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The availability of electronic health records and access to a large number of routine measurements of serum creatinine and urinary albumin enhance the possibilities for epidemiologic research in kidney disease. However, the frequency of health care use and laboratory testing is determined by health status and indication, imposing certain challenges when identifying patients with kidney injury or disease, when using markers of kidney function as covariates, or when evaluating kidney outcomes. Depending on the specific research question, this may influence the interpretation, generalizability, and/or validity of study results. This review illustrates the heterogeneity of working definitions of kidney disease in the scientific literature and discusses advantages and limitations of the most commonly used approaches using 3 examples. We summarize ways to identify and overcome possible biases and conclude by proposing a framework for reporting definitions of exposures and outcomes in studies of kidney disease using routinely collected health care data.

PURPOSE Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A. METHODS Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound. RESULTS Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia. CONCLUSION This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival.

Aims Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations and updates, assess their methodological quality, and calculate pooled estimates of the predictive performance. Methods and results We searched PubMed and Web of Science for studies developing, validating, or updating risk scores for IS in AF patients. Methodological quality was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). To assess discrimination, pooled c-statistics were calculated using random-effects meta-analysis. We identified 19 scores, which were validated and updated once or more in 70 and 40 studies, respectively, including 329 validations and 76 updates—nearly all on the CHA2DS2-VASc and CHADS2. Pooled c-statistics were calculated among 6 267 728 patients and 359 373 events of IS. For the CHA2DS2-VASc and CHADS2, pooled c-statistics were 0.644 [95% confidence interval (CI) 0.635–0.653] and 0.658 (0.644–0.672), respectively. Better discriminatory abilities were found in the newer risk scores, with the modified-CHADS2 demonstrating the best discrimination [c-statistic 0.715 (0.674–0.754)]. Updates were found for the CHA2DS2-VASc and CHADS2 only, showing improved discrimination. Calibration was reasonable but available for only 17 studies. The PROBAST indicated a risk of methodological bias in all studies. Conclusion Nineteen risk scores and 76 updates are available to predict IS in patients with AF. The guideline-endorsed CHA2DS2-VASc shows inferior discriminative abilities compared with newer scores. Additional external validations and data on calibration are required before considering the newer scores in clinical practice. Clinical trial registration ID CRD4202161247 (PROSPERO).

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 (

Objectives: To (1) explore trends of risk of bias (ROB) in prediction research over time following key methodological publications, using the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and (2) assess the inter-rater agreement of the PROBAST. Study Design and Setting: PubMed and Web of Science were searched for reviews with extractable PROBAST scores on domain and signaling question (SQ) level. ROB trends were visually correlated with yearly citations of key publications. Inter-rater agreement was assessed using Cohen's Kappa. Results: One hundred and thirty nine systematic reviews were included, of which 85 reviews (containing 2,477 single studies) on domain level and 54 reviews (containing 2,458 single studies) on SQ level. High ROB was prevalent, especially in the Analysis domain, and overall trends of ROB remained relatively stable over time. The inter-rater agreement was low, both on domain (Kappa 0.04–0.26) and SQ level (Kappa −0.14 to 0.49). Conclusion: Prediction model studies are at high ROB and time trends in ROB as assessed with the PROBAST remain relatively stable. These results might be explained by key publications having no influence on ROB or recency of key publications. Moreover, the trend may suffer from the low inter-rater agreement and ceiling effect of the PROBAST. The inter-rater agreement could potentially be improved by altering the PROBAST or providing training on how to apply the PROBAST.

Background Unhelpful illness perceptions can be changed by means of interventions and can lead to improved outcomes. However, little is known about illness perceptions in patients with chronic kidney disease (CKD) prior to kidney failure, and no tools exist in nephrology care to identify and support patients with unhelpful illness perceptions. Therefore, this study aims to: (1) identify meaningful and modifiable illness perceptions in patients with CKD prior to kidney failure; and (2) explore needs and requirements for identifying and supporting patients with unhelpful illness perceptions in nephrology care from patients’ and healthcare professionals’ perspectives. Methods Individual semi-structured interviews were conducted with purposive heterogeneous samples of Dutch patients with CKD (n = 17) and professionals (n = 10). Transcripts were analysed using a hybrid inductive and deductive approach: identified themes from the thematic analysis were hereafter organized according to Common-Sense Model of Self-Regulation principles. Results Illness perceptions considered most meaningful are related to the seriousness (illness identity, consequences, emotional response and illness concern) and manageability (illness coherence, personal control and treatment control) of CKD. Over time, patients developed more unhelpful seriousness-related illness perceptions and more helpful manageability-related illness perceptions, caused by: CKD diagnosis, disease progression, healthcare support and approaching kidney replacement therapy. Implementing tools to identify and discuss patients’ illness perceptions was considered important, after which support for patients with unhelpful illness perceptions should be offered. Special attention should be paid towards structurally embedding psychosocial educational support for patients and caregivers to deal with CKD-related symptoms, consequences, emotions and concerns about the future. Conclusions Several meaningful and modifiable illness perceptions do not change for the better by means of nephrology care. This underlines the need to identify and openly discuss illness perceptions and to support patients with unhelpful illness perceptions. Future studies should investigate whether implementing illness perception-based tools will indeed improve outcomes in CKD.

