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In confounding, the effect of the exposure of interest is mixed with the effect of another variable. It is important to identify relevant confounders and remove the confounding effect as much as possible. There are three criteria that need to be fulfilled to determine whether a variable could be considered a potential confounder. The first criterion is that the variable needs to be associated with the exposure. The second criterion is that the variable needs to be associated with the outcome or disease. The third criterion is that the variable should not be an intermediate variable in the causal pathway between exposure and outcome. Only if all the criteria are fulfilled is the variable under question a confounder. If one incorrectly adjusts for a variable that is not a confounder, one risks overadjustment or adjustment for spurious associations. Confounders can be prevented from entering the study, during the design of a study, or if this is not possible, one can try to remove it during the analysis phase. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The relationships between the medication prescribed and four measures of morbidity were assessed in 150 Dutch patients with asthma in general practice. Undertreatment was operationalized as a discrepancy between medication and morbidity severity. Of the patients, 11.3% were undertreated as measured by the number of days during which activities were interrupted by asthmatic symptoms. Additional measures such as the number of nights interrupted by asthma, number of attacks and episodes of wheezing, indicated that 28.0%, 24.0% and 34.5% of the patients respectively were undertreated. It is concluded that asthma seems to be undertreated in general practice in The Netherlands, a finding which is consistent with research on this subject in the UK and other countries. Possible reasons for the persistence of undertreatment of asthma are discussed, and suggestions for overcoming it are offered. [ABSTRACT FROM PUBLISHER]

Background: Many patients with asthma or chronic obstructive pulmonary disease use their medication inhalers incorrectly. General practitioners, pharmacists and other health care providers do not always have the opportunity to instruct patients in correct inhaler technique.Objective: To find out whether the inhaler technique and respiratory symptoms of patients can be improved after instruction by practice assistants.Methods: Single blind, randomized intervention study in which 48 patients who had been using a dry powder inhaler for at least one month took part. Their inhaler technique was videotaped on two visits with a two-week interval between visits. The inhaler technique on the videos was subsequently scored by two experts on nine criteria. At both visits the patients completed a questionnaire about their respiratory symptoms. After the first video, 25 patients were randomly chosen to receive instruction from one of six practice assistants who had followed a one evening course about inhaler instruction, and who had been issued an instruction-set.Results: The patients who received instruction had a significantly greater reduction in number of mistakes at the second visit than the patients who did not (P = 0.01). The instructed patients also reported less dyspnoea at the second visit (P = 0.03). No effect of instruction was found on wheezing, cough and sputum production.Conclusion: The inhaler technique of patients can be improved significantly by the instruction of patients by trained practice assistants, possibly resulting in less dyspnoea. [ABSTRACT FROM AUTHOR]

In previous articles of this series, we focused on relative risks and odds ratios as measures of effect to assess the relationship between exposure to risk factors and clinical outcomes and on control for confounding. In randomized clinical trials, the random allocation of patients is hoped to produce groups similar with respect to risk factors. In observational studies, exposed and unexposed individuals may differ not only for the presence of the risk factor being tested but also for a series of other factors that are potentially related to the study outcome, thus making ‘confounding’ very likely. One of the most important uses of multivariate modeling is precisely that ‘of controlling for confounding’ to let emerge the effect of the risk factor of interest on the study outcome. In this paper, we will discuss linear regression analysis for the examination of continuous outcome data and logistic regression analysis for the study of categorical outcome data. Furthermore, we focus on the most important application of multiple linear and logistic regression analyses.Kidney International (2008) 73, 806–810; doi:10.1038/sj.ki.5002787; published online 16 January 2008 [ABSTRACT FROM AUTHOR]

The quality of a clinical study depends on internal and external factors. Studies have internal validity when, random error apart, reported differences between exposed and unexposed individuals can be attributed only to the exposure under investigation. Internal validity may be affected by bias, that is, by any systematic error that occurs in the design or in the conduction of a clinical research. Here we focus on two major categories of bias: selection bias and information bias. We describe three types of selection biases (incidence-prevalence bias, loss-to-follow-up bias, and publication bias) and a series of information biases (i.e. misclassification bias—recall bias, interviewer bias, observer bias, and regression dilution bias—and lead-time bias).Kidney International (2008) 73, 148–153; doi:10.1038/sj.ki.5002648; published online 31 October 2007 [ABSTRACT FROM AUTHOR]

