistically known concepts of on- and off-diagonal values of contingency tables. We designed two more indicators of RA and ED, which overlap with other indicators, for their clinical interest. The width of the zones defining these indicators on the contingency table depends on how precise the users of the method want to define their discrete categories. For example, if categories of dose adjustment were defined in two-unit intervals rather than one-unit intervals, the zone of relative agreement would be absorbed by that of absolute agreement .In our study, patient-calculated dose adjustments were in "absolute agreement" with those generated by the computer in less than half of injections (AA = 45%). We introduced the notion of "relative agreement" to detect those injections (RA = 30%) which are not strictly the same doses as calculated by the computer, but can be considered acceptable with a degree of tolerance of one unit. A similar strategy is used in the analysis of glucometer performances in form of the well-known Error Grid Analysis ,15.While measuring the impact of educational camps, it is especially interesting to know if there is an improvement in patients' adherence during the camp. In our study, this is confirmed by the crescendo curve of cumulative AA and RA indicators during the camp, which is demonstrated by a well-fitted linear model. However, for other indicators we could not fit a statistically significant model, which means that their predictive value for the studied population was limited.The detection of alarming situations is of paramount importance in monitoring of patient's adherence. The extreme disagreement (ED) indicator is designed to satisfy this need. Although its overall trend is shown to be stable by the regression line, its peaks may necessitate intervention in a real-time monitoring system figure .Two indicators, UT and OT, explain at least partly what patients do when they do not follow the guideline, and why. For example, the frequency of OT is particularly high for a patient table . This imA limitation of our study is that the significance of our indicators depends on the number of observations. Therefore, we need an initial period of a few days before being able to monitor a patient's behavior. Another limitation is the guideline itself. In fact, in 2006, AJD used the same guideline for both patients under insulin lispro and patients under insulin aspart. As our study was non-interventional, we used the guideline which was actually taught to the studied population during 2006. However, the study on this guideline showed some of its shortcomings, and helped developing a new version of the guideline the following years.Our proposed method and indicators are not specific to insulin self-administration. They can be applied in any other disease where patients decide for their dose of therapy, such as asthma or migraine headache.Our method allowed the analysis and monitoring of patients' adherence to an insulin adjustment guideline. The indicators were capable of providing quantitative data on the adherence of patients to the guideline not only for the studied population as a whole, but also for each individual patient. We are currently implementing these indicators in a telemedicine project, supported by the French National Authority for Health (FNAH), which aimed at monitoring young diabetic patients in real-time, and at alerting their non-adherent behavior to their physicians.CBG: capillary blood glucose; FNAH: French National Authority for Health; AJD: Aide aux Jeunes Diabétique; SD: Standard deviation; CI: Confidence interval; AA: Absolute agreement; RA: Relative agreement; OT: Over treatment; UT: Under treatment; ED: Extreme disagreement.The authors declare that they have no competing interests.MT carried out computer methods, participated in data collection and preparation, participated in the design of indicators and their calculation, and drafted the manuscript. CC carried out the follow-up of patients, obtained authorization from ethics committee, and participated in data collection, preparation and validation. GR verified the clinical value of findings and delimited indicators based on their clinical interest. MC organized patients' observations in camps, and participated in clinical validation of findings. AB carried out statistical methods, participated in the design of indicators, and verified statistical findings. AV conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Studied guidelines and system source code. This is an html folder containing the studied guidelines in English and French, the de-identified patient database and the source code of the computer system. The file may be downloaded and unzipped in a folder. All the content of the folder can be accessed by double-clicking on "index.htm" file in the folder root.Click here for file


Most studies on Health-related Quality of Life (HRQOL) in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL) patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL.After cultural linguistic validation, a cross-sectional study of HRQOL was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life Inventory™ (PedsQL™) 4.0 Generic Core Scale and the Pediatric Quality of Life Inventory™ (PedsQL™) 3.0 Cancer Module.Ninety-eight guardians and 55 patients participated. The internal consistency of both scales ranged from 0.57 to 0.92. HRQOL of Indonesian patients was comparable with those in developed countries. There were moderate to good correlations between self-reports and proxy-reports, however guardians tended to report worse HRQOL than patients. Children of the 2–5 year-group significantly had more problems in procedural anxiety, treatment anxiety and communication subscales than in older groups (p < 0.05). In the non-intensive phase HRQOL was significantly better than in the intensive phase, both in patient self-reports and proxy-reports.Younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided to children and their parents to facilitate their coping with disease and its treatment. The survival rate of acute lymphoblastic leukaemia (ALL), the most common malignancy in children, has improved in recent years to a 5-year survival rate of about 80% ,2, althoHRQOL is defined as a multidimensional construct composed of the patients' perceptions of the impact of disease and treatment on his or her functioning in a variety of aspects of life, including physical, psychological and social health domains ,9. PediaSome studies found that there was correlation between gender and socioeconomic status (SES) and health status influence HRQOL ,17. Manyst, 2nd, and 3rd class) and a policlinic .Indonesia is a multi-island state, and has a population of approximately 220 million of whom 37% are children under 15 years. A childhood leukemia incidence of 2.5 to 4.0 new cases per 100 000 children leads to an estimated 2000 to 3200 new childhood ALL cases each year [After cultural linguistic validation, a cross-sectional study was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life Inventory™ (PedsQL™) 4.0 Generic Core Scale and the Pediatric Quality of Life Inventory™ (PedsQL™) 3.0 Cancer Module. The cultural linguistic validation process consists of 3 steps: forward translation, backward translation, and patient testing. In the first step, the instruments were translated from English version to Bahasa Indonesia version, and it was done independently by two local professional translators, native Indonesia speakers, and bilingual in English language. The second step, the Bahasa Indonesia version was translated back to English version and it was done independently by two local professional translators, native English speakers, and bilingual in Bahasa Indonesia language. In this step a comparison between the backward version with the original version was assessed in order to detect any misunderstandings, mistranslations or inaccuracies in the intermediary forward version of the questionnaire. Finally, the translated questionnaire was tested in 5 cancer families, both in children and their guardians, to determine whether the translation  is acceptable, whether it is understood in the way it is supposed to be, and whether the language used is simple and appropriate. All PedsQL™ translations were conducted in close ongoing collaboration with Mapi Research Institute in Lyon, France and with Dr. James W. Varni.Participants were childhood ALL patients who were hospitalized or visited the policlinic at Dr Sardjito Hospital, Yogyakarta, Indonesia, from October 2006 until January 2008. Eligible patients were children of 2–16 years at time of diagnosis. Patients with severe conditions who were not able to answer the questionnaire were excluded. During this period 2 ALL dexametasone-based protocols were used: Wijaya Kusuma ALL protocol and Indonesia ALL protocol. According to both protocols there are 2 risk groups: standard risk (SR) and high risk (HR). Both protocols consist of an induction, consolidation, re-induction (only for HR) and maintenance phase. We classified the phase as either intensive  or non-intensive (maintenance). Interviews of eligible patients and their guardians, who were interviewed separately, were performed individually by a trained psychologist. It took 10–20 minutes for guardians and 20–45 minutes for patients to complete the questionnaire. Demographic data regarding information about age, relationship of respondent to child, number of children in the family, parental educational status, and socio-economic status were collected from guardians. Parental educational status was categorized into low educational status  and high educational status . We classified SES as either poor or prosperous. This classification was based on 2 determinants: monthly income level of parents and assigned hospital class during the diagnostic process. Both determinants are obtained routinely during admission to the clinic and recorded in the medical records. The threshold per month income for poor versus prosperous families was set at 1.000.000 Indonesian Rupiah (about 100 US dollar). Patients attending VIP or first class wards and VIP policlinic were classified as prosperous. In case there is discordance between family income and hospitalization class or data of family income is not available, we used hospitalization class as SES determinant. Medical data regarding diagnosis and treatment status were obtained from the patients' MR. The study was approved by the Medical Ethics Committees of Faculty medicine, Gadjah Mada University. Informed consents were also obtained from the guardians.The PedsQL™ 4.0 Generic Core Scale  is a multidimensional instrument developed by Varni et al . It consThe PedsQL™ 3.0 Cancer Module (Cancer Module) is a multidimensional instrument developed by Varni et al. to assess the impact of disease and treatment on the HRQOL of pediatric cancer patients . It consThe scale has five Likert response options: never, almost never, sometimes, often and almost always. To simplify the interpretation, all Likert scales were converted to 0–100. The higher scores indicate a higher HRQOL. For the versions adapted to children between the ages of 5 and 7 years, there are only three response options: never, sometimes and almost always . For this age, a Face Scale was used, comprising of 3 pictures of facial expressions varying from a smiling face to a very sad face to indicate no problem/difficulty/pain to a lot of problems/difficulty/pain.The internal consistency of the Generic Scales and the Cancer Scale were measured by Cronbach's Alpha Coefficient. Values ≥ 0.70 were considered acceptable for comparisons between groups . The corDuring October 2006 – January 2008, 110 ALL patients were hospitalized or visited the pediatric department of Dr. Sardjito Hospital. Ninety-eight patients were