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Objective: The aim of this study was to explore the changes in nutritional status before dialysis initiation and to identify modifiable risk factors of nutritional status decline in older adults with advanced renal disease.& nbsp;Design and Methods: The European Quality Study on treatment in advanced chronic kidney disease (EQUAL) is a prospective, observational cohort study involving six European countries. We included 1,103 adults > 65 years with incident estimated glomerular filtration rate < 20 mL/min/1.73 m(2) not on dialysis, attending nephrology care. Nutritional status was assessed with the 7-point Subjective Global Assessment tool (7-p SGA), patient-reported outcomes with RAND-36 and the Dialysis Symptom Index. Logistic regression was used to estimate the associations between potential risk factors and SGA decline.& nbsp;Results: The majority of the patients had a normal nutritional status at baseline, 28% were moderately malnourished (SGA = 2 points). The proportion of patients with low SGA (

Background Hospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young ( Methods We included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders. Results Among 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly. Conclusion A lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs.

Background People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study. Methods The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy. Results Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73–4.37]; P Conclusions Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.

Background: To investigate the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular outcomes in routine clinical practice, which have never been directly compared in head-to-head outcome trials. Methods: We compared outcomes of adults who newly started SGLT2i or GLP1-RA therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular (CV) death, myocardial infarction and stroke. Secondary outcomes included the individual MACE components and hospitalization for heart failure. Cox regression with propensity score overlap weighting was used to estimate hazard ratios (HRs) with 95% confidence intervals and adjust for 57 covariates. Results: We included 12,375 individuals, of which 5489 initiated SGLT2i and 6886 GLP1-RA therapy, followed for median 1.6 years. Mean age was 61 years and 37.6% were women. Compared with GLP1-RA, SGLT2i new users had similar risk of MACE risk (adjusted HR 1.04; 95% CI 0.83-1.31). The adjusted HRs (95% CI) for SGLT2i vs. GLP1-RA were 0.80 (0.59-1.09) for heart failure hospitalization, 0.95 (0.58-1.55) for cardiovascular death, 0.91 (0.67-1.24) for myocardial infarction and 1.71 (1.14-2.59) for ischemic stroke (5-year absolute risk dif-ference for stroke 1.9% [95% CI 0.8-3.0]). Conclusions: In a largely primary-prevention population of people undergoing routine care, no differences were observed in MACE risk among initiators of SGLT2i and GLP1-RA. However, compared with GLP1RA, the use of SGLT2i was associated with an increased risk of ischemic stroke that was small in absolute magnitude.

Background Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. Methods This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory – second edition (BDI-II), with a cut-off score of ≥10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. Discussion If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. Trial registration Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

Background Persistent, low-grade inflammation likely participates in the pathophysiology of both atherosclerosis and kidney disease. Although high-sensitivity C-reactive protein (hsCRP) predicts future cardiovascular risk in patients with chronic kidney disease (CKD), it is unknown whether hsCRP levels predict adverse renal outcomes in patients with cardiovascular disease.Methods We studied all myocardial infarction (MI) survivors undergoing hsCRP testing >30 days after their MI during routine health care in Stockholm, Sweden (2006-2011), with available information on estimated glomerular filtration rate (eGFR). HsCRP tests measured during hospitalization/emergency room visits, followed by antibiotics or indicative of acute illness, were excluded, together with patients with ongoing/recent cancer, chronic infections, or immunosuppression. Inflammation was defined over a 3-month baseline window. Study outcomes were CKD progression (composite of doubling plasma creatinine, renal replacement therapy, or renal death) and acute kidney injury (AKI, acute creatinine peaks according to Kidney Disease: Improving Global Outcomes criteria). Multivariable Cox regression was used to adjust for age, sex, eGFR, hemoglobin, time since MI, comorbidities, undertaken procedures, and medications.Results A total of 12,905 patients (62% men, mean age 73 years and 3 years since MI) were included, of whom 35% had an eGFR= 2 mg/L were at higher risk of both CKD progression (adjusted hazard ratio 1.42; 95% CI 1.21-1.66) and AKI (1.29; 1.13-1.47) compared to those with hsCRP 10 mg/L). Results were robust across subgroups of patients and after exclusion of events occurring during the first 6-12 months.Conclusions In post-MI patients undergoing routine health care, elevated hsCRP was associated with subsequent risk of AKI and progression of CKD, irrespective of baseline kidney function.

Supplemental digital content is available in the text., Objective Unraveling specific dimensions of depressive symptoms may help to improve screening and treatment in dialysis patients. We aimed to identify the best-fitting factorial structure for the Beck Depression Inventory-II (BDI) in dialysis patients and to assess the relation of these structure dimensions with quality of life (QoL), hospitalization, and mortality. Methods This prospective study included chronic dialysis patients from 10 dialysis centers in five hospitals between 2012 and 2017. Dimensions of depressive symptoms within the BDI were analyzed using confirmatory factor analysis. To investigate the clinical impact of these dimensions, the associations between symptom dimensions and QoL, hospitalization rate, and mortality were investigated using logistic, Poisson, and Cox proportional hazard regression models. Multivariable regression models included demographic, social, and clinical variables. Results In total, 687 dialysis patients were included. The factor model that included a general and a somatic factor provided the best-fitting structure of the BDI-II. Only the somatic dimension scores were associated with all-cause mortality (hazard ratio of 1.7 [1.2–2.5], p < .007) in the multivariable model. All dimensions were associated with increased hospitalization rate and reduced QoL. Conclusions The somatic dimension of the BDI-II in dialysis patients was associated with all-cause mortality, increased hospitalization rate, and reduced QoL. Other dimensions were associated with hospitalization rate and decreased QoL. These findings show that symptom dimensions of depression have differential association with adverse clinical outcomes. Future studies should take symptom dimensions into account when investigating depression-related pathways, screening, and treatment effects in dialysis patients.

Rationale & Objective: It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy.Study Design: Observational study in the Swedish Renal Registry, 2007 to 2017.Settings & Participants: 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates < 30 mL/min/1.73 m(2) (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60 mL/min/1.73 m(2)) were evaluated.Exposures: RAS inhibitor versus CCB therapy initiation.Outcome: Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke).Analytical Approach: HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates.Results: Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs.Limitations: Potential confounding by indication.Conclusions: Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.

IntroductionExtracurricular research programmes (ERPs) may contribute to reducing the current shortage in physician-scientists, but usually select students based on grades only. The question arises if students should be selected based on their motivation, regardless of their previous academic performance. Focusing on grades and lacking to take motivation into account when selecting students for ERPs might exclude an important target group when aiming to cultivate future physician-scientists. Therefore, this study compared ERP students with lower and higher previous academic performance on subsequent academic performance, ERP performance, and motivational factors.MethodsProspective cohort study with undergraduate medical students who filled in a yearly questionnaire on motivational factors. Two student groups participating in an ERP were compared: students with first-year grade point average (GPA) ≥7 versus ResultsThe ConclusionsSince intrinsic motivation for research, perceptions of research, and curiosity are prerequisites of future research involvement, it seems beneficial to focus on motivation when selecting students for ERPS, allowing students with lower current academic performance to participate in ERPs as well.