Epidemiological studies aim at assessing the relationship between exposures and outcomes. Clinicians are interested in knowing not only whether a link between a given exposure (e.g. smoking) and a certain outcome (e.g. myocardial infarction) is statistically significant, but also the magnitude of this relationship. The ‘measures of effect’ are indexes that summarize the strength of the link between exposures and outcomes and can help the clinician in taking decisions in every day clinical practice. In epidemiological studies, the effect of exposure can be measured both in relative and absolute terms. The risk ratio, the incidence rate ratio, and the odds ratio are relative measures of effect. Risk difference is an absolute measure of effect and it is calculated by subtracting the risk of the outcome in exposed individuals from that of unexposed.Kidney International (2007) 72, 789–791; doi:10.1038/sj.ki.5002432; published online 25 July 2007 [ABSTRACT FROM AUTHOR]

As confounding obscures the ‘real’ effect of an exposure on outcome, investigators performing etiological studies do their utmost best to prevent or control confounding. Unfortunately, in this process, errors are frequently made. This paper explains that to be a potential confounder, a variable needs to satisfy all three of the following criteria: (1) it must have an association with the disease, that is, it should be a risk factor for the disease; (2) it must be associated with the exposure, that is, it must be unequally distributed between exposure groups; and (3) it must not be an effect of the exposure; this also means that it may not be part of the causal pathway. In addition, a number of different techniques are described that may be applied to prevent or control for confounding: randomization, restriction, matching, and stratification. Finally, a number of examples outline commonly made errors, most of which result from ‘overadjustment’ for variables that do not satisfy the criteria for potential confounders. Such an example of an error frequently occurring in the literature is the incorrect adjustment for blood pressure while studying the relationship between body mass index and the development of end-stage renal disease. Such errors will introduce new bias instead of preventing it.Kidney International (2008) 73, 256–260; doi:10.1038/sj.ki.5002650; published online 31 October 2007 [ABSTRACT FROM AUTHOR]

In studies on the effects of therapy (or other interventions), the randomized controlled trial (RCT) is an almost unbeatable standard in clinical research. The value of RCTs leaves unabated the valuable contributions of observational studies to medicine. This paper discusses some limitations of RCTs providing examples where these are not possible, inappropriate, inadequate, or unnecessary. Thereafter, it focuses on observational studies and gives a number of examples of studies on etiology, diagnosis, prognosis, and adverse effects, where observational designs have provided answers to research questions that could not have been answered by RCTs. Strengths and weaknesses of the different observational study designs are discussed. Finally, it is concluded that both observational studies and RCTs fulfill a complementary and valuable role in nephrology.Kidney International (2007) 72, 671–675; doi:10.1038/sj.ki.5002397; published online 27 June 2007 [ABSTRACT FROM AUTHOR]

The purpose of this paper is to discuss whether the randomized clinical trial (RCT) is indeed the gold standard among epidemiological studies. This paper illustrates to what extent different study designs may contribute to the answer of the following therapeutic research question based on a study of Wanner et al.: ‘Is the use of a statin associated to less cardiac mortality in patients with type 2 diabetes mellitus who receive hemodialysis?’ If a therapeutic study is feasible, like the research question of the clinical example, the RCT is almost unbeatable: the problems that may occur in the other study designs do not exist or to a lesser extent using an RCT. The main advantage of an RCT is that the randomization procedure helps to prevent selection bias by the clinician by breaking the link between the clinician's therapy prescription and the patient's prognosis. Within observational studies, however, selection by the clinician may occur, and, even after adjustment for potential confounders in the statistical analysis, it may not be possible to make a fair comparison between the groups. Usually, results from observational studies are needed to come to a hypothesis that can subsequently be tested within an RCT. Moreover, observational data are most often more useful than RCTs for non-therapeutic studies.Kidney International (2007) 72, 539–542; doi:10.1038/sj.ki.5002354; published online 27 June 2007 [ABSTRACT FROM AUTHOR]

Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over-immunosuppression, and lower loads to under-immunosuppression. This review offers an overview of the current evidence of the association between TTV-load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer-reviewed articles were assessed investigating the association between TTV-load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)-tool was used to assess the risk of bias. Meta-analysis with random-effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV-load was measured longitudinally, within the first 2 years post-transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV-load and infections, whereas 13 out of 15 reported an association between low TTV-load and rejection. Meta-analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03-1.32; HR: 1.05, 95% CI: 0.97-1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87-0.94; HR: 0.74, 95% CI: 0.71-0.76) per 1 log TTV-load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta-analysis indicates that blood TTV-load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT., (© 2022 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd.)