recruited according to the inclusion and exclusion criteria. There were no significant differences between the studied group and those who did not participate with regard to demographic characteristics. All guardians completed the proxy-reports questionnaire. Fifty-five patients participated in patient self-report, 3 (10%) patients of 5–7 year-old age group did not wish to answer the questionnaire. There was no significant difference between proxy-reports and self-reports with regard to age, gender, parental educational status, SES, ALL risk stratification, and phase of treatment. The average age of all patients was 6.6 years (SD = 3.7), median 6 years, range 2–16 years. Most respondents of proxy reports were mothers , and most families  belonged to low SES , but other subscales only showed a weak-moderate correlation (ICC 0.31–0.60). Guardians tended to report lower HRQOL than did patients in Cancer Scale. In both self report and proxy report, psychosocial health subscale was better than physical health subscale table .Gender, position of the child in the family, SES, parental educational status, and risk stratification did not correlate to any scales of HRQOL table . HoweverAlthough recent survival rates of childhood acute lymphoblastic leukemia (ALL) in developed countries are about 80%, the survival rates in developing countries are often less than 35%. In our previous study the overall even-free survival rate was only 20% . One migThere was no significant difference on HRQOL between different SES and parent educational status. Other study found the similar results . HoweverIn both self-reports and proxy-reports, the psychosocial health subscale was better than the physical health subscale. This result was similar to other studies assessing HRQOL in ALL patients on treatment ,25. In cAs can be expected, HRQOL scores in the non-intensive phase were generally significantly better than in the intensive-phase, in both self-reports and proxy-reports. Significant differences were found in the physical health, pain, procedural anxiety and communication subscales. These results are similar to earlier studies ,20,25. IIn the non-intensive phase, both patients and their guardians perceived that children had lower scores, more problems, in worry and emotional subscale. It is not surprising that patients still worry about side-effects of the chemotherapy and curability of ALL since many patients in our hospital suffer from severe side-effects or die during the course of treatment. This concern about side-effects and curability may be a reason for non-compliance. Therefore it is important that health care providers improve their quality of care to reduce side-effects and improve survival rate.We, like others ,17,27. fIn summary, younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided for both children and their guardians to facilitate their coping with the disease and its treatment.ALL: acute lymphoblastic leukemia; HRQOL: health-related quality of life; PedsQL™: the Pediatric Quality of Life Inventory™.The authors declare that they have no competing interests.All authors collaborated in the study design; MNS collected the data; MNS and CG conducted the analysis; MNS, SM, CG, ST, AV drafted the paper; and all authors reviewed and approved the manuscript.Comparison means score of HRQOL (cancer module) between different demographic and medical characteristics: proxy report.Click here for file


P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan–Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test  Despite pivotal developments in endocrine therapy and chemotherapy, resistance to therapy remains a key limitation in the management of invasive breast cancer. A fundamental difficulty in the understanding, prevention, and treatment of breast cancer is clinical heterogeneity between tumours. This is commonly manifested as variable responses to specific therapeutic regimens. Numerous studies indicate that this clinical heterogeneity reflects underlying molecular heterogeneity. Tumour hypoxia is a micro-environmental factor related to poor response to radiation and chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis  sections from each case were screened by a pathologist and appropriate representative areas of tumour highlighted for sampling. Tissue cores for the construction of tissue microarrays (TMAs) were taken with a 3-mm skin punch biopsy needle  from the paraffin blocks that were used for histological diagnosis. The tissue cores were inserted in the holes of the rectangular carrier made of liver tissue, punched out by a 4-mm punch biopsy needle . The carrier facilitated the smooth cutting of sections with minimal artefacts in transition from paraffin to tissue.Each carrier had a grid of 4 × 5 holes and, in addition to the breast tumour tissue samples, contained one core of normal breast tissue as a control. Four cores per sample, from multiple areas of the same tumour, were included in the TMA and embedded in different blocks at different positions on the grid for redundancy. After core insertion, tissue was re-embedded in paraffin. A small number of cores were damaged during TMA construction or subsequent methods and were labelled as noninformative. On an average, 83.4% of the cores, or 3.3 cores per specimen, were informative and were used in the analysis.  and heated for 1 h at 60°C. After deparaffinising and rehydration, sections were treated in 0.3% H2O2 in water to block endogenous peroxidase activity. Antigen retrieval was performed using the ALTER technique as previously described  and once by a pathologist (RG), both of whom were blinded to any other data. The whole of each section was subjectively assessed under light microscopy. For assessment of the level of CA IX expression, individual tumours were scored according to the level of staining in tumour cells. Staining of the biliary epithelial cells within surrounding liver (used to support the breast cores) served as the internal positive control (unpublished data). There was one score for the strength of staining  and one score for distribution pattern within the tumour stained . Sections where intra-observer or inter-observer error occurred for either of the scores were reviewed again by a pathologist (RG) and assigned a score that dictated which of the two original scores was recorded. In the event of all three pairs of scores differing, a consensus score was agreed upon after examination by both observers (SAH and RG) at a multiheaded microscope. Tumours were categorised into five patterns of expression of CA IX: tumour negative, weak diffuse (WD), weak focal (WF), strong diffuse (SD), or strong focal (SF). Expression of CA IX, whether strong or weak and focal or diffuse was grouped as positive.χ2 and Fischer's exact tests for the categorical measures and t-tests for the numerical measures. Survival times were calculated as the date of primary tumour diagnosis to date of death, or date of censor, if alive. Survival curves were constructed using the method of Correlations between CA IX (positive or negative) and known prognostic variables of tumour size (numeric), tumour grade , axillary lymph node status (positive or negative), side of tumour (left or right), surgery type (mastectomy or WLE+ ALNC), vascular invasion (present or absent), ER status (positive or negative), DCIS grade , and the Nottingham Prognostic Index , DCIS grade (P=0.89), axillary lymph node status (P=0.38), and ER status (P=0.11), side of tumour (0.50), surgery type (P=0.13), vascular invasion (P=0.59), tumour grade (0.40), and Nottingham Prognostic Index (P=0.39).There was no evidence that CA IX expression was associated with known prognostic variables, specifically tumour size (P=0.01). In a Cox regression analysis, based on the 133 patients with complete data, even after adjusting for the NPI, CA IX remained significantly associated with survival (P=0.03). In fact, when adjusting individually for any of the prognostic variables in P=0.049) and CA IX marker status . The remaining variables of tumour size, tumour grade, nodal status, surgery type, ER status, and NPI did not reach the level of statistical significance required for inclusion in the model.At the time of analysis, 28 of the 144 patients had died . Median follow-up for the alive patients was 48 months (range 5–71 months), with 96% having at least 2 years follow-up. In a univariate analysis, the data showed some evidence for vascular invasion, ER status, Nottingham Prognostic Index (NPI), and tumour grade to be prognostic for survival, although not all at a statistically significant level, possibly owing to the relatively small size of the study . SurvivaRecent studies have demonstrated that many human tumours are hypoxic. This is likely to be due to compromised micro-circulation within a tumour. The clinical importance of tumour hypoxia is its association with a more aggressive malignant phenotype, increased risk of metastasis, and resistance to chemo- and radiotherapy . This may be due, in part, to heterogeneity in CA IX staining both within and between individual tumours, which might lead to inaccuracy in estimating the number of positive and negative tumours. Additionally, this may be related to differences in technique and interpretation in nonstandardised immunohistochemistry assays. It was interesting to note that when adjusted individually for any of the prognostic variables, vascular invasion and CA IX expression always remained significantly associated with survival and the HR from our multivariate analysis was comparable to that found by Chia Hypoxia is reported to be an adverse prognostic factor in most human tumours. This study demonstrates that 26% of breast cancers are positive for CA IX expression. This information may have prognostic value in that CA IX expression is a predictor of poorer survival independently of other recognised prognostic factors. This information may, therefore, facilitate a more refined selection of patients for adjuvant treatment. By adding to established prognostic factors, CA IX expression may contribute to the identification of patients at greater risk of relapse who should be offered adjuvant treatment while sparing those whose prognosis is already good.At the time of diagnosis for the patients in this series, Her-2 testing was not routinely performed. Thus, correlations between CA IX expression and Her-2 could not be made. Because of the prognostic importance of Her-2, this question must be addressed in future prospective studies in patients with known Her-2 status.Furthermore, as hypoxia is related to resistance to chemotherapy and radiotherapy, CA IX expression may serve as a predictive factor to guide the selection of the most appropriate adjuvant treatment modality. Moreover, as hypoxia as a cause of treatment resistance can be effectively overcome by a variety of strategies, including high-oxygen-content gas breathing, blood transfusion, haemoglobin–oxygen affinity modifiers, and nicotinamide, the incorporation of these could be further investigated in patients with breast cancer.Finally, the expression of CA IX in a number of breast tumours examined in this study, compared to the absence of CA IX in normal breast tissue, indicates that hypoxia and hypoxia-related gene expression may present a useful target for novel targeted therapies, for example drugs or gene therapy vectors that are specifically activated under hypoxic conditions. This study provides a rationale basis for the further study of these approaches in breast cancer. Randomised studies with translational end points are required to further elucidate the prognostic and predictive value of CA IX. Prospective study within the context of an adjuvant chemotherapy trial is underway to investigate and explore this correlation in clinical trial setting.