BACKGROUND: It is unknown whether stopping renin-angiotensin system (RAS) inhibitor therapy in patients with advanced CKD affects outcomes. METHODS: We studied patients referred to nephrologist care, listed on the Swedish Renal Registry during 2007–2017, who developed advanced CKD (eGFR

Background: It is unknown if β-blockers reduce mortality/morbidity in patients with heart failure (HF) and advanced chronic kidney disease (CKD), a population underrepresented in HF trials. Methods: Observational cohort of HF patients with advanced CKD (estimated glomerular filtration rate 2 ) from the Swedish Heart Failure Registry between 2001 and 2016. We first explored associations between β-blocker use, 5-year death, and the composite of cardiovascular death/HF hospitalization among 3775 patients with HF with reduced ejection fraction (HFrEF) and advanced CKD. We compared observed hazards with those from a control cohort of 15 346 patients with HFrEF and moderate CKD (estimated glomerular filtration rate 2 ), for whom β-blocker trials demonstrate benefit. Second, we explored outcomes associated to β-blocker among advanced CKD participants with preserved (HFpEF; N=2009) and midrange ejection fraction (HFmrEF; N=1514). Results: During a median follow-up of 1.3 years, 2012 patients had a subsequent HF hospitalization, and 2849 died in the HFrEF cohort, of which 2016 died due to cardiovascular causes. Among patients with HFrEF, β-blocker use was associated with lower risk of death (adjusted hazard ratio 0.85 [95% CI, 0.75–0.96]) and cardiovascular mortality/HF hospitalization (0.87 [0.77–0.98]) compared with nonuse. The magnitude of the associations was similar to that observed for HFrEF patients with moderate CKD. Conversely, no significant association was observed for β-blocker users in advanced CKD with HFpEF (death: 0.88 [0.77–1.02], cardiovascular mortality/HF hospitalization: 1.05 [0.90–1.23]) or HFmrEF (death: 0.95 [0.79–1.14], cardiovascular mortality/HF hospitalization: 1.09 [0.90–1.31]). Conclusions: In HFrEF patients with advanced CKD, the use of β-blockers was associated with lower morbidity and mortality. Although inconclusive due to limited power, these benefits were not observed in similar patients with HFpEF or HFmrEF.

Background Research is of great value to make advancements within the medical field and, ultimately, offer the best possible patient care. Physician-scientists are key in contributing to the development of medicine, as they can bridge the gap between research and practice. However, medicine currently faces a physician-scientist shortage. A possible solution to cultivate physician-scientists is to engage medical students in research in early phases of medical school. Evidence-based strategies to stimulate positive perceptions of and motivation for research among students could help to enhance research engagement. Consequently, understanding of students’ perceptions of and motivation for research is needed. Therefore, this study aimed to identify conditions under which students develop positive perceptions of and motivation for research by answering the following sub-questions: 1) how do first-year medical students perceive research? and 2) which factors contribute to motivation or demotivation for conducting research? Methods We conducted a qualitative study with individual interviews using a grounded theory approach, involving 13 purposively sampled first-year medical students at Leiden University Medical Center. Results Our results suggest that first-year students are already able to identify many aspects of research. Students elaborated on the relevance of research for professional practice and personal development. Furthermore, our results suggest a relationship between perceptions of and motivation for research. Some perceptions were identical to motivating or demotivating factors to conduct research, like the relevance of research for practice and performing statistics respectively. Other motivating factors were, among others, acknowledgment, autonomy, and inspiring role models. Demotivating factors were, among others, lack of autonomy and relevance, and inadequate collaboration. Conclusions Our results contribute to the idea that perceptions of research are related to motivation for research, which offers possibilities for interventions to promote motivation for research by making use of student perceptions of research. Consequently, practical implications to stimulate research engagement in early phases of medical school are provided. Moreover, the results contribute to existing motivational theories like Theory of Planned Behavior and Self-Determination Theory within this specific domain.

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. 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. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background Bleeding risk scores have been created to identify patients with an increased bleeding risk, which could also be useful in dialysis patients. However, the predictive performances of these bleeding risk scores in dialysis patients are unknown. Therefore, the aim of this study was to validate existing bleeding risk scores in dialysis patients. Methods A cohort of 1745 incident dialysis patients was prospectively followed for 3 years during which bleeding events were registered. We evaluated the discriminative performance of the Hypertension, Abnormal kidney and liver function, Stroke, Bleeding, Labile INR, Elderly and Drugs or alcohol (HASBLED), the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), the Hepatic or kidney disease, Ethanol abuse, Malignancy, Older age, Reduced platelet count or Reduced platelet function, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) and the Outcomes Registry for Better Informed Treatment (ORBIT) bleeding risk scores by calculating C-statistics with 95% confidence intervals (CI). In addition, calibration was evaluated by comparing predicted and observed risks. Results Of the 1745 dialysis patients, 183 patients had a bleeding event, corresponding to an incidence rate of 5.23/100 person-years. The HASBLED [C-statistic of 0.58 (95% CI 0.54–0.62)], ATRIA [C-statistic of 0.55 (95% CI 0.51–0.60)], HEMORR2HAGES [C-statistic of 0.56 (95% CI 0.52–0.61)] and ORBIT [C-statistic of 0.56 (95% CI 0.52–0.61)] risk scores had poor discriminative performances in dialysis patients. Furthermore, the calibration analyses showed that patients with a low risk of bleeding according to the HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had higher incidence rates for bleeding in our cohort than predicted. Conclusions The HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had poor predictive abilities in dialysis patients. Therefore, these bleeding risk scores may not be useful in this population.