Proton pump inhibitors are widely used, and generally considered safe. In this clinical lesson two cases are presented with a strong suspicion of proton pump inhibitor induced decline of kidney function. This adverse event has only recently been identified in epidemiological studies. Our cases illustrate that chronic proton pump inhibitor nephrotoxicity can manifest subtle and may therefore be difficult to recognize. We discuss the current epidemiological evidence to support these observations, and the pathophysiology and clinical manifestations of proton pump inhibitor nephrotoxicity. In case a subject using a proton pump inhibitor shows kidney function decline, without a clear cause, withdrawal of this medication is advised. Although for an individual patient the risk may not be high, the large number of proton pump users makes that this adverse event is important on a population level.

Introduction: Preservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality., Methods: We conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined., Results: One hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (-28.0 ml/min per year; 95% CI: -60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (-291 ml/min per year; 95% CI: -550 to -32) while this was absent in biocompatible treatment., Conclusion: Despite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Background: The potential benefit of surgery of the primary tumour in patients with asymptomatic metastatic colorectal cancer is debated. This EURECCA international comparison analyses treatment strategies and overall survival in the Netherlands and Norway in patients with incurable metastatic colorectal cancer., Methods: National cohorts (2007-2013) from the Netherlands and Norway including all patients with synchronous metastatic colorectal cancer were compared on treatment strategy and overall survival. Using country as an instrumental variable, we assessed the effect of different treatment strategies on mortality in the first year., Results: Of 21,196 patients (16,144 Dutch and 5052 Norwegian), 38.6% Dutch and 51.5% (p < 0.001) Norwegian patients underwent resection of the primary tumour. In the Netherlands, 58.2% received chemotherapy compared with 21.4% in Norway. Radiotherapy was given in 9.5% of Dutch patients and 7.2% of Norwegian patients. Using the Netherlands as reference, the adjusted HR for overall survival was 0.96 (95% CI 0.93-0.99; p = 0.024). Instrumental variable analysis showed an adjusted OR of 1.00 (95% CI 0.99-1.02; p = 0.741)., Conclusions: Treatment strategies varied significantly between the Netherlands and Norway, with more surgery and less radiotherapy in Norway. Adjusted overall survival was better in Norway for all patients and patients <75 years, but not for patients ≥75 years. Instrumental variable analysis showed no benefit in one-year mortality for a treatment strategy with a higher proportion of surgery and a lower proportion of radiotherapy. Our findings emphasise the need for further research to select patients with incurable metastatic colorectal cancer for different treatment options., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Essentials Mortality due to bleeding vs. arterial thrombosis in dialysis patients is unknown. We compared death causes of 201 918 dialysis patients with the general population. Dialysis was associated with increased mortality risks of bleeding and arterial thrombosis. Clinicians should be aware of the increased bleeding and thrombosis risks., Summary: Background Dialysis has been associated with both bleeding and thrombotic events. However, there is limited information on bleeding as a cause of death versus arterial thrombosis as a cause of death. Objectives To investigate the occurrence of bleeding, myocardial infarction and stroke as causes of death in the dialysis population as compared with the general population. Methods We included 201 918 patients from 11 countries providing data to the ERA-EDTA Registry who started dialysis treatment between 1994 and 2011, and followed them for 3 years. Age-standardized and sex-standardized mortality rate ratios for bleeding, myocardial infarction and stroke as causes of death were calculated in dialysis patients as compared with the European general population. Associations between potential risk factors and these causes of death in dialysis patients were investigated by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) by the use of Cox proportional-hazards regression. Results As compared with the general population, the age-standardized and sex-standardized mortality rate ratios in dialysis patients were 12.8 (95% CI 11.9-13.7) for bleeding as a cause of death (6.2 per 1000 person-years among dialysis patients versus 0.3 per 1000 person-years in the general population), 13.4 (95% CI 13.0-13.9) for myocardial infarction (22.5 versus 0.9 per 1000 person-years), and 12.4 (95% CI 11.9-12.9) for stroke (14.3 versus 0.7 per 1000 person-years). Conclusion Dialysis patients have highly increased risks of death caused by bleeding and arterial thrombosis as compared with the general population. Clinicians should be aware of the increased mortality risks caused by these conditions., (© 2018 International Society on Thrombosis and Haemostasis.)

