Impact of COVID-19 pandemic on care of maintenance hemodialysis patients: a multicenter study.

BACKGROUND: The COVID-19 pandemic posed a challenge to hemodialysis (HD) patients. While most outpatient and elective medical services stopped during lockdown, HD patients continued to visit their dialysis centers. We aimed to assess how the initial phase of the pandemic affected patient care by comparing dialysis adequacy and other parameters of patient care before and during the first 10 months of the COVID-19 pandemic. METHODS: In a retrospective multi-center observational study, all adult dialysis patients in five dialysis centers in Alexandria, Egypt were included. Dialysis adequacy, missed sessions, laboratory parameters and hospitalization were recorded. Data of the 10 months before and the 10 months after the pandemic were compared and predictors of adequacy were determined. RESULTS: In the 388 HD patients included in the study, the number of missed sessions was higher during the pandemic with peaks during the first and second wave of the pandemic. The ratio of patients to nurses, phosphorus and parathormone levels were significantly higher during the pandemic, while urea reduction ratio, Kt/V, hemoglobin, calcium and albumin levels were significantly lower. In patients who reported difficult accessibility, missed HD sessions were higher during lockdown. Hospital admissions doubled during the pandemic, with COVID-19 infection being the main cause (45.5%). Number of patients per nurse and interdialytic weight gain were predictors of inadequate dialysis. CONCLUSION: The COVID-19 pandemic and its related lockdown negatively affected multiple aspects of dialysis patient care. Continued access of optimum care in dialysis patients should be a priority in any future mass events.

Clinical triage of patients on kidney replacement therapy presenting with COVID-19: an ERACODA registry analysis.

BACKGROUND: Patients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes. METHODS: The European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage. RESULTS: Among 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2-7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage. CONCLUSIONS: This study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic.

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry - a retrospective study.

In this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living-related donor (LRD) or living-unrelated donor (LUD). Adult patients in the ERA-EDTA Registry who received their first kidney transplant in 1998-2017 were included. Ten-year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five-year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7-4.6) and 10.8% (95% CI: 10.1-11.5) versus 6.5% (95% CI: 5.7-7.4) and 12.2% (95% CI: 11.2-13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87-1.13) for patient survival and 1.03 (95% CI: 0.94-1.14) for graft survival. Unadjusted risk of death-censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04-1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death-censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.

Be careful with ecological associations.

Ecological studies are observational studies commonly used in public health research. The main characteristic of this study design is that the statistical analysis is based on pooled (i.e., aggregated) rather than on individual data. Thus, patient-level information such as age, gender, income and disease condition are not considered as individual characteristics but as mean values or frequencies, calculated at country or community level. Ecological studies can be used to compare the aggregated prevalence and incidence data of a given condition across different geographical areas, to assess time-related trends of the frequency of a pre-defined disease/condition, to identify factors explaining changes in health indicators over time in specific populations, to discriminate genetic from environmental causes of geographical variation in disease, or to investigate the relationship between a population-level exposure and a specific disease or condition. The major pitfall in ecological studies is the ecological fallacy, a bias which occurs when conclusions about individuals are erroneously deduced from results about the group to which those individuals belong. In this paper, by using a series of examples, we provide a general explanation of the ecological studies and provide some useful elements to recognize or suspect ecological fallacy in this type of studies.

Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis.

Intact FGF23 and α-Klotho during acute inflammation/sepsis in CKD patients.