Objectives: Maintenance of independence is a challenge for nursing home residents whose pain is often substantial. The objective of this study was to explore the relationship between pain perception and care dependency in a population of Dutch nursing home residents.Design: Prospective cohort study. Setting and participants: Dutch nursing home residents aged 65 or older, excluding residents with a severe cognitive impairment.Methods: The Numeric Rating Scale (NRS) was used to rate pain perception from 0 to 10 in half-point increments and the Care Dependency Scale (CDS) to measure care dependency, with scores ranging from 15 (completely care dependent) to 75 (fully independent). Both measurements were repeated after a 2-month follow-up. Multiple linear regression analysis was used to adjust for potential confounders. Missing data were dealt with by performing tenfold multiple imputation.Results: A total of 1256 residents (65% women, mean age 83 years) were included. At baseline, the median NRS pain score was 3.0 (interquartile range 0.0-6.0) and the mean CDS score was 55.9 (SD 11.5). Cross-sectionally, for 1-point increase in pain score, care dependency increased 0.65 points [95% confidence interval (CI) 0.46-0.83]. More pain at baseline was associated with slightly lower care dependency after 2 months (beta 0.20, 95% CI 0.01-0.39). Compared with residents whose pain decreased over 2 months, residents with stable pain or increased pain had a 2.27-point (95% CI 0.83-3.70) and 2.39 point (95% CI 0.87-3.90) greater increase in care dependency, respectively.Conclusions and implications: Pain perception and care dependency are associated in a population of older nursing home residents, and stable or increased pain is associated with increased care dependency progression. The findings of this study emphasize that pain and care dependency should not be assessed nor treated independently. (C) 2020 The Author(s). Published by Elsevier Inc. on behalf of AMDA - The Society for Post-Acute and Long-Term Care Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BackgroundTo prevent bio-accumulation of low molecular weight heparins (LMWHs) in patients with decreased kidney function, dosage reduction and anti-Xa monitoring has been suggested. The aim of this study was to investigate the effect of pre-emptive dosage reduction of LMWH on anti-Xa levels. Furthermore, we investigated the association between anti-Xa levels and bleeding, thrombotic events and mortality.MethodsIn this single center study, we followed 499 patients with decreased renal function in whom anti-Xa levels were measured. We observed how many patients had anti-Xa levels that fell within the reference range, with a standard protocol of a pre-emptive dosage reduction of LMWH (25% reduction in patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73m2 and a reduction of 50% in patients with an eGFR below the 30 ml/min/1.73m2). Furthermore, Cox proportional hazard analyses were used to estimate hazard ratios to investigate the association between anti-Xa levels and major bleeding, thrombotic events and mortality within three months of follow-up.ResultsIn a cohort of 499 patients (445 dalteparin and 54 nadroparin users), a pre-emptive dosage reduction of LMWH led to adequate levels of anti-Xa in only 19% of the patients (12% for the dalteparin users and 50% for nadroparin users). We did not find an association between anti-Xa levels and bleeding, thrombosis or mortality.ConclusionPre-emptive dosage reduction of LMWH leads to low anti-Xa levels in a large proportion, but this was not associated with bleeding, thrombosis or mortality.

Background Dialysis patients have an increased bleeding risk as compared with the general population. However, there is limited information whether bleeding risks are different for patients treated with haemodialysis (HD) or peritoneal dialysis (PD). From a clinical point of view, this information could influence therapy choice. Therefore the aim of this study was to investigate the association between dialysis modality and bleeding risk. Methods Incident dialysis patients from the Netherlands Cooperative Study on the Adequacy of Dialysis were prospectively followed for major bleeding events over 3 years. Hazard ratios with 95% confidence intervals (CIs) were calculated for HD compared with PD using a time-dependent Cox regression analysis, with updates on dialysis modality. Results In total, 1745 patients started dialysis, of whom 1211 (69.4%) received HD and 534 (30.6%) PD. The bleeding rate was 60.8/1000 person-years for HD patients and 34.6/1000 person-years for PD patients. The time-dependent Cox regression analysis showed that after adjustment for age, sex, primary kidney disease, prior bleeding, cardiovascular disease, antiplatelet drug use, vitamin K antagonist use, erythropoietin use, arterial hypertension, residual glomerular filtratin rate, haemoglobin and albumin levels, bleeding risk for HD patients compared with PD increased 1.5-fold (95% CI 1.0–2.2). Conclusions In this large prospective cohort of incident dialysis patients, HD patients had an increased bleeding risk compared with PD patients. In particular, HD patients with a history of prior bleeding had an increased bleeding risk.

Aim Approximately 40% of dialysis patients are durably treated with peritoneal dialysis (PD) in our teaching hospital. Patients' perspectives were studied by patient-reported outcome measurements (PROMs) to find possible explanations for why the generally-reported decline in the use of PD hardly occurred in our facility. Materials and methods All 75 prevalent adult dialysis patients hemodialysis (HD) duration 27, PD 16 months) were included. All had received predialysis care and education for > 6 month. Cross-sectional sociodemographic and clinical data, SF-36, KDQOL-SF, and predialysis anxiety/depression scores were collected in February 2016. Differences in PROMs between PD and HD patients were analyzed. Results Despite more comorbidity in the PD population, generally-used dialysis parameters were adequate and similar between HD (n = 42) and PD (n = 33) patients as was annual mortality. Many factors associated with a predialysis modality choice for PD were absent. A higher anxiety/depression score was found in pre-HD compared to pre-PD patients. PROMs were returned by 97%. PD patients performed better on a number of PROMs than their HD counterparts. Conclusion This single-center cross-section with a modest number of patients but an almost 100% patient response shows that having 40% of patients on PD is possible with excellent results in terms of patient-reported outcomes. A structured patient education with attention to personal needs of patients, an adequate infrastructure for PD, and a dedicated team with ongoing patient support are key factors. Sharing best practices may help to slow down or even reverse the decline of PD, which is a pity both for patients and society. .

Background Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Methods Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. Results A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) −4.07 (−6.37 to −1.78) and −2.40 (−3.78 to −1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50–4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Conclusions Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

Item does not contain fulltext OBJECTIVE: To answer the dilemma clinician's face when deciding between cochlear implant (CI) and auditory brainstem implant (ABI) treatment options in patients with cochlear nerve deficiency (CND). STUDY DESIGN: Case study supplemented with literature review and meta-analysis. SETTING: Tertiary referral center. PATIENT(S): Child with CHARGE syndrome and congenital deafness. INTERVENTION(S): ABI as there was no benefit after bilateral cochlear implantation. MAIN OUTCOME MEASURES: Speech and language development, quality of life. RESULTS: In one ear the cochleovestibular nerve was present on magnetic resonance imaging (MRI) without preoperative ABR responses. In the contra lateral ear the nerve could not be identified, despite present ABR responses. Nevertheless, there was no positive outcome with CI. The patient had improved speech and language and quality of life with ABI. Of the 108 patients with CND and CI identified in the literature review, 25% attained open-set speech perception, 34% attained closed-set speech perception, and 41% detected sounds or less. The appearance of the cochlear nerve on MRI was a useful predictor of success, with cochlear nerve aplasia on MRI associated with a smaller chance of a positive outcome post cochlear implantation compared with patients with cochlear nerve hypoplasia. CONCLUSION: Although patients with (apparent) cochlear nerve aplasia are less likely to benefit from CI, CI before ABI is supported as some patients attain closed or open-set levels of speech perception after cochlear implantation.

Objective: Possibly, different biochemical parameters are involved in the development of depressive symptoms in white and non-white dialysis patients. We examined whether the association between inflammation and depressive symptoms and between tryptophan and depressive symptoms differs between white and non-white dialysis patients and whether the association between inflammation and depressive symptoms is mediated by tryptophan degradation along the kynurenine pathway in both groups.Method: Depressive symptoms were measured with the BDI-II. HsCRP, IL-1 beta, IL-6, IL-10, and TNF alpha and tryptophan and its degradation products kynurenine and 3-hydroxykynurenine were measured in 270 white and 220 non-white patients.Results: The presence of depressive symptoms was significantly higher in non-white patients (51%) than in white patients (37%) (P Conclusion: Our results indicate that for white and non-white dialysis patients different biochemical parameters are associated with depressive symptoms.