Background: More older patients with end-stage renal disease (ESRD) are starting dialysis. Elderly patients often prefer treatments that focus on quality of life rather than primarily extending life and a substantial group of elderly dialysis patients might regret their decision to start dialysis. Healthcare provider and patient-related factors may be involved. Our objective was to measure the percentage of patients in the Netherlands who regretted their decision to start dialysis., Methods: Cross-sectional Dutch national survey of dialysis patients. A short questionnaire about age, satisfaction with pre-dialysis education, present treatment, dialysis initiation, regret about decision to start dialysis and key figures in decision-making was developed., Results: A total of 1371 questionnaires were returned for analysis from 28 dialysis units. Of the patients 7.4% regretted their decision to start dialysis, 50.5% reported the nephrologist's opinion to be crucial in decision-making and these patients experienced more regret than those who made the decision themselves (odds ratio, OR: 1.81). When family influenced decision-making more regret was experienced compared with those who decided themselves (OR: 2.73). Older age was associated with less regret (p = 0.02) and higher treatment satisfaction (p < 0.001); 52.8% of participants described dialysis initiation as being sudden., Conclusion: The majority of patients did not regret their decision to start dialysis. Older patients were more satisfied with their treatment and felt less regret. The nephrologist's and the family's opinion were directional in decision-making on ESRD treatment options and were associated with more regret, especially in younger patients.

The share of peritoneal dialysis (PD) in the spectrum of chronic dialysis has decreased markedly in the Netherlands in the last 15 years. Consequently, the knowledge of nephrologists and nursing staff on PD has declined leading to a negative spiral in which loss of experience resulted in loss of enthusiasm to offer PD to patients and also in less interest in the new PD developments. All these changes took place while the results of PD improved and patient survival was at least similar to that on haemodialysis. The aim of this review is first to give a summary of the principles and practice of patient and staff education and to describe the role of the medical contribution in decision-making. On this basis, the second aim is to update internist-nephrologists on a number of issues that have been underexposed in the past. Recent patient and technique survival data of PD patients is reviewed, and also the new insights into dialysis adequacy. The presence of residual renal function is the main determinant of patient survival together with prevention of overhydration. Urea and creatinine removal are not important at all when patients are still passing urine. Many early problems with PD are due to the peritoneal catheter and suggestions are made for improvement of its function. The prevention and management of infections is reviewed, and also the regular assessment of peritoneal function. Free water transport is a predictor of encapsulating peritoneal sclerosis (EPS), which should be assessed regularly. The pathogenesis of EPS, treatment and the decreasing incidence are discussed.

Physicians need to stay up-to-date with new developments in their field of expertise. This expectation has been made explicit by competency-based educational outcomes in the domain of scholar in the Dutch blueprint. There is a great diversity in teaching methods that aim to achieve a better understanding of scientific knowledge. Applying a constructivist approach to learning in acquiring research competencies we wonder how a research-intensive course is evaluated early in the curriculum and what learning gain students perceive. In a collaborative research-intensive course, the class of 300s-year students rated the quality of 150 preselected randomized controlled trials (RCT) using JAMA Users' Guides, and the pharmaceutical advertisements in which they were referenced. Each student rated two RCTs. Data were analyzed to answer a relevant research question. After the course students completed an evaluation survey. We did this in five consecutive years to capture student experience in relation to fostering a scientific mindset (n = 1,500). In addition we studied outcome of this scientific mindset as scientific output (publications) in journals. Survey data indicate that it is feasible to successfully implement a research-intensive course based on a large cohort using a constructivist paradigm early in the curriculum. Students consider it challenging and report high learning gain in several domains. Aggregated data have even led to four publications in journals. Implementing an active learning research experience early in the curriculum can foster student attitudes, provided the level of difficulty correctly matches the learners' prior knowledge. Further research is required to determine how to improve these active research curricula to maximize impact on learners.

Aims/hypothesis: A previous study in Dutch dialysis patients showed no survival difference between patients with diabetes as primary renal disease and those with diabetes as a co-morbid condition. As this was not in line with our hypothesis, we aimed to verify these results in a larger international cohort of dialysis patients., Methods: For the present prospective study, we used data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry. Incident dialysis patients with data on co-morbidities (n = 15,419) were monitored until kidney transplantation, death or end of the study period (5 years). Cox regression was performed to compare survival for patients with diabetes as primary renal disease, patients with diabetes as a co-morbid condition and non-diabetic patients., Results: Of the study population, 3,624 patients (24%) had diabetes as primary renal disease and 1,193 (11%) had diabetes as a co-morbid condition whereas the majority had no diabetes (n = 10,602). During follow-up, 7,584 (49%) patients died. In both groups of diabetic patients mortality was higher compared with the non-diabetic patients. Mortality was higher in patients with diabetes as primary renal disease than in patients with diabetes as a co-morbid condition, adjusted for age, sex, country and malignancy (HR 1.20, 95% CI 1.10, 1.30). An analysis stratified by dialysis modality yielded similar results., Conclusions/interpretation: Overall mortality was significantly higher in patients with diabetes as primary renal disease compared with those with diabetes as a co-morbid condition. This suggests that survival in diabetic dialysis patients is affected by the extent to which diabetes has induced organ damage.