BACKGROUND: High FGF23 and low α-Klotho levels associate with systemic inflammation and reduced nitric oxide (NO) bioavailability, but the dynamics of this relationship in patients with CKD has not been investigated. METHODS: We sequentially measured serum intact FGF23 and carboxyl-terminal (iFGF23, cFGF23), the iFGF23/cFGF23 ratio, αKlotho, biomarkers of inflammation (hs-CRP, IL-6 and TNF-α) and sepsis (procalcitonin), nitrotyrosine (reflecting NO synthesis and oxidative stress), serum iron and ferritin and CKD-MBD biomarkers, PTH, 25(OH)VD, 1,25(OH)2 VD at peak of intercurrent sepsis and after complete resolution in a series of 17 patients with CKD. RESULTS: At peak infection, biomarkers of inflammation/sepsis, ferritin and nitrotyrosine were all very high (all P < 0·01) and declined towards the normal range thereafter (P < 0·01). iFGF23 was 191 ± 10 pg/ml (geometric mean, SD) and doubled to 371 ± 8 pg/ml (P = 0·003) after the resolution of infection, while cFGF23 did not change (246 ± 5 pg/mL vs. 248 ± 5 pg/mL, P = 0·50). As a consequence, the iFGF23/cFGF23 ratio, an indicator of the proteolytic cleavage of the FGF23 molecule, was 0·78 ± 3·87 at peak infection and increased to 1·49 ± 3·00 after resolution of infection (P < 0·001). In contrast, serum α-Klotho levels were upregulated at peak infection (peak infection: 526 ± 4 pg/ml, postinfection: 447 ± 4 pg/ml, P = 0·001). The eGFR, PTH and vitamin D did not change significantly throughout. CONCLUSIONS: Acute inflammation/sepsis suppresses the active form of FGF23 and activates α-Klotho, the latter effect being likely attributable to enhance proteolysis of FGF23 molecule. iFGF23 downregulation and α-Klotho upregulation during acute sepsis may participate into the counter-regulatory response to severe inflammation in CKD patients with sepsis.

Aldosterone, mortality, cardiovascular events and reverse epidemiology in end stage renal disease.

BACKGROUND: Plasma aldosterone is markedly increased in end stage renal disease (ESRD). The relationship between aldosterone, all-cause and cardiovascular (CV) mortality in observational studies performed so far is controversial. DESIGN: We investigated the relationship between aldosterone, mortality and CV events in multivariate analyses including nutrition status, inflammation, LV function and fluids volume biomarkers in 278 ESRD patients without heart failure at baseline. RESULTS: In univariate analyses aldosterone was an inverse predictor of death (3rd tertile vs. 1st tertile Hazard ratios (HR): 0·58; 95% confidence interval (CI) 0·38-0·90. P = 0·01) and CV events (HR: 0·63; 95% CI 0·41-0·96; P = 0·03). Data adjustment for inflammation and malnutrition biomarkers substantially reduced the inverse relationship between aldosterone, mortality and CV events to be largely not significant (P = 0·31 and P = 0·36, respectively). The same was true by adjusting for volume expansion and LV dysfunction (left atrial volume and atrial natriuretic peptide) biomarkers (P = 0·30 for both outcomes). In a model adjusting for the full set of biomarkers of protein energy wasting/inflammation and volume expansion/LV dysfunction the inverse relationship between aldosterone and death and CV events was nullified (HR for death 0·98, P = 0·93; HR for CV events 0·96, P = 0·87). CONCLUSIONS: Aldosterone is an inverse predictor of mortality and CV events in ESRD patients. This seemingly paradoxical relationship is abolished by statistical adjustment for inflammation, protein energy malnutrition, and volume expansion biomarkers indicating that it is the mere expression of the confounding effect of these factors. A clinical trial is needed to establish if aldosterone antagonism may improve clinical outcomes in ESRD.

Should we extend the application of more frequent dialysis schedules? A 'yes' and a hopeful 'no'.

Observational studies associate long dialysis intervals with an excess risk for mortality and cardiovascular disease hospitalizations. The application alternate day dialysis is an appealing possibility to reduce the cardiovascular burden of long dialysis intervals and a small pilot study demonstrated that this regimen allows safe reduction of dry body weight, BP and left ventricular mass index. However, the actual impact of alternate day hemodialysis and of frequent hemodialysis in general on survival remains unknown. Frequent dialysis schedules may increase the risk of arteriovenous fistula problems and the burden of disease and eventually reduce treatment adherence. Furthermore we cannot safely exclude that more frequent dialysis regimens may be harmful. On the other hand increasing the duration of dialysis and/or frequency of hemodialysis in patients with refractory fluid overload, uncontrolled hypertension, hyperphosphatemia, malnutrition or cardiovascular disease is of unquestionable benefit in these problematic patients.Thus the moderators conclusion to the question being asked is a yes and a hopeful "no". Whenever and wherever possible we should pro-actively apply more frequent dialysis regimens, starting with the alternate day approach, in problematic patients. However, extensive application of frequent hemodialysis schedules is by now unjustified. Evidence that these regimens are beneficial mainly derives from observational studies and the possibility that frequent schedules are harmful cannot be excluded. A clinical trial is needed.