The perception of entrapment can emerge when defeated individuals want to escape but are incapable. Studies have shown relationships of entrapment to depression, and suicidal tendencies. The aim of this study was a psychometric evaluation and validation of the Entrapment Scale in German (ES-D). 540 normal subjects completed the ES-D along with other measures of depressive symptoms, hopelessness, and distress. Good reliability and validity of the ES-D was demonstrated. Further, whereas entrapment originally has been regarded as a two-dimensional construct, our analyses supported a single-factor model. Entrapment explained variance in depressive symptoms beyond that explained by stress and hopelessness supporting the relevance of the construct for depression research. These findings are discussed with regard to their theoretical implications as well as to the future use of the entrapment scale in clinical research and practice.The construct of  Assuming a certain degree of adaptivity of behavior and emotion, evolutionary theorists have suggested various functions of moodiness and depression. Whereas adaptive mechanisms may become functionally maladaptive , 2, therarrested flight. For example, in lizards, being defeated but able to escape has proven to be less problematic than being defeated and being trapped. Those who are in caged conditions, where escape is impossible, are at risk of depression and even death  = 7.34, P < .01, d = .63), felt more entrapped , and more stressed  than participants of the PP-sample. The two samples did not differ regarding hopelessness . Further, the PP and the OL sample were split according to the cutoff of the CES-D which is considered indicative of dividing subjects with clinically relevant depressive episodes from healthy subjects  = 9.43, P < .05, ϕC = .16). At baseline, (t1) subjects taking part at the retest 3 months later (t2) did not differ from persons not taking part in the retest with respect to depressiveness, perceived stress, or hopelessness, but differed regarding entrapment .As stated above, the retest-sample (RT) was a subsample of the OL-sample. The 100 retested persons were significantly older than the subjects not taking part in the retest assessment (δ = 0). Data was suitable for an EFA according to Bartlett's test  and Kaiser's measure of sampling adequacy , so that the items could be considered apt for factor analyses. The Kaiser-Meyer-Olkin measure (KMO) also indicated that sample size was adequate in both samples . A principal-axis EFA was conducted for both samples using the covariance matrix and oblimin rotation (N = 170), the single-factor solution explained 60.72 % of the variance. For the online sample (N = 370), the single-factor solution explained 58.52% of the variance. In both cases, all items correlated significantly (P < .01) with the main factor .Following the study of Taylor et al. , the algα of the ES-D was .95 for both the PP and the OL samples. These values were similar to those found in studies using the original ES. Split-half reliability of the ES-D was r = .92 (Spearman-Brown) in both samples. Cronbach's  To examine the construct validity of the ES-D, entrapment scores were correlated with total depression scores, with hopelessness scores, and with perceived stress scores in both samples see . Entrapmf2) for change in ΔR2 due to the addition of entrapment were small in both samples . Incremental validity of the ES was operationalized by a significant increment in the explained variance in the prediction of depressive symptoms. The assumptions for multiple linear regressions, including measures for collinearity, were not violated by our data, and no multivariate outliers or influential cases were identified. n = 100). As expected, in the RT-sample mean values for entrapment, depressive symptoms, perceived stress, and hopelessness remained unchanged from t1 to t2 . In terms of stability, moderate correlations between values at t1 and t2 were found for entrapment , perceived stress , and depressive symptoms  whereas hopelessness showed a comparably higher retest correlation . When comparing the correlations [ The sensitivity to change of the ES-D was assessed by analyzing the data of a retest (RT) after 3 months . Furthermore, the state of entrapment seems to be more stable than perceived stress, which may be influenced to a greater extent by external factors. Given the confirmed reliability and validity of the ES-D in this study, we therefore cautiously conclude that entrapment lies between hopelessness and perceived stress regarding stability.The state conceptualization of entrapment implies that the perception of entrapment may change over time. Therefore, we did not expect retest correlations as high as retest correlations for more trait-like constructs like hopelessness . Since tWhereas the high correlation between entrapment and depressive symptoms in this study may be interpreted as evidence of conceptual equivalence, an examination of the item wordings of two scales clearly suggest that these questionnaires assess distinct constructs. However, the causal direction of this bivariate relation is not clear. Theoretically, both directions are plausible. Entrapment may be a cause or a consequence of depressive symptoms, or even both. Unfortunately, studies examining the temporal precedence so far have yielded equivocal results and have methodological shortcomings  in order to answer this question conclusively , 26. It The present study has notable limitations. This study used two nonclinical samples. It was not systematically assessed by clinical interviews, whether any of the participants were suffering from clinically relevant depressive episodes. However, a cutoff that is considered indicative of clinically relevant depression was applied . Future The assumption that individuals feeling trapped in a situation are still highly motivated to change their situation suggests possible implications for research and practice. First, further research needs to identify groups of people who are especially prone to entrapment . Second, further research has to investigate to what extent the feeling of being trapped can be changed by psychological interventions. If entrapment can be changed, clinicians may set out to find individual sources of entrapment for each patient. Depending on whether he or she deems these potential sources as changeable or stable, challenging and/or accepting them may be the appropriate intervention strategies to help the patient overcome the feeling of being trapped. Such “entrapment-focused interventions” could be integrated in existing programs for the psychotherapy of depression.