Background: Although an association between venous thrombosis and chronic kidney disease has recently been established, it is unknown which patients with chronic kidney disease are most likely to benefit from thromboprophylaxis., Objective: The aim of this study was to assess the association between venous thrombosis and chronic kidney disease in combination with arterial thrombosis, malignancy, surgery and thrombophilia to identify high-risk groups as a basis for personalized prevention., Methods: This study included 2473 consecutive patients with first venous thrombosis and 2936 controls from a case-control study (the MEGA study)., Results: Moderately decreased kidney function (eGFR 30-60 mL min(-1) ) was associated with a 2.5-fold (95% CI, 1.9-3.4) increased risk and severely decreased kidney function (eGFR < 30 mL min(-1) ) was associated with a 5.5-fold (95% CI 1.8-16.7) increased risk of venous thrombosis, compared with those with normal kidney function (eGFR > 90 mL min(-1) ). The risk of venous thrombosis was additionally increased for moderately and severely reduced kidney function in combination with arterial thrombosis (odds ratio, 4.9; 95% CI, 2.2-10.9), malignancy (5.8; 95% CI, 2.8-12.1), surgery (14.0; 95%, CI 5.0-39.4), immobilization (17.1; 95% CI, 6.8-43.0) or thrombophilia (odds ratios, 4.3-9.5), with particularly high risks when three or more risk factors were present (odds ratio, 56.3; 95% CI, 7.6-419.3)., Conclusion: Decreased kidney function is associated with an increased risk of venous thrombosis. The risk increased substantially in the presence of one or more other risk factors for thrombosis., (© 2013 International Society on Thrombosis and Haemostasis.)

Background: The risk of venous thrombosis associated with major illnesses is not well known, and neither is the risk associated with the combined effect of immobilization and thrombophilia. The aim of this study was to assess the effect on the development of venous thrombosis of several major illnesses in combination with immobilization, body mass index, and thrombophilia, to identify high-risk groups that may provide a basis for personalized prevention., Methods: This study included 4311 consecutive patients with a first episode of venous thrombosis, and 5768 controls from a case-control study (MEGA study). We calculated odds ratios (ORs) for venous thrombosis for patients with a self-reported history of major illnesses., Results: Venous thrombosis risk was increased for all investigated major illnesses: liver disease, OR 1.7 (95% confidence interval [CI]1.0-2.9); kidney disease, OR 3.7 (95% CI 2.3-5.9); rheumatoid arthritis, OR 1.5 (95% CI 1.2-1.9); multiple sclerosis, OR 2.4 (95% CI 1.3-4.3); heart failure, OR 1.7 (95% CI 1.2-2.3); hemorrhagic stroke, OR 4.9 (95% CI 2.4-9.9); arterial thrombosis, OR 1.5 (95% CI 1.2-1.8); and the presence of any of the above major illnesses, OR 1.7 (95% CI 1.5-1.9). Combinations of major illnesses with immobilization and increased factor VIII (OR 79.9; 95% CI 33.2-192.2), increased FIX (OR 35.3; 95% CI 14.2-87.8), increased von Willebrand factor (OR 88.0; 95% CI 33.9-228.3), FV Leiden (OR 84.2; 95% CI 19.5-363.6), and blood group non-O (OR 53.1; 95% CI 30.9-91.4) were associated with increased venous thrombosis risks., Conclusions: All of the major illnesses reported here were associated with an increased risk of venous thrombosis. These risks were most pronounced at the time of immobilization or in the presence of thrombophilia., (© 2012 International Society on Thrombosis and Haemostasis.)