Fitness for entering a simple exercise program and mortality: a study corollary to the exercise introduction to enhance performance in dialysis (EXCITE) trial.

BACKGROUND/AIMS: In this corollary analysis of the EXCITE study, we looked at possible differences in baseline risk factors and mortality between subjects excluded from the trial because non-eligible (n=216) or because eligible but refusing to participate (n=116). METHODS: Baseline characteristics and mortality data were recorded. Survival and independent predictors of mortality were assessed by Kaplan-Meier and Cox regression analyses. RESULTS: The incidence rate of mortality was higher in non-eligible vs. eligible non-randomized patients (21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced after adjustment for risk factors which differed in the two cohorts including age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides, cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to 2.35; P=0.017) and almost nullified after including in the same model also information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513). CONCLUSIONS: Deambulation ability mostly explains the difference in survival rate in non-eligible and eligible non-randomized patients in the EXCITE trial. Extending data analyses and outcome reporting also to subjects not taking part in a trial may be helpful to assess the representability of the study population.

Researchers' Perspectives Regarding Ethical Issues of Biobank Research in the Arab Region.

Background: The recent expansion of genomic biobank research in the Arab region in the Middle East North Africa has raised complex ethical and regulatory issues. However, there is a lack of studies regarding the views of Arab researchers involved in such research. We aimed to assess the perceptions and attitudes of Arab researchers regarding these issues in biobank research. Methods: We developed a questionnaire to assess the perceptions and attitudes regarding genetic research of researchers from Egypt, Sudan, Morocco, and Jordan. The questionnaire requested demographic data, perceptions, and attitudes regarding the collection, storage, and use of biospecimens and data, the use of broad consent, data security, data sharing, and community engagement. We used multiple linear regressions to identify predictors of perceptions and attitudes. Results: We recruited 383 researchers. Researchers favored equally the use of broad and tiered consent (44.1% and 39.1%, respectively). Most respondents agreed with the importance of confidentiality protections to ensure data security (91.8%). However, lower percentages were seen regarding the importance of community engagement (64.5%), data sharing with national colleagues and international partners (60.9% and 41.1%, respectively), and biospecimen sharing with national colleagues and international partners (59.9% and 36.2%, respectively). Investigators were evenly split on whether the return of individual research results should depend on the availability or not of a medical intervention that can be offered to address the genetic anomaly (47.5% and 46.4%, respectively). Predictors of attitudes toward biospecimen research included serving on Research Ethics Committees, prior research ethics training, and affiliation with nonacademic institutions. Conclusions: We recommend further exploratory research with researchers regarding the importance of community engagement and to address their concerns about data sharing, with researchers within and outside their countries.

The ERA Registry Annual Report 2021: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.

Corrigendum: Factors influencing participation in COVID-19 clinical trials: a multinational study.

[This corrects the article DOI: 10.3389/fmed.2021.608959.].

The ERA Registry Annual Report 2020: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with ESKD. This paper is a summary of the ERA Registry Annual Report 2020, also including comparisons among primary renal disease (PRD) groups. Methods: Data were collected from 52 national and regional registries from 34 European countries and countries bordering the Mediterranean Sea: 35 registries from 18 countries providing individual level data and 17 registries from 17 countries providing aggregated data. Using this data, KRT incidence and prevalence, kidney transplantation rates, expected remaining lifetimes and survival probabilities were calculated. Results: A general population of 654.9 million people was covered by the ERA Registry in 2020. The overall incidence of KRT was 128 per million population (p.m.p.). In incident KRT patients, 54% were older than 65 years, 63% were men and the most common PRD was diabetes mellitus (21%). Regarding initial treatment modality in incident patients, 85% received haemodialysis (HD), 11% received peritoneal dialysis (PD) and 4% received a pre-emptive kidney transplant. On 31 December 2020, the prevalence of KRT was 931 p.m.p. In prevalent patients, 45% were older than 65 years, 60% were men and glomerulonephritis was the most common PRD (18%). Of these patients, 58% were on HD, 5% on PD and 37% were living with a kidney transplant. The overall kidney transplantation rate in 2020 was 28 p.m.p., with a majority of kidney grafts from deceased donors (71%). The unadjusted 5-year survival, based on incident dialysis patient from 2011-15, was 41.8%. For patients having received a deceased donor transplant, the unadjusted 5-year survival probability was 86.2% and for patients having received a living donor transplant it was 94.4%. When comparing data by PRD group, differences were found regarding the distribution of age groups, sex and treatment modality received.