Due to continuing migration there is more interest in the mental health status of immigrants. The aim of this study is to determine the prevalence of depressive/anxiety symptoms in immigrant and native dialysis patients, and to explore if patient characteristics can explain differences. The Beck depression inventory and the beck anxiety inventory were used. Differences between native and immigrant patients were explored using logistic regression models adjusted for patient characteristics. The prevalence of depressive symptoms was 35% for 245 native patients and 50% for 249 immigrant patients. The prevalence of anxiety symptoms was 35% for native patients and 50% for immigrant patients. In addition, the prevalence for co-morbid depressive and anxiety symptoms was 20% for native patients and 32% for immigrant patients. Crude ORs for depressive/anxiety symptoms for immigrant patients versus native patients were 1.8 (1.2–2.5) and 1.7 (1.2–2.5), respectively. After adjustment for patient characteristics ORs remained the same. Clinicians should be aware that immigrant dialysis patients are more prone to develop depressive and anxiety symptoms. Cultural factors might play a role and should therefore be assessed in future research.

ObjectiveTo identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.DesignNationwide observational cohort study.SettingNational Swedish Renal Registry of patients referred to nephrologists.ParticipantsPatients had a baseline eGFR between 10 and 20 mL/min/1.73 m2and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.Main outcome measuresThe strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m2in increments of 1 mL/min/1.73 m2. An eGFR between 6 and 7 mL/min/1.73 m2(eGFR6-7) was taken as the reference.ResultsAmong 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m2), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR15-16. Compared with dialysis initiation at eGFR6-7, initiation at eGFR15-16was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR10-14veGFR5-7) and the achieved eGFRs in IDEAL (eGFR7-10veGFR5-7), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial.ConclusionsVery early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.

Purpose: The purposes of this study were to assess the importance of perceived sodium reduction barriers among patients with chronic kidney disease (CKD) and identify associated sociodemographic, clinical, and psychosocial factors. Method: A total of 156 patients with CKD completed a questionnaire assessing sodium reduction barriers (18 self-formulated items), depressive symptoms (Beck Depression Inventory), perceived autonomy support (Modified Health Care Climate Questionnaire), and self-efficacy (Partners in Health Questionnaire). Factor analysis was used to identify barrier domains. Correlation coefficients were computed to examine relationships between barrier domains and patient characteristics. Results: Nine barrier domains were identified. Barriers perceived as important were as follows: high sodium content in products, lack of sodium feedback, lack of goal setting and discussing strategies for sodium reduction, and not experiencing CKD-related symptoms (mean scores > 3.0 on 5-point scales, ranging from 1 ‘no barrier’ to 5 ‘very important barrier’). Other barriers (knowledge, attitude, coping skills when eating out, and professional support) were rated as moderately important (rated around midpoint), and the barrier ‘intrinsic motivation’ was rated as somewhat important (mean score = 1.9). Sodium reduction barrier domains were not associated with gender and kidney function, but were associated with age, level of education, number of comorbidities, perceived autonomy support, depressive symptoms, and self-efficacy (range r = 0.17–0.35). Patients with lower self-efficacy and perceived autonomy support scores experienced most sodium reduction barriers. Conclusion: Patients with CKD experience multiple important sodium reduction barriers and could benefit from support strategies that target various sodium reduction barriers and strengthen beliefs regarding self-efficacy and autonomy support. Additionally, environmental interventions should be implemented to reduce sodium levels in processed foods.

Background: Among chronic dialysis patients, associations have been found between inflammatory markers and depressive symptoms. In this population, no studies have examined the mechanism linking the association between inflammatory markers and depressive symptoms. We examined whether the association between inflammatory markers and depressive symptoms is mediated by tryptophan (TRP) degradation along the kynurenine (KYN) pathway.Methods: The data are part of an observational, prospective cohort study in five urban dialysis centres in The Netherlands. Depressive symptoms were determined with the Beck Depression Inventory. Peripheral blood was collected before dialysis to measure inflammatory markers [high sensitivity C-reactive protein (HsCRP), interleukin (IL)-1 beta, IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha)], TRP, KYN and 3-hydroxykynurenine. The KYN/TRP ratio was used as a measure of TRP degradation. The association between inflammatory markers and depressive symptoms was determined using linear regression analysis and adjusted for the KYN/TRP ratio.Results: In total, 490 chronic dialysis patients were included. HsCRP [beta= 3.8; confidence interval (CI): 1.0-6.6], IL-6 (beta= 9.1; CI: 4.0-14.1) and TNF-alpha (beta= 1.3; CI: 0.9-1.7) were associated with the KYN/TRP ratio. We found significant associations between HsCRP (beta= 0.8; CI: 0.3-1.3) and IL-6 (beta= 1.2; CI: 0.3-2.2) levels and depressive symptoms. However, this association was not attenuated after adjustment for the KYN/TRP ratio. Also, no significant associations were found between the KYN/TRP ratio and depressive symptoms.Conclusion: The association between inflammatory markers and depressive symptoms in chronic dialysis patients was not mediated by TRP degradation along the KYN pathway.

Background Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous results. No studies have investigated the interplay between ethnicity and depressive symptoms on clinical outcome in this patient population. This study aims to examine interaction between ethnicity and depressive symptoms on hospitalization and mortality in dialysis patients. Methods A multi-ethnic cohort in 10 dialysis centers included 687 dialysis patients between 2012 and 2017, with an average follow-up of 3.2 years. Depressive symptoms were measured using the Beck Depression Inventory. Interaction was assessed by investigating excess risk on an additive scale using both absolute rates and relative risks. Multivariable regression models included demographic, social, and clinical variables. Results Adverse outcomes are more pronounced in native patients, compared to immigrant patients. The risk for mortality and hospitalization is considerably higher in native patients compared to immigrants. An excess risk on an additive scale indicates the presence of possible causal interaction. Conclusions Depressive symptoms are a risk factor for hospitalization and mortality, especially in native dialysis patients. Adverse clinical events associated with depressive symptoms differ among ethnic groups. This differential association could play a role in the conflicting findings in literature. Ethnicity is an important factor when investigating depressive symptoms and clinical outcome in dialysis patients. Future research should focus on the possible mechanisms and pathways involved in these differential associations. Electronic supplementary material The online version of this article (10.1007/s40615-019-00600-0) contains supplementary material, which is available to authorized users.

BACKGROUND AND OBJECTIVES: Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007–2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment. RESULTS: In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases 10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes.