The aim of this study was to evaluate the acute effects of different inspiratory loads and different interfaces on the breathing pattern and activity of the respiratory muscles.Twenty healthy adults were recruited and assigned to two groups  by way of randomized crossover allocation. Subjects were evaluated during quiet breathing, breathing against inspiratory load, and recovery. The measurements were repeated using two different interfaces . Chest wall volumes and respiratory muscle activity were assessed with optoelectronic plethysmography and surface electromyography, respectively.p < 0.04), inspiratory time (p < 0.02), minute ventilation (p < 0.04), tidal volume (p < 0.01), end-inspiratory volume (p < 0.04), end-expiratory volume (p < 0.03), and in the activity of the scalene, sternocleiomastoid, and parasternal portion of the intercostal muscles  when compared to quiet breathing, regardless of the load level or the interface applied. Inspiratory load application yielded significant differences between using nasal and oral interfaces with an increase in the tidal volume (p < 0.01), end-inspiratory volume (p < 0.01), and electrical activity of the scalene and sternocleiomastoid muscles (p < 0.01) seen with using the nasal interface.During the application of inspiratory load, significant changes were observed in the respiratory rate (The addition of an inspiratory load has a significant effect on the breathing pattern and respiratory muscle electrical activity, and the effects are greater when the nasal interface is applied. The application of an inspiratory load is a method used for inspiratory muscle training (IMT) ; it helpIn inspiratory flow resistance devices, subjects perform inspirations through an orifice of variable diameter; the smaller the orifice diameter, the greater the resistive inspiratory load. However, these devices depend on the inspiratory flow generated by the subject. The new generation of electronic devices have overcome this limitation, in that, they are based on an electronically controlled variable flow resistive load. It has been reported that its use produces higher training loads and better inspiratory function when compared to pressure threshold devices . HoweverThe act of breathing is a vital biological process that, in normal conditions, occurs through the nose, for the purpose of filtering, humidifying, and heating the inspired air. Warmed, humidified air minimizes airway constriction and the resultant increased airway resistance. In addition, it improves upper airway mucociliary function, which augments the elimination of secretions. Despite this, the respiratory resistance devices available in the market only use mouthpieces . The use of a nasal interface, for training inspiratory muscles, could be more favorable physiologically and more viable for individuals who are unable to hold a mouthpiece, such as patients with facial trauma or neurological problems that cause weakness of the facial muscles. Therefore, considering the possible benefits of nasal breathing on the respiratory system, we hypothesized that the use of a nasal interface will improve breathing pattern and the variation of chest wall volumes, as well as the electrical activity of the respiratory muscles.2. We excluded individuals that failed to perform the tests/protocol, as well as those who presented irregularities during data analysis or voluntarily requested their removal from the study.This research was carried out at the PneumoCardioVascular Lab, in the Federal University of Rio Grande do Norte/Brazilian Company of Hospital Services (UFRN/EBSERH) in the city of Natal/RN. We included, in the study, young adults belonging to the male and female sexes, presenting normal values of pulmonary function, with ages ranging from 18 to 30 years and with Body Mass Indexes (BMIs) between 18 and 29.9 kg/mThis study was approved by the Hospital Research Ethics Committee (number 428.987). The participants signed the consent form, which was drafted according to the tenets of the Helsinki declaration related to research on human beings, including special attention to confidentiality, respect for the human person, beneficence, autonomy, and non-maleficence.® spirometer . The evaluations were performed according to the criteria of acceptability and reproducibility of the American Thoracic Society/European Respiratory Society (ATS/ERS) (Spirometry was performed using the KoKo DigiDoserATS/ERS)  and the ATS/ERS) .Respiratory muscle strength was determined by measuring maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and sniff nasal inspiratory pressure (SNIP) using a digital manovacuometer . The evaluations were performed according to Cp), the abdominal rib cage (RCa), and the abdomen (Ab) was performed by Optoelectronic Plethysmography , in which volumes were obtained following an experimental model according to the Gauss theorem  and its compartments: the pulmonary rib cage , tidal volume in pulmonary rib cage , tidal volume in abdominal rib cage , and tidal volume in abdomen ]; end-inspiratory volumes ; end-expiratory volumes ; respiratory rate (RR); inspiratory time (TI); expiratory time (TE); inspiratory flow (FlowI); expiratory flow (FlowE); minute volume (MV); and total time of respiratory cycle (TTOT).From the OEP data, the following variables were analyzed for the CW and its compartments: tidal volume , which consists of an orofacial mask associated with the resistive valve, was used. During its use, participants were asked to breath exclusively through the nose.A routine was developed in MatLab  to synchronize sEMG and OEP data. The resulting file was used to analyze the breathing pattern data, breath-to-breath data, on Diamov . Furthermore, the file was also used to select the length of time and calculate RMS on MR 3.2 software.The digital filters applied to EMG signals were electrocardiogram filter for cardiac electric signal removal, rectification, and smoothing filter for the elimination of non-reproducible signals (50 ms window).20% with an oral interface ( = 0.36), MIP20% with a nasal interface . A sample size ranging between 15 to 21 subjects for each group with a mean of 19 subjects was estimated using the following: an alpha error of 0.05 with bilateral distribution, and a test power of 80%, an effect size resulting from the ANOVA test described through the partial eta squared  for Windows was used. The power (β) and effect size (ES) were estimated and are detailed in the results section of this study. For all statistical analyses, a level of significance, p < 0.05 with bilateral distribution was adopted.Data normality was verified using the Shapiro–Wilk test. The Friedman test was used to analyze the steps of spontaneous quiet breathing, breathing against inspiratory load, and recovery, and in the case of a significant difference, Dunn’s The sample size calculation, β, and ES of the study were calculated using GPower software version 3.1.9.2 .Twenty-nine subjects were screened, of which three did not meet the inclusion criteria. Six subjects were excluded due to low quality of their electromyography signals and/or OEP volumes, resulting in a final sample of 20 subjects. The sample description and characterization referring to baseline anthropometric and pulmonary function data are shown in T,CW, VT,RCp, VT,RCa, and VT,Ab), while operational volume variations  are shown in T,CW were observed during the Load step compared with the QB and Rec steps (p < 0.01). VT,CW and compartmental volumes were higher when using the nasal interface (p < 0.05) compared with the volumes observed when the oral interface was used. The MIP40% group presented an increase of 0.16 and 0.15 L with the oral and nasal interfaces, respectively, than the MIP20% group. However, these values were not statistically significant.Regardless of the imposed load, significant increases in VCW  and a reduction in EEVCW  resulted.Regarding the variations of operational volumes during breathing against inspiratory load, an increase in EIVRCp  and a mean increase of 0.22 L in EIVRCa , when compared to the QB and Rec steps, resulting in a greater EIVCW. There was no significant variation in the abdomen. The EEVCW reduction, in response to an increased ventilatory demand, was mostly related to the volume generated in the abdominal compartment (EEVAb) . The abdominal compartment had a mean volume decrease of 0.16 L, whereas the rib cage maintained a constant volume.During the Load step, there was a mean increase of 0.38 L in EIVCW was higher with loads imposed via the nasal airway (MIP20% and MIP40%: p < 0.01), with no differences in relation to EEVCW.Comparing the Load step when using the nasal and oral interfaces, EIVTOT, TI, MV, FlowI, FlowE, and RR varied during breathing against both inspiratory loads (MIP20% and MIP40%) compared to QB, with only TTOT not presenting significant variations with the MIP40% load. TE did not vary in any of the conditions. The comparison between different interfaces and load intensities did not show any statistically significant difference.As shown in p < 0.01) in relation to the QB and Rec steps. The comparison between interfaces revealed significantly higher RMS values of the nasal interface for SCM  and SCL (p < 0.01). sEMG signals were higher in MIP40% than MIP20% for SCM (p < 0.01), SCL (p < 0.01), and IC (p < 0.01). The RA muscle did not show any significant variations in its activity when different loads or interfaces were used.Surface electromyography signals normalized by expressing RMS as percentage of resting conditions are shown in Cp and RCa compartments, and the latter by its decrease in the abdomen compartment; (2) these changes were followed by increased electrical activity of the SCL, SCM and IC muscles; (3) these effects were more evident when using the nasal interface.We studied the acute effects of adding variable flow inspiratory loads using nasal and oral interfaces on the respiratory pattern variations and respiratory muscle activation. The addition of inspiratory loads resulted in: (1) increased tidal volume due to changes in the end-inspiratory volume and end-expiratory volume, the former occurring due to its increase in the R2O L–1 s–1 at 0.5 L s–1) and is relatively fixed, regulated by both the alar muscles and the nasal mucosa. In contrast, the oral airway presents a lower resistance (RO = 0.51 cmH2O L–1 s–1 at 0.5 L s–1); however, there is a high variability in resistance in response to mouth opening  promoted greater lung volume generation and inspiratory muscle activation when compared to the oral