Unlabelled: The success of universal newborn hearing screening (UNHS) programmes is usually evaluated by determining the effect of the early detection of hearing loss on developmental outcome. However, in practice, these programmes do not detect all children with permanent childhood hearing impairment. In this study we determine the sensitivity of the current UNHS programme and analyse the characteristics of the children not detected by UNHS. We performed a nationwide, population-based, retrospective follow-up study in The Netherlands. All children born in 2003-05 and screened in a hearing screening programme (well babies and neonatal intensive care (NICU) graduates) were included for study. The main outcome measure was the sensitivity of the UNHS programme (based on the proportion of children known to have a permanent childhood hearing impairment in 2008 who were identified by UNHS). We also evaluated age at diagnosis, severity, and aetiology of hearing impairment in the children not detected by UNHS. We found that the sensitivity of the current UNHS programme was 0.83 (0.79 for well babies and 0.96 for NICU graduates). Permanent childhood hearing impairment was confirmed before 36 months of age in 96% of the study cohort. Of the children unidentified by the UNHS, > 50% had moderate hearing loss. No predominant cause of hearing impairment was found in these children., Conclusion: Our current UNHS programme identified the majority of children with a permanent hearing impairment of congenital cause.

Background: It is has been suggested that dialysis patients have lower mortality rates for pulmonary embolism than the general population, because of platelet dysfunction and bleeding tendency. However, there is limited information whether dialysis is indeed associated with a decreased mortality risk from pulmonary embolism., Objective: The aim of our study was to evaluate whether mortality rate ratios for pulmonary embolism were lower than for myocardial infarction and stroke in dialysis patients compared with the general population., Methods: Cardiovascular causes of death for 130,439 incident dialysis patients registered in the ERA-EDTA Registry were compared with the cardiovascular causes of death for the European general population., Results: The age- and sex-standardized mortality rate (SMR) from pulmonary embolism was 12.2 (95% CI 10.2-14.6) times higher in dialysis patients than in the general population. The SMRs in dialysis patients compared with the general population were 11.0 (95% CI 10.6-11.4) for myocardial infarction, 8.4 (95% CI 8.0-8.8) for stroke, and 8.3 (95% CI 8.0-8.5) for other cardiovascular diseases. In dialysis patients, primary kidney disease due to diabetes was associated with an increased mortality risk due to pulmonary embolism (HR 1.9; 95% CI 1.0-3.8), myocardial infarction (HR 4.1; 95% CI 3.4-4.9), stroke (HR 3.5; 95% CI 2.8-4.4), and other cardiovascular causes of death (HR 3.4; 95% CI 2.9-3.9) compared with patients with polycystic kidney disease., Conclusions: Dialysis patients were found to have an unexpected highly increased mortality rate for pulmonary embolism and increased mortality rates for myocardial infarction and stroke., (© 2012 International Society on Thrombosis and Haemostasis.)

In medicine, before replacing an old device by a new one, we need to know whether the results of the old and new device are similar. This is called determining the agreement between methods. In this paper, we will first discuss various ways to determine the agreement between methods to measure continuous variables, including the t test, the correlation coefficient and the Bland-Altman plot. In the second part, we will discuss methods to determine the agreement between categorical variables, like the χ(2) test and Cohen's ĸ. The latter are often used when studying the agreement between clinicians, definitions, formulas or different data sources., (Copyright © 2012 S. Karger AG, Basel.)

The most frequently used model to describe the exponential increase in mortality rate over age is the Gompertz equation. Logarithmically transformed, the equation conforms to a straight line, of which the slope has been interpreted as the rate of senescence. Earlier, we proposed the derivative function of the Gompertz equation as a superior descriptor of senescence rate. Here, we tested both measures of the rate of senescence in a population of patients with end-stage renal disease. It is clinical dogma that patients on dialysis experience accelerated senescence, whereas those with a functional kidney transplant have mortality rates comparable to the general population. Therefore, we calculated the age-specific mortality rates for European patients on dialysis (n=274 221; follow-up=594 767 person-years), for European patients with a functioning kidney transplant (n=61 286; follow-up=345 024 person-years), and for the general European population. We found higher mortality rates, but a smaller slope of logarithmic mortality curve for patients on dialysis compared with both patients with a functioning kidney transplant and the general population (P<0.001). A classical interpretation of the Gompertz model would imply that the rate of senescence in patients on dialysis is lower than in patients with a functioning transplant and lower than in the general population. In contrast, the derivative function of the Gompertz equation yielded the highest senescence rates for patients on dialysis, whereas the rate was similar in patients with a functioning transplant and the general population. We conclude that the rate of senescence is better described by the derivative function of the Gompertz equation., (© 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)