Assessing disparities in medical students' knowledge and attitude about monkeypox: a cross-sectional study of 27 countries across three continents.

Background and aims: The recent monkeypox (Mpox) outbreak confirmed by the World Health Organization (WHO) underscores the importance of evaluating the knowledge and attitude of medical students toward emerging diseases, given their potential roles as healthcare professionals and sources of public information during outbreaks. This study aimed to assess medical students' knowledge and attitude about Mpox and to identify factors affecting their level of knowledge and attitude in low-income and high-income countries. Methods: A cross-sectional study was conducted on 11,919 medical students from 27 countries. A newly-developed validated questionnaire was used to collect data on knowledge (14 items), attitude (12 items), and baseline criteria. The relationship between a range of factors with knowledge and attitude was studied using univariate and multivariate analyses. Results: 46% of the study participants were males; 10.7% were in their sixth year; 54.6% knew about smallpox; 84% received the coronavirus disease 2019 (COVID-19) vaccine; and 12.5% had training on Mpox. 55.3% had good knowledge of Mpox and 51.7% had a positive attitude towards it. Medical students in their third, fifth, or sixth year high- income countries who obtained information on Mpox from friends, research articles, social media and scientific websites were positive predictors for good knowledge. Conversely, being male or coming from high-income countries showed a negative relation with good knowledge about Mpox. Additionally, a positive attitude was directly influenced by residing in urban areas, being in the fifth year of medical education, having knowledge about smallpox and a history of receiving the coronavirus disease 2019 (COVID-19) vaccine. Receiving information about Mpox from social media or scientific websites and possessing good knowledge about Mpox were also predictors of a positive attitude. On the other hand, being male, employed, or receiving a training program about Mpox were inversely predicting positive attitude about Mpox. Conclusion: There were differences in knowledge and attitude towards Mpox between medical students in low and high-income countries, emphasizing the need for incorporating epidemiology of re-emerging diseases like Mpox into the medical curriculum to improve disease prevention and control.

Cultural adaptation and validation of the "Kidney Disease and Quality of Life--Short Form (KDQOL-SF™) version 1.3" questionnaire in Egypt.

BACKGROUND: Health Related Quality of Life (HRQOL) instruments need disease and country specific validation. In Arab countries, there is no specific validated questionnaire for assessment of HRQOL in chronic kidney disease (CKD) patients. The aim of this study was to present an Arabic translation, adaptation, and the subsequent validation of the kidney disease quality of life-short form (KDQOL-SFTM) version 1.3 questionnaire in a representative series of Egyptian CKD patients. METHODS: KDQOL-SFTM version 1.3 was translated into Arabic by two independent translators, and then subsequently translated back into English. After translation disparities were reconciled, the final Arabic questionnaire was tested by interviewing 100 pre-dialysis CKD (stage 1-4) patients randomly selected from outpatients attending the Nephrology clinic at the Main Alexandria University Hospital. Test re-test reliability was performed, with a subsample of 50 consecutive CKD patients, by two interviews 7 days apart and internal consistency estimated by Cronbach's α. Discriminant, concept, and construct validity were assessed. RESULTS: All items of SF-36 met the criterion for internal consistency and were reproducible. Of the 10 kidney disease targeted scales, only three had Cronbach's α <0.7: quality of social interaction (0.23), work status (0.28), and cognitive function (0.60). All disease specific scales were reproducible. Results from discriminant validity showed that the study questionnaire could discriminate between patients' subgroups. As for concept validity, the correlation between all domains of the questionnaire with overall health ratewas significant for all domains except for the work status, sexual function, emotional wellbeing, and role emotional. Furthermore, the correlation between the disease specific domains and the two composite summaries of SF-36 (physical and mental composite summaries) was significant for all domains except for sexual function with mental composite summary. Construct validity was indicated by the observation that the majority of the domains of the kidney disease targeted scale of KDQOL-SFTM 1.3 were significantly inter-correlated. Finally, principal component analysis of the kidney disease targeted scale indicated that this part of the questionnaire could be summarized into 10 factors that together explained 70.9% of the variance. CONCLUSION: The results suggest that this Arabic version of the KDQOL-SFTM 1.3 questionnaire is a valid and reliable tool for use in Egyptian patients with CKD.