interface . There are mechanical differences between the nasal and oral airways, depending on the region. The nasal airway has a higher resistance  and compartmental  volumes was similar in both groups and although these volumes presented higher values in MIP40% the change was not significant. The increase in chest wall . By reducing the EEV, the abdomen compartment also contributes to the increase of the VT,CW. These results were previously described by CW and decreased EEVCW in response to ventilation increased. These authors observed a reduction of 0.98 L in EEVCW during exercise and identified the abdomen as the volume generator, which corroborates our study. Rcp and EIVRca, which are in agreement with our results. Both authors observed that in response to an increased ventilatory demand due to exercise, there is an increase in VT of the rib cage associated with an increase in EIV, whereas the increase in VT,Ab results only from a reduced EEV. They also suggested the importance of this arrangement in respiratory mechanics physiology.The tidal volume is represented by the differences between end-inspiratory volume and end-expiratory volume generation . AlteratAb reduction associated with the constant volume in the rib cage (RCp and RCa) is a mechanism that supports the diaphragm muscle action. This increases the diaphragm pre-inspiratory length and prevents its excessive shortening during inspiration. In contrast, EIV increase associated with the rib cage volume, maintaining constant volume in the abdomen, favors the shortening of the chest wall inspiratory muscles during inspiration, preventing their excessive pre-inspiratory stretching  than the SCM (2.0 l–1). The secondary inspiratory function of the SCM, justifies its delayed recruitment. These values are representative of a mechanical advantage and were calculated by an indirect approach, based on the Maxwell reciprocity theorem. This theorem, when applied to the respiratory system, predicts that the potential change in the airway pressure produced by a particular muscle contracting alone against a closed airway is related to the mass of the muscle, the maximal active muscle tension per unit cross-sectional area, and the fractional change in muscle length per unit volume increase of the relaxed chest wall (Physiologically, the SCL and IC muscles have a primary inspiratory action and greater mechanical advantage (3.4 and 2.2 lest wall . Anotherest wall . Even thest wall . The facIn summary, responding to inspiratory loads, the IC and SCL are initially recruited, but only the SCL responds by increasing its activation intensity according to the load. At loads greater than 20% of MIP, the SCM is recruited and has a similar intensity to the SCL due to its larger size. The SCM also increases its activity to match the load.We did not find variations in the RA muscle activity in any of the comparisons made. We did not analyze the activity of the external oblique, transverse abdominus, and internal oblique muscles. They are more sensitive to detecting abdominal muscle activity. This is a limitation to the present study. We used sEMG, which was not very effective in measuring the RA muscle activity, because of the thicker adipose layer covering. Another limitation to this study is the fact that the acute effects were assessed only for a limited period, which was necessary for the integrated analysis of the OEP and sEMG systems. However, the study presented favorable evidence on the use of inspiratory flow load and its application to upper airways, such as a better breathing pattern and greater muscle activation. An increase in lung volume mobilization in response the imposed load favorable to causing restrictive disorders was observed, without an increase in the end-expiratory volume and therefore, allowing its use also in obstructive disorders. In addition, we believe the nasal interface could be used as an alternative for treating patients with muscle weakness or facial deformities when it is not possible to use mouthpieces. Longitudinal studies must be performed in order to identify the long-term effects of inspiratory load application on ventilation and respiratory muscle strength.The results of our study indicate that applying inspiratory loads with a nasal interface is more effective in eliciting an increase on the inspiratory muscle activity, the chest wall and the compartmental volumes. As a perspective for future studies, we suggest evaluating the effects of IMT with a focus on the upper airways, in order to observe its repercussions on lung function.We declare that the above mentioned manuscript was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte under protocol 1.251.451/2015, according to the Declaration of Helsinki of 1975.JdF: literature search, data collection, study design, analysis of data, and manuscript preparation. KB: analysis of data and manuscript preparation. VR: review of manuscript. GF: study design and review of manuscript. AA: literature search and review of manuscript.AA is a co-inventor of the optoelectronic plethysmography whose patent rights are held by his institution, the Politecnico di Milano. The remaining 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.


Background: The incidence of sedation-related adverse events, inclusive of both adults and children, administered by multiple specialty providers from different countries and venues, using standardized definitions, has never been reported on an international level. We are reporting the outcome data of the adverse event sedation reporting tool as an important step toward a more complete risk assessment of sedation-related morbidity, mortality, and etiology. The analysis of the AE sedation reporting data include descriptive measures to evaluate the characteristics of the provider, the patient, sedations performed, adverse events, interventions, and outcomes. The primary outcome was the rate and nature of adverse events. Between 12/14/2010 and 12/11/2018 there were 7952 sedations, from an estimated total of 164,114 sedations administered, of which 622 were reported as adverse events. The mean age of the entire patient population is 33.0 years (0.02–98.7). The providers represented 39 countries across six continents. Oxygen desaturation (75%–90%) for <60 s is the most prevalent adverse event with a rate of 7.8 per 10,000, followed by airway obstruction at a rate of 5.42 per 10,000. Apnea occurred at a rate of 4.75 per 10,000. Significant predictors of adverse events are ≥ ASA score III (p = 0.0003), procedure time , and non-hospital location (p < 0.0001). The AE sedation reporting tool has demonstrated that the majority of adverse events in children and adults who receive procedural sedation from multi-specialists internationally required minor interventions and had outcomes of minor risk. Procedural sedation, for both adults and children, encompasses a wide range of patients, procedures, venues, and specialty providers. The collecting of sedation outcomes can be challenging, as it requires vigilant need to identify, report, and document multiple identifiers. To date, there is a paucity of large scale reports of sedation outcome. The large scale studies in the literature are generally limited to a single patient population , sedation provider , sedation technique , venue , procedure , and country  ,19,20,21www.AESedationReporting.com) and published as a manuscript in 2012, as the first tool in existence which would standardize the reporting and tracking of all sedation-related adverse events [www.AESedationReporting.com website by providers worldwide. This database for sedation-outcome reporting supports the collection and sharing of data. The goal of this manuscript is to evaluate the adverse event sedation reporting data in order to determine whether there are any risk factors or predictors of adverse events. This is the first report of adverse event sedation data collected using this AE reporting tool, with international contributions of multi-specialists providing care of adult and pediatric populations. This report is an important first step toward a more complete risk assessment of sedation-related morbidity, mortality, and etiology that could direct efforts to further future safe sedation.This report is the first to present the incidence of adverse events, collectively for both adults and children, for sedation delivered by multiple specialty providers performing a wide range of procedures in different countries and venues. The adverse event (AE) sedation reporting tool was published online in 2011  comprised of physicians from 10 specialties to 11 countries  presented the adverse event sedation reporting tool as a consensus document intended to standardize the definitions and terminology of sedation related adverse events . The IntThe AE sedation reporting tool requires individual registration prior to utilization, to collect specifics that include the sedation provider’s first and last name, email address, specialty, place and type of practice, educational background, city and country of current practice, phone number and predominant patient population—adult, pediatric, or both. Every time that the registrant logs onto the website to input data, he/she is required to provide an estimate (or update) of the total number of sedations personally performed in a year. The tool consists of contiguous screens, through which the user progresses, each of which requires full completion prior to moving on to the next . The purpose is to identify the occurrence (or non-occurrence) of an adverse event, the urgency of the procedural sedation (emergent versus non-emergent), describe the adverse event using one or more objective, clearly defined descriptors and then in the event an intervention was needed, define what was performed . When enOutcome measures are categorized as minimal (no adverse outcome), moderate , or sentinel . There may be occasions in which there may be more than one outcome, each with different severity . In this circumstance, the overall severity of the adverse event is assigned a rating  based on the most severe outcome.The analysis of the AE sedation reporting data included descriptive measures to evaluate the characteristics of the provider, the patients, sedations performed, interventions, outcomes, and their adverse events. The primary outcome was the rate of adverse events. The secondary outcome was to determine predictor variables of adverse events from sedation.p-value less than 0.05 were considered statistically significant. All statistical analysis was performed