Background Patient-reported outcome measures (PROMs) are becoming increasingly important in healthcare. In nephrology, there is no agreement on which chronic kidney disease (CKD) symptom questionnaire to use. Therefore, the aim of this study is to select a valid symptom questionnaire for routine assessment in patients with advanced CKD. Methods A four-phase mixed methods approach, using qualitative and quantitative research methods, was applied. First, a systematic literature search was conducted to retrieve existing symptom questionnaires. Second, a symptom list was created including all symptoms in existing questionnaires and symptoms mentioned in interviews with patients with CKD, from which symptom clusters were identified. Next, questionnaires were selected based on predefined criteria regarding content validity. Last, two online feedback panels of patients with CKD (n = 151) and experts (n = 6) reviewed the most promising questionnaires. Results The literature search identified 121 questionnaires, of which 28 were potentially suitable for symptom assessment in patients with advanced CKD. 101 unique symptoms and 10 symptom clusters were distinguished. Based on predefined criteria, the Dialysis Symptom Index (DSI) and Palliative Care Outcome Scale-Renal Version (IPOS-Renal) were selected and reviewed by feedback panels. Patients needed 5.4 and 7.5 min to complete the DSI and IPOS-Renal, respectively (p

Background Population-specific consensus documents recommend that the diagnosis of hypertension in haemodialysis patients be based on 48-h ambulatory blood pressure (ABP) monitoring. However, until now there is just one study in the USA on the prevalence of hypertension in haemodialysis patients by 44-h recordings. Since there is a knowledge gap on the problem in European countries, we reassessed the problem in the European Cardiovascular and Renal Medicine working group Registry of the European Renal Association-European Dialysis and Transplant Association. Methods A total of 396 haemodialysis patients underwent 48-h ABP monitoring during a regular haemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-haemodialysis blood pressure (BP) ≥140/90 mmHg or use of antihypertensive agents and (ii) ABP ≥130/80 mmHg or use of antihypertensive agents. Results The prevalence of hypertension by 48-h ABP monitoring was very high (84.3%) and close to that by pre-haemodialysis BP (89.4%) but the agreement of the two techniques was not of the same magnitude (κ statistics = 0.648; P Conclusions The prevalence of hypertension in haemodialysis patients assessed by 48-h ABP monitoring is very high. Pre-haemodialysis BP poorly reflects the 48 h-ABP burden. About a third of the haemodialysis population has white coat or masked hypertension. These findings add weight to consensus documents supporting the use of ABP monitoring for proper hypertension diagnosis and treatment in this population.

ObjectivesThe medical field is facing a physician–scientist shortage. Medical schools could contribute to developing physician–scientists by stimulating student involvement in research. Studies have examined motivation for research as a key parameter of success. However, previous studies did not investigate if students act on their self-reported motivation. The aim of this study is to examine if motivation for research of medical students is related to actual research involvement. Furthermore, this study distinguishes intrinsic (IM) and extrinsic motivation (EM) for research and aims to investigate if a type of motivation matters in the relation between research motivation and involvement.Design and settingProspective cohort study in which students were surveyed at the start of medical school and reported IM and EM for research, self-efficacy, perceptions of research and curiosity on a 7-point Likert scale. One year later, students involved in research were identified. Logistic regression was used to examine influences of IM and EM on research involvement.ParticipantsAll undergraduate medical students starting at one medical school in the Netherlands in 2016. In total, 315 out of 316 students participated (99.7%), of whom 55 became involved in research (17.5%).Main outcome measureResearch involvement, which was operationalised as the enrolment of students in the research-based honours programme or the involvement of students in voluntary research activities outside of the regular curriculum.ResultsStudents with higher levels of IM were more often involved in research (OR 3.4; 95% CI 2.08 to 5.61), also after adjusting for gender, age, extracurricular high school activities, self-efficacy, perceptions and curiosity (OR 2.5; 95% CI 1.35 to 4.78). Higher levels of EM increased the odds of research involvement (OR 1.4; 95% CI 0.96 to 2.11). However, the effect of EM disappeared after adjusting for the above-mentioned factors (OR 1.05; 95% CI 0.67 to 1.63). Furthermore, the effect of IM remained after adjusting for EM, whereas the effect of EM disappeared after adjusting for IM.ConclusionsOur findings suggest that the type of motivation matters and IM influences research involvement. Therefore, IM could be targeted to stimulate research involvement and could be seen as the first step towards success in fostering the physician–scientist workforce.

Rationale & Objective Anxiety symptoms are common in dialysis patients and have a large impact on quality of life. The association of anxiety symptoms with adverse clinical outcomes in dialysis patients is largely unknown. This study examined the association of anxiety symptoms with hospitalization and mortality in patients receiving maintenance dialysis. Study Design Prospective cohort study. Setting & Participants Maintenance dialysis patients treated at 10 dialysis centers in the Netherlands between 2012 and 2016. Exposures Time-varying symptoms of anxiety and depression using the Beck Anxiety Inventory and Beck Depression Inventory. Outcomes All-cause mortality, 1-year hospitalization rate, and hospital length of stay. Analytical Approach Cox proportional hazards and Poisson regression models adjusted for sociodemographic and clinical variables. Sensitivity analyses included multiple imputation of missing data and restriction to incident patients only. Results 687 patients were included, composed of 433 prevalent and 242 incident dialysis patients. Median follow-up time was 3.1 (IQR, 3.0-3.5) years, during which 172 deaths occurred. 22% of patients had anxiety symptoms and 42% had depressive symptoms. Anxiety symptoms were associated with all-cause mortality and 1-year hospitalization rate and length of stay in all multivariable models. Anxiety symptoms showed a clear dose-response relationship with mortality. Limitations Depression and anxiety often coexist and share symptoms. The observational design of this study limits inferences about causal mechanisms between anxiety and clinical outcomes. Conclusions Anxiety symptoms are independently associated with increased risk for mortality and 1-year hospitalization. Anxiety symptoms are a clinically relevant risk factor for morbidity and mortality in dialysis patients and warrant further research on effective treatment.

Background: The educational beliefs of medical academics influence how they act in class and thus influence student learning. One component of these are beliefs academics hold about the qualities of teachers themselves. These teacher qualities range from behaviours and competencies to more personal attributes such as the teacher's identity and mission. However, it is unclear what medical academics believe to be key teacher qualities. Therefore, this study explored the variety of medical academics' beliefs about 'teacher qualities', aiming to identify and characterise profiles of academics with similar beliefs.Methods: We interviewed 26 expert academics from two medical schools to explore their beliefs about teacher qualities. A concentric onion-model focusing on teacher qualities was used to analyse and categorise the data deductively. Within each theme we developed subthemes inductively. To gain insight into the variety of beliefs we then clustered the participants into teacher profiles according to the themes. To better understand each of the profiles we carried out a quantitative study of the differences between profiles regarding subthemes, contextual and personal factors, and analysed statistical significance using Fisher's exact- and Student's t-tests for categorical and continuous data, respectively.Results: Four profiles of medical academics were identified, corresponding to the most central theme that each participant had reflected on: the 'Inspirer', 'Role-model', 'Practitioner', and 'Critic'. The focus of the profiles varied from external constraining factors within the 'Critic' profile to affective personal qualities within the 'Role-model' and 'Inspirer' profiles. The profiles could be regarded as hierarchically ordered by inclusiveness. Educational institute was the only significant factor related to the profiles.Conclusions: Besides the relevance of affective teacher qualities, the 'Inspirer' profile demonstrates the importance of developing a clear mission as a teaching academic, centred around student learning and professional development. In our view, academics who inspire their students continue to be inspired themselves.The practical implications are described for faculty development programmes, and for the potential value of using these profiles within medical schools. In the discourse on educational beliefs, the authors argue that more attention should be paid to affective qualities, in particular to explicating the educational mission of academics.