An overview on standard statistical methods for assessing exposure-outcome link in survival analysis (Part II): the Kaplan-Meier analysis and the Cox regression method.

The Kaplan-Meier and the Cox regression methods are the most used statistical techniques for performing "time to event analysis" in epidemiological and clinical research. The Kaplan-Meier analysis allows to build up one or more survival curves describing the occurrence of the outcome of interest over time according to the presence/absence of one or more exposures. The Cox regression method models the relationship between a specific exposure (either a continuous one like age, and systolic blood pressure or a categorical one like diabetes, degree of obesity, etc.) and the occurrence of a given outcome taking into account multiple confounders and/or predictors.

Prognostic models in the clinical arena.

Making a prognosis is to predict the course of a disease and estimate the probability (or risk) of the appearance of a given outcome in relationship to clinical or non-clinical characteristics. Prognostic assessment is usually modelled by multivariable mathematic equations (prognostic models). In this article we describe what a prognostic model is, how to build a good one, why and how it is important to evaluate its generalizability and accuracy by means of discrimination, calibration and reclassification.

Reliability and validation of an attitude scale regarding responsible conduct in research.

BACKGROUND: Several studies reveal a problematic prevalence of research misbehaviors. There are several potential causes of research misconduct but ensuring that scientists hold attitudes that reflect norms of acceptable behaviors is fundamental. AIM: Our aim was to evaluate the psychometric properties (factor structure and reliability) of an "attitude" scale that we adopted from a questionnaire we previously used to investigate the prevalence of research misbehaviors in the Middle East. METHODS: We used data from participants (n = 254) who were involved in our prior questionnaire study to determine the validity of an attitude scale that we adapted from this previous study. We performed exploratory factor analysis (EFA) to determine the factor structure of the attitude scale followed by measures of convergent and concurrent validity. We assessed reliability by computing the Cronbach's alphas of each construct of the attitude scale. RESULTS: EFA indicated that the attitude scale consists of two factors (constructs). Convergent validity was demonstrated by significant correlations of item-item and item-total. Correlation analysis revealed that the attitude constructs were significantly correlated with the Research Misbehavior Severity Score, thereby demonstrating concurrent validity. Cronbach's alphas were greater than 0.75 for both constructs. CONCLUSION: We demonstrated a valid and reliable 20-item attitude scale with two factors related to "acceptability of practices in responsible conduct in research" and "general attitudes regarding scientific misconduct". The use of a validated attitude scale can help assess the effectiveness of educational programs that focus on participants acquiring attitudes that are instrumental in responsible conduct in research.

Fundamentals and Applications of the Receiver Operating Characteristic Curve Analysis in the Research of Endothelial Dysfunction in Chronic Kidney Disease.

Endothelial dysfunction (ED) starts early in chronic kidney disease (CKD) and is the hallmark of atherosclerosis in these patients. During recent years, numerous markers have emerged, aiming to predict the onset of ED in CKD patients. Therefore, there is a need to evaluate and assess the discriminatory ability (or diagnostic accuracy) of such a marker (i.e., the ability to correctly classify individuals as having a given disease or not) and identify the optimal cut-off value. A receiver operating characteristic (ROC) curve analysis has been used in the majority of the research papers evaluating the predictive ability of a marker of ED. It is a graphical plot combining pairs of sensitivity (true positive rate) on the y axis and the complement of specificity (1-specificity, false positive rate) in the x axis, corresponding to several of the cut-off values covering the complete range of possible values that this test/marker might take. Herein, using a series of practical examples derived from clinical studies on ED in the special population of CKD, we address the principles, fundamentals, advantages and limitations regarding the interpretation of the ROC analysis.