using SAS . Incidence rates of adverse events were calculated using the number of events and the estimated number of sedations per year by the provider. Their cumulative sum will be representative of the entire sample of sedation related adverse and non-adverse events. A stratified random re-sampling simulation of non-adverse events based on the distribution of non-adverse events reported was performed to enable further analyses. A multivariate logistic regression model was developed to identify predictors of adverse events. Predictor variables were chosen on the basis of the data (patient and provider) collected: American Society Anesthesiologist (ASA) score, age groupings, gender, time of procedure, and location of procedure. Odds ratios (ORs) and 95% confidence intervals (CIs) without adjustment for multiple comparisons were considered. The data for this study was collected from 12/14/2010 to 12/11/2018 and included 7952 sedation entries, of an estimated 164,114 total sedations performed over this time period. The premise is that from the estimated number of sedations performed each year, there were no adverse events that occurred in the remaining 156,162 cases that did not have data recorded (other than the 622 that were reported in the 7952 cases entered). All sedation entries had complete data points, as every screen must be completed in order for the user to continue data entry in the tool and save the data. The patient data presented in The providers (users of the AE sedation-reporting tool) represent a mixture of physician  and non-physician professions from 39 countries across six continents . Physicip = 0.0003), age groups: 1–3 (P = 0.0181), 3–5 (p < 0.0001), 50–70 (p < 0.0001), 70–80 (p < 0.0001), procedure time of 12:00–6:00 pm (p = 0.0027), 6:00 pm–12:00 am (p < 0.0001), and 12:00–6:00 am (p = 0.0003), and non-hospital location (p < 0.0001).For those patients who experienced adverse events, the summary statistics of their age and age group distribution are mean age is 32.1 (0.1–98.7) years. Our multivariable model presents 622 adverse events representing outcomes of a total of 164,114 sedations . ReferenWith regards to significant predictors of age, the odds ratio show that age groups 1–2, 3–5, and ≥80 have lower odds of experiencing an AE than those 18–50 years old. The corresponding results of odds ratio and 95% CI is presented visually in n = 63), prolonged (>60 s) Apnea (n = 25), cardiovascular collapse / shock (n = 3), and cardiac arrest/absent pulse (n = 3). There were 389 (62.5%) cases of moderate events: Oxygen desaturation (75–90%) for <60 s (n = 128), and airway obstructions (n = 89). There were 139 (22.3%) cases of minor events: Vomiting/retching (n = 47). There were no cases with minimal risk. No deaths were reported. Sentinel events were analyzed separately to identify predictors of interest with similar results. All sedation providers of sentinel events were contacted to confirm the course and occurrence of events.The identification of adverse events by risk descriptors is summarized in n = 6), atropine to treat bradycardia (n = 4), and chest compressions (n = 5). There were 124 (16.1%) moderate interventions: Oral/nasal airway (n = 51), bag valve mask (positive pressure ventilation) assisted ventilation (n = 49). There were 457 (59.5%) minor interventions: Airway repositioning (n = 183), supplemental (new or elevated concentration) oxygen (n = 147), and tactile stimulation (n = 120). There were 167 (21.7%) minimal interventions; 114 resolved spontaneously without intervention, 24 received additional sedative(s), and 22 received antiemetic. The intervention risks of adverse events are presented in Adverse events and incidence rates per 10,000 with 95% CI are presented in p-value <0.0001. Specific associations between particular sedatives and risks was not able to be evaluated because of the broad spectrum of sedatives and combinations administered, via various routes. All possible sedatives and combinations are available as options on the AE sedation reporting tool. The administration of sedatives , alone or in combination, were the most common choices and are summarized in Creating, implementing, and updating quality improvement data in a collaborative manner has become an important initiative of all published sedation guidelines worldwide. The collection of outcomes is not limited only to deep sedation or monitored anesthesia care, but also extends even to moderate depths of sedation. To date, all published outcome data has represented retrospective reviews of outcome data collected by specific groups of sedation providers, usually representing a single specialty, sedative agent, patient population (adults or children), and occasionally representing a group of varied specialists ,45,46,47This report has highlighted that with multi-specialty providers from a diverse background administering to the extreme spectrums of age for a variety of procedures, the overall risk of sedation is moderate. Almost 15% of all adverse events do not require any intervention. The majority of interventions, when required, are minor and involve airway repositioning most commonly for oxygen desaturation, airway obstruction, or apnea. When sentinel outcomes do occur, they are most likely to involve cardiac arrest, cardiovascular collapse, or oxygen desaturations <75%. Propofol and ketamine delivered as sole agents, are most common with intravenous route strongly favored. Most providers deliver either to adults or children, with only a minority delivering to both populations. In-hospital sedation in the academic setting tends to be more common. The increased risk with higher ASA status is consistent with prior published studies ,48,49. TThe limitations of our study are those shared by all quality assurance and database reports. The data represents only that of the sedation providers who input data. The sedationist makes his/her own determination whether to enter a sedation encounter into the adverse event reporting tool. Each provider may have his/her own threshold and criteria for entering data. As the website is open access and free-of-charge, it is not possible to surmise the rationale of different providers. The intent of the online tool is for sedation providers to tailor its use to his/her particular needs. The tool does not require HIPAA identifiers and the data is collected anonymously (users identity only known to the tool administrator (KPM), all with the intent to encourage “unintimidated” reporting. It is also possible that not every adverse event which occurred during this time period is captured. This is a limitation of all database reports. Particularly as sedation is not commonly captured by electronic medical records, often performed by multi-specialists, the data is unavailable to be extricated electronically. In under-developed areas, electronic medical records are often unavailable and non-existent. Even the most sophisticated of electronic records are unable to accurately capture all events: They may be able to capture physiological vital signs, but fail to document the interventions performed and never are able to record the outcomes.This database is completely founded on clinician self-report and, thus, risks under-reporting of adverse events. There are multiple etiologies for under-reporting: Sedationists may not want to appear to be “poorly performing” by reporting adverse events, some institutions may have policies in place that may generate “punitive” reactions to documented adverse events  and others may simply forget to document the adverse event in the course of providing clinical care because it is not routine practice to use this tool on a regular basis. Thus, the self-reporting of the adverse event reporting tool differentiates this database from others which implement more comprehensive approaches to maximize capture and review of all data. For example, some databases require entry of consecutive cases, ongoing database surveillance, manual audits of randomly selected charts, automated validation checks of their data, and review of interrater reliability prior to data collection and on an ongoing basis.Brief events  may not be captured even by electronic medical records, depending on how frequently these events are recorded. Typically, vital signs and physiological parameters are reported every 5 min. Thus, occurrences within this 5 min window may often go unreported, even electronically. As with any database collecting system, there is a tendency for the reporters to be a self-selected group of individuals who are likely to have some special interest in sedation. Thus, it is possible that these outcomes may not mirror the clinical practice of sedation as a whole.The advantage of the AE reporting tool is that it is the only online, open access, and free-of-charge site that allows providers to not only input their data but also be able to follow and track their own outcomes. Any provider with access to the internet has the ability to report and collect their sedation outcomes. Free of HIPAA identifiers, the user is able to collect data but also still be able to query a particular record if some of the basic specifics of the procedure or event are known. This ability makes the AE tool unique and invaluable to providers, particularly those who lack an organized infrastructure needed to record and collect data as obliged by the Joint Commission and International Joint Commission. The AE tool importantly ensures that all data points are collected, because the user is unable to proceed to the following queries and to complete the data input, unless all data is entered. As adverse events tend to be memorable, as are the associated interventions and outcomes, we believe and assume that those who enter the data have a clear recollection of the event and, often, probably are referring to the patient’s medical records as demographics are included . The database is unusual because a significant proportion of the data includes dental sedation.The adverse event sedation reporting tool as well as this report, represents the monolithic effort of multi-specialty providers from six continents to identify and classify their sedation related outcomes, using definitions that have been standardized and adopted for clinical and research purposes. Our report of an increased risk of adverse events in ASA three or higher, evening sedations, the middle age and elderly adult, and out of hospital procedures, are revealing first steps to guide future studies of sedation-outcome, as well as the design of sedation services.