For immigrant chronic dialysis patients, religious behavior and religious coping may have a different impact on depressive symptoms compared to native patients. This study aims to describe both cross-sectional and longitudinal associations between religious behavior and coping with symptoms of depression for 281 native and 277 immigrant dialysis patients in the Netherlands. A higher prevalence of depressive symptoms was found in immigrant compared to native patients (49% vs. 36%). No significant cross-sectional or longitudinal associations were found in both groups between religious behavior and positive religious coping with depressive symptoms. Strong significant cross-sectional associations were found between negative religious coping items and depressive symptoms in both groups, while no longitudinal associations were found. So, similar impact of religiousness on the presence of depressive symptoms was found for both native and immigrant dialysis patients. Therefore, these results do not explain the higher prevalence of depressive symptoms found in immigrant chronic dialysis patients compared to native patients.

Objective: Patients undergoing chronic dialysis often display sustained elevations of inflammation markers and also have a high prevalence of depressive symptoms. Although multiple studies demonstrated cross-sectional associations between inflammation markers and depressive symptoms in this patient group, longitudinal associations have not been examined. We therefore investigated whether longitudinal associations exist between inflammation markers and depressive symptoms in chronic dialysis patients.Methods: Data of three consecutive measurements of an observational, prospective cohort study among chronic dialysis patients were used. At baseline, 6-month, and 12-month follow-up, patients completed the Beck Depression Inventory, and inflammation markers (high-sensitivity C-reactive protein [HsCRP], interleukin (IL)-1 beta, IL-6, IL-10, and tumor necrosis factor a) were measured. We examined cross-sectional associations between inflammation markers and depressive symptoms using linear regression models. The longitudinal association between inflammation and depressive symptoms was assessed using a linear mixed model analyses.Results: A total of 513 patients were included. Cross-sectional associations were found between HsCRP and depressive symptoms at baseline (beta = 0.9, confidence interval [CI] = 0.4-1.4) and 6-month follow-up (beta = 1.1, CI = 0.3-2.0), and between IL-1 beta and depressive symptoms at 6-month follow-up (beta = 1.3, CI = 0.8-1.8) and 12-month follow-up (beta = 1.2, CI = 0.4-1.9). Inflammation makers (HsCRP, IL-6, IL-1 beta, IL-10, and tumor necrosis factor a) at baseline were not associated with depressive symptoms at follow-up and vice versa.Conclusions: We confirmed the presence of cross-sectional associations between inflammation markers and depressive symptoms in chronic dialysis patients, but with our longitudinal data, we found no longitudinal associations. This supports an associative instead of a causal relationship between inflammation and depressive symptoms.

Background An easy to use prediction model for long-term renal patient survival, based on only four predictors (age, primary renal disease, sex, and therapy at 90 days after the start of renal replacement therapy (RRT)), has been developed in the Netherlands. To assess the usability of this model for use in Europe, we externally validated the model in ten European countries. Methods Data from the ERA-EDTA (European Renal Association - European Dialysis and Transplant Association) Registry were used. Ten countries that reported individual patient data to the registry on patients starting RRT in the period of 1995-2005 were included. Patients under 16 years of age and/or with missing predictor variable data were excluded. The external validation of the prediction model was evaluated for the 10-year (primary endpoint), 5- and 3-year survival predictions by assessing the calibration and discrimination outcomes. Results We used a dataset of 136,304 patients from 10 countries. The calibration in the large and calibration plots for 10 deciles of predicted survival probabilities showed average differences of 1.5%, 3.2% and 3.4% in observed versus predicted 10-, 5-, and 3-year survival, with some small variation on country-level. The C-index, indicating the discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry cohort and varied according to country level between 0.70 and 0.75. Conclusions A prediction model for long-term renal patient survival developed in a single country, based on only four easily available variables, has a comparably adequate performance in a wide range of other European countries.

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.

Introduction The medical field is currently facing a physician-scientist shortage. One possible solution is to direct medical students towards a research oriented career. To do so, knowledge is needed on how to motivate medical students to do research. Therefore, this study examines motivation for research and identifies factors influencing intrinsic and extrinsic motivation for research among first-year medical students. Methods First-year medical students were surveyed at the beginning of their bachelor’s program in 2016. On a 7-point Likert scale, students reported their motivation for research, self-efficacy, perceptions of research, curiosity, and need for challenge. Regression analyses were used to examine the influence of these factors on students’ motivation for research. Results Out of 316 approached students, 315 participated (99.7%). On average, students scored 5.49 on intrinsic, and 5.66 on extrinsic motivation for research. All factors measured influenced intrinsic and extrinsic motivation for research significantly and positively, also after adjusting for gender and age. Cumulative regression showed that these factors explained 39.6% of the variance in intrinsic, and 14% in extrinsic motivation for research. Discussion All factors play an important role in intrinsic and, to a lesser extent, extrinsic motivation for research. First-year medical students’ motivation for research could be enhanced by stimulating positive self-efficacy beliefs, positive perceptions of research, and curiosity. Also, it is important to fulfil students’ needs for challenge by stimulating them to actively conduct research. Thus, to catch students young and cultivate physician-scientists, students should be stimulated to engage in research from the beginning of medical training.

Objectives: Prevalence and risk factors for protein-energy wasting (PEW) are poorly studied in the nondialysis, older population with advanced chronic kidney disease (CKD). Our aim was to evaluate the prevalence of PEW in advanced stage CKD patients aged greater than 65 years. Furthermore, we aimed to describe risk factors for PEW in the overall study population and among obese individuals. Design: Prospective observational cohort study. Methods: The EQUAL study, a European Quality Study on treatment in advanced chronic kidney disease, is a multicenter prospective observational cohort study in six European countries. We included patients aged ≥65 years with incident glomerular filtration rate 2 not on dialysis attending nephrology care. PEW was assessed by 7-point Subjective Global Assessment (7-p SGA). Results: In general, the study cohort (n = 1,334) was overweight (mean body mass index [BMI] 28.4 kg/m2). The majority of the patients had a normal nutritional status (SGA 6-7), 26% had moderate PEW (SGA 3-5), and less than 1% had severe PEW (SGA 1-2). Muscle wasting and loss of fat tissue were the most frequent alterations according to the SGA subscales, especially in those aged >80 years. The prevalence of PEW was higher among women, increased with age, and was higher in those with depression/dementia. PEW was the most common in those with underweight (BMI 2), 55% or normal weight (BMI 22-25 kg/m2), 40%. In obese individuals (BMI >30 kg/m2), 25% were diagnosed with protein wasting. Risk factors for SGA ≤5 in obese people were similar to those for the overall study population. Conclusion: This European multicenter study shows that the prevalence of PEW is high in patients with advanced CKD aged >65 years. The risk of PEW increases substantially with age and is commonly characterized by muscle wasting. Our study suggests that focus on nutrition should start early in the follow-up of older adults with CKD.

Disturbances in calcium metabolism are common in individuals with chronic kidney disease (CKD), but whether they are associated with subsequent kidney function decline is less clear. In a CKD 3–5 cohort of 15,755 adult citizens of Stockholm with creatinine tests taken during 2006–2011 and concurrent calcium testing at cohort entry, we investigated the association between baseline serum calcium and the subsequent change in estimated glomerular filtration rate (eGFR, by CKD-EPI) decline using linear mixed models. Mean (SD) baseline corrected serum calcium was 9.6 (0.5) mg/dL. Mean (95%-confidence interval [CI]) eGFR decline was −0.82 (−0.90; −0.74) mL/min/1.73 m2/year. In advanced CKD stages, higher baseline serum calcium was associated with less rapid kidney function decline. The adjusted change (95%-CI) in eGFR decline associated with each mg/dL increase in baseline serum calcium was −0.10 (−0.28; 0.26), 0.39 (0.07; 0.71), 0.34 (−0.02; 0.70) and 0.68 (0.36; 1.00) mL/min/1.73 m2/year for individuals in CKD stage 3a, 3b, 4, and 5, respectively. In a subgroup of patients using vitamin D supplements, the association between baseline serum calcium and CKD progression was eliminated, especially in CKD stage 3b and 4. To conclude, in individuals with CKD stage 3b to 5, lower baseline corrected serum calcium, rather than higher baseline serum calcium, associated with a more rapid CKD progression. Lower serum corrected calcium seems to be indicative for vitamin D deficiency.

Objective To examine the prevalence of and risk factors for malnutrition at the start of specialized predialysis care. Design The present analysis was performed on cross-sectional data collected at inclusion in the study. The study included 25 outpatient clinics delivering specialized predialysis care in the Netherlands. Subjects Three hundred seventy-six incident patients with advanced chronic kidney disease attending one of the participating outpatient clinics. Main Outcome Measure Subjective global assessment (SGA) of nutritional status. Results At the start of specialized predialysis care, 11% of patients suffer from moderate protein–energy wasting as measured by SGA. Independent risk factors are age >75 years (Odds ratio [OR], 3.88 [1.74-8.66]), female gender (OR, 2.95 [1.37-6.32]), and having a body mass index 2 (OR, 2.56 [1.19-5.49]). Estimated glomerular filtration rate was not significantly associated with SGA (OR, 1.63 [0.76-3.48]). Conclusions Eleven percent of patients started on specialized predialysis care suffer from moderate protein–energy wasting; risk factors are age >75 years, female gender, and BMI 2 .

Purpose: Type D personality has been identified as an independent risk factor for survival in cardiovascular disease (CVD) patients. As CVD is present in about 50% of dialysis patients, it is of clinical interest to assess the prevalence of type D personality, the association with depressive and anxiety symptoms, and stability of type D personality in dialysis patients. Methods: Data was used from two consecutive measurements of the DIVERS study, a prospective cohort study among chronic dialysis patients in the Netherlands. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and the Type D Scale-14 (DS14) were used to assess depressive and anxiety symptoms and type D personality, respectively. The association of type D personality was assessed with analysis of variance F test. Stability of type D personality, depressive, and anxiety symptoms were determined by calculating Cohen’s κ, and by determining the positive agreement. Results: In total, 349 patients were included of which 249 patients had two measurement points. The prevalence of type D personality was 21% and type D personality was associated with depressive and anxiety symptoms (P

Background Obesity increases risk of hypertension and diabetes, the leading causes of end-stage renal disease. The effect of obesity on kidney function decline in stable post-myocardial infarction patients is poorly documented. This relation was investigated in a large cohort of older post-myocardial infarction patients. Design Data were analysed from 2410 post-myocardial infarction patients in the Alpha Omega Trial, aged 60–80 years receiving optimal pharmacotherapy treatment (79% men, 18% diabetes). Methods Cystatin C based estimated glomerular filtration rate (eGFRcysC) was calculated at baseline and after 41 months, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Obesity was defined as body mass index ≥ 30 kg/m2 and high waist circumference as ≥102 and ≥88 cm for men and women. The relation between body mass index, waist circumference and annual eGFRcysC decline was evaluated by linear regression. Results At baseline, mean (standard deviation) eGFRcysC was 81.5 (19.6) ml/min/1.73 m2, 23% of all patients were obese. After multivariable adjustment, the annual mean (95% confidence interval) eGFRcysC decline in men and women was –1.45 (–1.59 to –1.31) and –0.92 (–1.20 to –0.63) ml/min/1.73 m2, respectively ( p = 0.001). Obese versus non-obese patients and patients with high versus normal waist circumference experienced greater annual eGFRcysC decline. Men and women showed an additional annual eGFRcysC decline of –0.35 (–0.56 to –0.14) and –0.21 (–0.55 to 0.14) ml/min/1.73 m2 per 5 kg/m2 body mass index increment ( p for interaction 0.3). Conclusions High compared to normal body mass index or waist circumference were associated with more rapid kidney function decline in older stable post-myocardial infarction patients receiving optimal drug therapy.

Background. The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc scores in a cohort of end-stage renal disease patients receiving dialysis treatment. Methods. We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and causespecific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use. Results. Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0-1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6-4.0) increased stroke mortality risk, a 1.3-fold (95% CI 0.4-4.2) increased bleeding mortality risk, a 1.2-fold (95% CI 0.9-1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8-1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score 1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0-7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score 2 was not associated with an increasedmortality risk after adjustment. Conclusion. Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication.

Objectives Illness perceptions in patients with end-stage renal disease are associated with nonadherence and increased mortality. However, no data are available regarding the relationship between illness perceptions and accelerated disease progression in predialysis patients. Methods A total of 416 incident predialysis patients participating in a prospective cohort (PREPARE-2, Predialysis Patient Record-2) completed the Revised Illness Perception Questionnaire at the start of specialized predialysis care. The association between illness perceptions and time until start of dialysis was investigated using Cox regression models. Linear mixed modeling was used to test associations between illness perceptions and change of kidney function during predialysis care. Adjustments were made for sociodemographic, clinical, and biochemical factors. Results Five illness perceptions were associated with disease progression. Dialysis started earlier and kidney function declined faster (ml/min per 1.73 m/y) in patients who perceived their kidney disease as being cyclical in nature (adjusted hazard ratio [HRadj] = 1.32 [95% confidence interval {CI} = 1.11-1.56]; adjusted additional change = -0.64 [95% CI = -1.16 to -0.13]), having many negative consequences (HRadj = 1.47 [95% CI = 1.18-1.85]; adjusted additional change = -0.67 [-1.30 to -0.04]) and causing negative feelings (HRadj = 1.21 [95% CI = 1.03-1.42]; adjusted additional change = -0.65 [95% CI = -1.13 to -0.16]). In addition, kidney function declined faster in patients who perceived that their kidney disease cannot be personally controlled (adjusted additional change = -0.69 [95% CI = -1.31 to -0.09]) and who perceived that they did not fully understand their kidney disease (adjusted additional change = -0.53 [-1.05 to -0.01]). Conclusions Stronger negative perceptions of illness at the start of predialysis care are a marker for accelerated disease progression. Detecting illness perceptions in predialysis patients may provide opportunities to intervene and slow down disease progression.