Prescribing antidepressant drugs is becoming common. These drugs are known to affect sexual functions.The study is aimed to assess the effects of amitriptyline and venlafaxine on sperm parameters and evaluate Malondialdehyde (MDA) and 1, 1-Diphenyl-2-picryl-hydrazyl values in BALB/ mice spermatozoa.Forty adult male BALB/c mice were separated into five groups. Group Ι (control) received distilled water; group ΙΙ amitriptyline (4 mg/kg); group ΙΙΙ amitriptyline (4 mg/kg) +vitamin C (10 mg/kg); group ΙV venlafaxine (2 mg/kg); and group V received vitamin C (10 mg/kg) + venlafaxine (2 mg/kg). All drugs were administered by oral gavage for 35 days. After excision of caudal epididymis, it was located in 1 mL Ham's F10 medium at 37oC for 15 min and then analysis of sperm parameters was performed. To examine lipid peroxidation and total antioxidant capacity, the MDA and 1, 1-Diphenyl-2-picryl-hydrazyl were measured, respectively. The mean sperm parameters in the group treated with amitriptyline were significantly lower than in the other groups. MDA tests showed a significant difference between amitriptyline and control groups (p=0.007). The results of this study showed that amitriptyline consumption can weaken sperm parameters, which can be attributed to the increased production of ROS and toxicity resulting from amitriptyline consumption. Moreover, venlafaxine improved sperm parameters in mice and the lipid peroxidation in this group did not change compared to the control group. Antidepressant drugs are widely used for the treatment of depression, anxiety-related diseases, and stress . The claAmitriptyline is a component of the tricyclic antidepressant family . AmitripDifferent factors increase testicular oxidative stress, including: exposure to pesticides, industrial chemical materials, and high doses of metals like iron, cadmium and lead, as well as several drugs such as antineoplastic drugs, antibacterials, antimalarials, calcium canal blockers, and antidepressants . MalondiSince not much attention has been paid to the effect of antidepressant drugs, especially the SNRL family of drugs, on sperm parameters and lipid peroxidation, the present study aims to examine the impact of amitriptyline and venlafaxine drugs on sperm parameters and on MDA and DPPH levels in BALB/C mice.Animals and treatmentsoC of temperature, and were fed with standard animal chow and water. In this experimental study, 40 adult male BALB/c mice, weighing 20-25 gr and age of 8 wk were obtained from animal house. The mice were kept for 12 hr in light/dark cycle with 22-25Venlafaxine and amitriptyline were obtained from Parsdarou and Abidi Pharmaceutical Company, Iran, respectively. Venlafaxine and vitamin C were dissolved in physiological saline and amitriptyline was dissolved distilled water. The animals were divided into five groups. The group Ι (controls) was treated with distilled water, group ΙΙ received amitriptyline (4 mg/kg) , group ΙEpididymal sperm aspiration and sperm analysis2-bearing incubator. By slowly tearing up the tissue, sperms were extracted and placed in an incubator with 5% CO2 at 37oC for 20 min. To analyze the sperms, viability was evaluated by stained eosin, and then motility and sperm concentration were evaluated via Makler chamber with ×100 magnification optical microscopes . Thirty-five days later, after the mice were killed and the caudal epididymis was brought out, it was placed in 1 mL of culture medium Hams F10, which has been previously placed in the COMotility was classified into progressive (grade a and b: fast and slow) and non-progressive (grade c) spermatozoa. For evaluating normal morphology, stained Papanicolaou was used and 200 spermatozoa were counted using a ×100 magnification light microscope . All theLipid peroxidationThe concentration of the lipid peroxidation product (MDA) or the thiobarbituric acid-reactive substance was determined according to the modified method of Uchiyama and Mihara. In brief, 0.375 ml HCL 20% and 0.375 ml TBA 0.6% were added to 0.1 ml semen plasma. The mixture was heated for 60 min in a boiling water bath. After cooling, 1.25 ml of n-butanol was added, and the mixture was shaken. Thereafter, the mixture was centrifuged at 2000×g for 5 min, and the absorbance of the upper solution was determined at 532 nm .DPPH measurementThe total antioxidant capacity was performed through the trapping of plasma-free radicals by reducing diphenyl-2-picrylhydrazyl. The DPPH stocks were prepared in methanol, which was buffered by acetic acid. The buffered methanol was prepared by mixing 40 mL of acetate buffer 0.1 M to 60 mL of methanol. The other solutions and chemicals were analytic grade. The reaction tubes were wrapped in aluminum foils and kept at 30ºC for 30 min. All measurements were performed at weak light at the wavelength of 517 nm using a spectrophotometer .Ethical considerationThe experimental project was confirmed by the ethics committee of Shahid Sadoughi University of Medical Sciences, Yazd, Iran (IR.SSU.MEDICINE.REC.1394.274). The protocols of the Institutional Animal Care and Use Committee were followed during the course of the experiment in terms of the handling, maintenance, treatment, and killing of the animals.Statistical analysisAll data were analyzed by SPSS software . One-way ANOVA was applied to evaluate the data, and LSD post-test was performed to determine the difference between the two groups. Two-sided p<0.05 indicated a statistically significant difference between sperm evaluations.Sperm parametersThere was a significant difference between groups Ι and ΙV in normal morphology, non-progressive motility, and viability . On the other hand, there was a significant difference between groups Ι and ΙΙ with regard to progressive motility, immotile, sperm concentration and viability parameters .Assessment of Oxidative StressAccording to The mains finding of the present study shows that amitriptyline consumption can weaken sperm parameters. Moreover, venlafaxine can improve sperm parameters in mice.Different studies indicated that antidepressant drugs could have a negative effect on the male reproductive system. However, there is little knowledge of the effect of antidepressant drugs consumption on the ROS production. The purpose of this study is to investigate the influence of antidepressant drugs on sperms parameters and ROS production. In addition, the influence of ROS production on the sperms parameters has been investigated. Our finding showed the toxicity of amitriptyline lead to decrease in the sperm parameters including sperm concentration, progressive motility, and viability. In our study, amitriptyline alone and with vitamin c showed a significant difference in sperm parameters. Actually, consumption of amitriptyline with vitamin c could improve progressive motility, non-progressive motility, viability and decrease immotile. In agreement with our study, Hassanane and co-workers showed a decrease in sperm concentration as well as an increase in morphological abnormalities in the sperm of amitriptyline-treated mice . It has been reported in the literature that the consumption 75-300 mg of trimipramin for 8 wks affects spermatogenesis which is in agreement with our results from amitriptyline-treated mice . The finAlso, no significant change was observed in sperm concentration. Tanrikut and colleagues have analyzed the results of male infertility examination on two men who were receiving the citalopram, sertraline, and venlafaxine. The semen analysis of patient 1 who was receiving citalopram indicated oligospermia and 1% motility.The semen analysis of patient 2 who was receiving sertraline revealed normal volume and no motility sperm . In anotAlthough the exact mechanism of the effects of antidepressant drugs on the reproductive system has not yet been understood well, it has been suggested that neuroendocrine factors may be involved in this mechanism . It has Furthermore, Weydt and colleagues, in 2011, reported a few cases of gynecomastia due to the consumption of venlafaxine and fluoxetine, which were all associated with increased prolactin levels . In anotThe high levels of ROS affect the normal sperm quality  by interacting with lipid membrane, proteins, nuclear and mitochondria DNA. Therefore, in our study to examine the production of ROS by drugs and their effects on the lipid peroxidation and also to evaluate total capacity of antioxidant, the amounts of MDA and DPPH were measured respectively. Our results showed that the seminal plasma DPPH, showed no significant change. However, the result of MDA test between group Ι and ΙΙ, indicated a significant increase. These results are in accordance with Taziki and colleagues that showed amitriptyline led to a significant increase in lipid peroxide in the hepatocytes of rats and the amount of thiobarbituric acid-reactive substance . In 2010Cordero and co-workers reported the mitochondrial cytotoxicity in patients who used amitriptyline . In thisAccording to Abdel-Wahab, venlafaxine is an effective antioxidant against lipid peroxidation damage and increases antioxidant defense line. Also in this study, the amount of MDA decreased in the depression group that was under treatment with venlafaxine . The levAlso, in our study observed that MDA level in group V than in group ΙV, was a significant decline. By considering the lower level of MDA in group V than in group ΙV, it can be concluded that supplemented ascorbic acid in group V improved the effects of lipid peroxidation caused by venlafaxine. In accordance with our results, Ayinde and colleagues reported that daily consumption of supplemented ascorbic acid can decrease stress oxidative and alteration spermatogenesis in albino rats . We obseIn the current study, the use of venlafaxine along with supplemental ascorbic acid significantly decreased lipid peroxidation. Moreover, considering the results of lipid peroxidation and of similar studies done so far on the two drugs, it seems that venlafaxine has less influence on male fertility than amitriptyline due to less ROS production and less influence of drugs on sperm parameters. This study shows that in the amitriptyline-vitamin C-treated mice, the sperm motility is improved and immotile is decreased, while in the venlafaxine-vitamin C-treated mice sperm viability is improved. Ascorbic acid plays an important role in the distinction process of spermatogenesis. The consumption of antioxidants causes conflicts with ROS. ROS might destroy testicular germ cells which leads to a decrease in sperm concentration and an increase in abnormal sperm . It shouGriveau and colleagues showed that ROS increases the lipid peroxidation which causes a decline in sperm mobility and then a reduction in unsaturated fatty acids . In accoAlso, in this study, there was a significant positive correlation between the seminal plasma of ascorbic acid and the concentration, motility, and normal morphology of sperm which are in accordance with the results of Thiele . Hence, Our findings show that the administration of amitriptyline in mice has more detrimental effects on sperm parameters and causes more peroxidation than venlafaxine dose.