Since the introduction of the bivalent human papilloma virus (HPV) vaccine in the Netherlands, migraine has been reported as a notable event in the passive safety surveillance system. Research on the association between HPV vaccination and migraine is needed. Therefore, potential migraine cases in 2008–2010 were selected from a group of general practitioners and linked to the vaccination registry. Data were analysed in three ways: (i) incidences of migraine postvaccination (2009/2010) were compared to pre-vaccination incidences (2008); (ii) in a cohort, incidence rates of migraine in vaccinated and unvaccinated girls were compared and (iii) in a self-controlled case series analysis, the relative incidence of migraine in potentially high-risk periods was compared to non-high-risk periods. Incidence rates of migraine for 12- to 16-year-old girls and boys postvaccination were slightly higher than pre-vaccination incidence rates. Incidence rate ratios (IRRs) for vaccinated compared to unvaccinated girls were not statistically significantly higher. Furthermore, the RR for migraine in the high-risk period of 6 weeks following each dose versus non-high-risk period was 4.3 (95% confidence interval (CI) 0.69–26.6) for certain migraine. Conclusion: Using different methods, no statistically significant association between HPV vaccination and incident migraine was found. However, the number of cases was low; to definitively exclude the risk, an increased sample size is needed.

Objective: To identify health-related quality of life (HRQOL) trajectories during 18 months of predialysis care and associated patient characteristics and illness perceptions. Method: 396 incident predialysis patients participating in the prospective PREdialysis PAtient REcord-2 study completed every 6 months the 36-item Short Form Health Survey (i.e., mental and physical HRQOL) and Revised Illness Perception Questionnaire. HRQOL trajectories were examined using latent class growth models, and associated baseline factors were identified using logistic regression. Analyses for illness perceptions were adjusted for demographic and clinical characteristics. Results: Three physical HRQOL trajectories (low-stable [34.1% of the sample], medium-declining [32.5%], and high-increasing [33.4%]) and two mental HRQOL trajectories (low-stable [38.7%] and high-stable [61.3%]) were identified. Increased odds for a low-stable physical HRQOL trajectory were detected in older patients (Odds ratio [OR] = 1.04), patients with cardiovascular disease (OR = 2.1) and patients who believed to a lesser extent they can personally control their disease (ORadj = 0.88). Increased odds for both a low-stable physical and mental HRQOL trajectory were detected in patients who believed to a higher extent that their disease is cyclical, has negative consequences, causes negative feelings, and in patients who believed to a lesser extent they understand their disease (ORadj ranged between 0.84 and 1.36). Additionally, patients who attributed more symptoms to their disease had increased odds for a medium-declining (ORadj = 1.21) and low-stable physical HRQOL trajectory (ORadj = 1.50). Conclusions: Older age and cardiovascular disease are markers for unfavorable physical HRQOL trajectories, and stronger negative illness perceptions are markers for unfavorable physical and mental HRQOL trajectories. Targeting negative illness perceptions could possibly optimize HRQOL during predialysis care. (PsycINFO Database Record

Research integrated into undergraduate education is important in order for medical students to understand and value research for later clinical practice. Therefore, attempts are being made to strengthen the integration of research into teaching from the first year onwards. First-year students may interpret attempts made to strengthen research integration differently than intended by teachers. This might be explained by student beliefs about learning and research as well as student perceptions of the learning environment. In general, student perceptions of the learning environment play a pivotal role in fostering student learning outcomes. This study aims to determine whether a curriculum change intended to promote research integration fosters student learning outcomes and student perceptions of research integrated into teaching. To serve this purpose, three subsequent cohorts of first-year students were compared, one before and two after a curriculum change. Learning outcomes of these students were measured using scores on a national progress test of 921 students and assessments of a sample of 100 research reports of a first-year student research project. 746 Students filled out the Student Perceptions of Research Integration Questionnaire. The findings suggest that learning outcomes of these students, that is, scores on research related test items of the progress test and the quality of research reports, were better than those of students before the curriculum change.

Globally the number of patients on renal replacement therapy (RRT) is rising. Dyslipidemia is a potential modifiable cardiovascular risk factor, but its effect on risk of RRT or death in pre-dialysis patients is unclear. The aim of this study was to assess the association between dyslipidemia and risk of RRT or death among patients with CKD stage 4–5 receiving specialized pre-dialysis care, an often under represented group in clinical trials. Of the 502 incident pre-dialysis patients (>18 y) in the Dutch PREPARE-2 study, lipid levels were available in 284 patients and imputed for the other patients. During follow up 376 (75%) patients started RRT and 47 (9%) patients died. Dyslipidemia was defined as total cholesterol ≥5.00 mmol/L, LDL cholesterol ≥2.50 mmol/L, HDL cholesterol

Background & Aims Proton pump inhibitors (PPI) have been associated with acute kidney injury and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD). Methods We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n = 105,305) and new users of H 2 blockers (H 2 B; n = 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury. Complete collection of repeated PPI and H 2 B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated with cumulative PPI exposure. Results Users of PPIs, compared with users of H 2 Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05–1.51) and decrease in estimated glomerular filtration rate of 30% or more (11,045 events; 1.26; 95% CI, 1.16–1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 95% CI, 0.76–7.58) and acute kidney injury (HR, 1.30; 95% CI, 1.00–1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H 2 B use. Conclusions Initiation of PPI therapy and cumulative PPI exposure is associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.

For preventive purposes it is important to be able to identify families with a high risk of child maltreatment at an early stage. Therefore we developed an actuarial instrument for screening families with a newborn baby, the Instrument for identification of Parents At Risk for child Abuse and Neglect (IPARAN). The aim of this study was to assess the predictive validity of the IPARAN and to examine whether combining actuarial and clinical methods leads to an improvement of the predictive validity. We examined the predictive validity by calculating several performance indicators (i.e., sensitivity, specificity and the Area Under the receiver operating characteristic Curve [AUC]) in a sample of 4692 Dutch families with newborns. The outcome measure was a report of child maltreatment at Child Protection Services during a follow-up of 3 years. For 17 children (.4%) a report of maltreatment was registered. The predictive validity of the IPARAN was significantly better than chance (AUC = .700, 95% CI [.567–.832]), in contrast to a low value for clinical judgement of nurses of the Youth Health Care Centers (AUC = .591, 95% CI [.422–.759]). The combination of the IPARAN and clinical judgement resulted in the highest predictive validity (AUC = .720, 95% CI [.593–.847]), however, the difference between the methods did not reach statistical significance. The good predictive validity of the IPARAN in combination with clinical judgment of the nurse enables professionals to assess risks at an early stage and to make referrals to early intervention programs.