High and Low PAb groups also differed on other schizotypy traits, so the specificity of the results to positive schizotypy cannot be assured. Unexpectedly, no group differences were observed on the EFT; however, there was a small, but significant, positive correlation between RFST search efficiency and EFT performance, indicating that they shared some common processes. Overall, the pattern of results suggests that global  processing difficulties may be contributing to the poorer perceptual organization observed in groups with high levels of schizotypy traits. In addition, the confinement of this result to the Target Absent condition suggests that the underlying mechanism involves differences in decisional processes on the RFST between high and low schizotypy groups. The RFST shows promise as a useful tool for measuring specific perceptual organization abilities in non-clinical, and potentially clinical, samples.Perceptual organization (PO) difficulties have repeatedly been reported in people with schizophrenia, and in healthy individuals with high levels of schizotypy traits, who are at increased risk for schizophrenia. In particular, poor performance on the Embedded Figures Test (EFT) has been interpreted as an atypically strong preference for global over local processing, even though these processes cannot be clearly disambiguated on this test. Here we use two separate versions of the Radial Frequency Search Task (RFST), a new index of PO abilities, to selectively investigate global and local processing of shape information in trait schizotypy. Schizotypy traits were assessed using the Wisconsin Schizotypy Scales-Brief. Individuals selected for high and low levels of positive schizotypy [assessed with the Wisconsin Schizotypy Scales-Brief Perceptual Aberration (PAb) scale] completed the EFT, along with the Global RFST and the Local RFST, all of which require participants to find a target shape amongst distractor elements. The High PAb group ( Recently there has been a renewal of interest in problems with perceptual organization (PO) experienced by people with, or at increased risk , for schizophrenia –4. PO inIt has been proposed that PO deficits in schizophrenia are most consistently present when the stimuli used are spatially separated, such as in commonly used contour integration paradigms . Theclosed-contour shape hidden amongst a more complex array , a traditional, though somewhat different, measure of PO, has revealed a common impairment in schizophrenia and high-risk groups , includiex array . Howeverex array —though tex array –12. Despslope of performance, and is used as an indicator of search efficiency. Target Present and Target Absent conditions are also best analyzed separately  and faster reaction times  on the Global RFST, but not the Local RFST. Drawing on prior literature, we expected reaction times to be longer for the Local RFST, compared to the Global RFST  scale . In partbal RFST , indicatbal RFST . To deteTwo thousand six hundred and ninety-three undergraduate students from the University of Western Australia accepted an invitation to complete the Perceptual Aberration , screened positive for the presence of psychotic illness (n = 1), brain injury/disorder (n = 3), or substance abuse (n = 5) on individual interview. Additional exclusion criteria included poor visual acuity  or poor fluency in English (n = 0).The Psychosis Screen  providedMage = 19.39, SDage = 2.75, 17–31 years).Ninety-two participants met the inclusion criteria and were recruited in the High PAb group and 170 participants were recruited in the Low PAb group. The sample was predominantly female (68%), young adults  and Magical Ideation) and Negative  schizotypy were measured using the Wisconsin Schizotypy Scales-Brief , and Disorganized schizotypy was measured with the 11-item Cognitive Disorganization scale of the short-form Oxford-Liverpool Inventory of Feelings and Experiences.The Wisconsin Schizotypy Scales-Brief  and shorThe Autism-Spectrum Quotient (AQ) was used to measure autistic-like traits in the general population . AQ sco2), giving the appearance of sharp-cornered triangles . The number of shapes on the screen (set size) was 1, 2, 4, and 8. The rate of increase in reaction time as set size increased provided a measure of search efficiency, our primary measure of performance on this task.The RFST is a computerized visual search task that measures a participant's ability to as quickly and accurately as possible, find a target amongst distractors. The target and distractors were Radial Frequency (RF) patterns , which aThe Global RFST involved finding an RF3 (triangle-shape) amongst an array of RF4's (square-shaped), which differ in their global properties  and are only distinguishable by local differences in curvature or orientation [see Figure The base radius of the RF patterns was set at 1° [as in ] and the2 and maximum luminance to 90 cd/m2, which was calibrated using an Optical OP 200-E photometer (head model number 265). The viewing distance was sustained by the use of a chin rest 65.5 cm from the screen . The left and right buttons on a CRS CB6 button box were used to make responses.The stimuli for the RFST were created in MatLab 7.0.4 , and were presented using a PC  driving a Sony Trinitron G520 monitor  through the frame buffer of a Cambridge Research Systems (CRS) ViSaGe  visual stimulus generator. The background luminance was set to 45 cd/mA single-interval forced choice reaction time paradigm was used, such that the participant was required to indicate the presence of the target shape via a left (present) or right (absent) button press. The set sizes were randomly interleaved, with the target shape appearing in the display 50% of the time . There were 10 practice trials administered for both versions of the RFST to familiarize participants with the task. There were 120 trials per block, with a total of 90 trials per set size . The blocks of the Global and Local RFST's were interleaved to control for possible practice effects, with the starting block randomized between participants. Reaction time was recorded to 100 μs resolution. Auditory feedback was provided through two different tones, to indicate correct or incorrect responses.The EFT  measureshttp://zhanglab.wikidot.com/handedness), which gives participants a score ranging from −1 (pure left handed) to +1 (pure right handed). A tablet-based version of the digit symbol coding test from the Brief Assessment of Cognition in Schizophrenia  provided a brief but reliable estimate of general cognitive ability . The AQ, all four Wisconsin Schizotypy Scales-Brief subscales and the Cognitive Disorganization subscale were re-administered for test-retest reliability purposes. Only selected High and Low PAb participants completed the EFTnhighPAb = 2, nlowPAb = 2). Outliers (> ± 3 SD) were detected on the digit symbol coding (nlowPAb = 3) and age , and were removed prior to analysis.First a data quality check was conducted. Test-retest reliability for the schizotypy scales was as follows: PAb = 0.73; Social Anhedonia = 0.73, Cognitive Disorganization = 0.84 and AQ = 0.77, indicating good or acceptable reliability for all scales. Screening scores were used for group allocations reported below. Next, individuals who scored 3 or more on the Infrequency Scale were excluded from the final sample . There were no differences in accuracy between the High/Low PAb groups (Present and Absent)  was taken for the EFT. The anti-log of this data is reported in the Results section below. For the RFST, only correct responses were included, and the lower limit of accuracy was set at 75%. All participants met this criterion for the Global RFST, however, a subset of individuals performed below this criterion on the Local RFST, and were subsequently removed from these analyses , for both the Global  and Local  RFST's. Present and Absent data were analyzed separately, as noted above . In addition, since the Global and Local RFST's are targeting independent processes, they were treated as such in the analyses.The slope of the function represents the rate of increase in reaction time as set size increases and therefore provides a measure of search efficiency. t-tests were used to explore group differences in slope and intercepts. Effects sizes are represented by Cohen's d for the independent samples t-tests. Effect sizes are considered small when d = 0.20 or approaches that value, medium when d = 0.50 or approaching that value, and large when approaching d = 0.80  showed that High and Low PAb groups were not significantly different in age, digit symbol coding, handedness or visual acuity. However, compared to the Low PAb groups, the High PAb groups had significantly higher AQ scores and higher levels on all schizotypy traits, except Physical Anhedonia , and EFT average reaction time scores. Correlations larger than 0.3 were used to identify potential covariates , and shIn conclusion, there has been concerted interest in developing reliable and valid tasks for assessing perceptual dysfunction in people with, and at increased risk for, schizophrenia , 72. TheKP, JB, JD, and DB contributed to the development of the study design. JD and DB created the stimuli and programs for collecting data. KP collected and analyzed the data and produced the manuscript, in partial fulfillment of her Ph.D. JB, JD, and DB provided feedback on the manuscript KP, JB, JD, and DB gave final approval and agreed to be accountable for all aspects of the work.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.