Background Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between symptom prevalence and burden with HRQOL, and age and gender differences in symptom experience. Methods Eligible Dutch KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. HRQOL, and occurrence and burden of 62 symptoms were measured using validated questionnaires. Univariate and multivariate regression analysis were used for investigating the associations of symptom experience with mental and physical HRQOL, and differences in symptom experience between genders and KTRs of diverse age groups. Results A total of 631 KTRs were analyzed; the mean (standard deviation) age was 61.3 (11.3) years, and 62% were male. The median (interquartile range) number of symptoms was 14 (7–22), with a burden of 20 (8–37; range 0–244). Per extra symptom, physical and mental HRQOL decreased [–0.41 (–0.50; –0.31) and –0.51 (–0.59; –0.42), respectively, P 50–65 ≥65 years) feelings of depression and both female and younger KTRs reported higher symptom prevalence concerning changes in physical appearance. Conclusion KRTs’ symptom experience differed depending on gender and age, highlighting the need to develop tailored treatment strategies to reduce symptom experience and subsequently improve HRQOL.

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

IntroductionMultiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs) may circumvent these limitations. We investigated VSAQ reliability, discriminative capability, acceptability, and knowledge retention compared to MCQs.MethodsDutch undergraduate medical students (n=375) were randomised to a formative exam with VSAQs first and MCQs second or vice versa in two courses, to determine reliability and discrimination. Next, acceptability (i.e., VSAQ review time) was determined in the summative exam. Knowledge retention at 2 and 5 months was determined by comparing score increase on the three-monthly progress test (PT) between students tested with VSAQs and students from previous years tested without VSAQs.ResultsReliability (Cronbach’s α) was 0.74 for VSAQs and 0.57 for MCQs in one course. In the other course, Cronbach’s α was 0.87 for VSAQs and 0.83 for MCQs. Discrimination (Rir) was 0.27 vs. 0.17 and 0.43 vs. 0.39 for VSAQs vs. MCQs, respectively. Reviewing time of one VSAQ for the entire student cohort was ±2 minutes on average. No clear effect on knowledge retention after 2 and 5 months was observed.DiscussionWe found increased reliability and discrimination of VSAQs compared to MCQs. Reviewing time of VSAQs was acceptable. The association with knowledge retention was unclear in our study. This study supports and extends positive results of previous studies on VSAQs regarding reliability, discriminative capability, and acceptability in Dutch undergraduate medical students.

Background: Symptoms of anxiety are often unrecognized and untreated in dialysis patients. We investigated the diagnostic accuracy of two widely used screening tools for anxiety in hemodialysis patients. Methods: For this cross-sectional validation study, chronic hemodialysis patients from eight dialysis centers in the Netherlands were included. The Beck Anxiety Inventory (BAI) and Hospital Anxiety and Depression Scale—Anxiety subscale (HADS-A) were validated by the Mini International Neuropsychiatric Inventory (MINI) diagnostic interview. Receiver operating characteristic curves were used to determine the optimal cut-off values. Results: Of 65 participants, 13 (20%) were diagnosed with one or more anxiety disorders on the MINI, of which 5 were included in the analysis. ROC curves showed a good diagnostic accuracy of the BAI and HADS-A. The optimal cut-off value for the BAI was ≥13 (sensitivity 100%, specificity 85%) and for the HADS-A was ≥10 (sensitivity 80%, specificity 100%). Conclusions: Based on our limited data, both the BAI and the HADS-A seem to be valid screening instruments for anxiety in hemodialysis patients that can be used in routine dialysis care. The HADS-A consists of fewer items and showed fewer false-positive results than the BAI, which might make it more useful in clinical practice.

BACKGROUND AND AIMS In the general population, men have a higher risk of major adverse cardiovascular events (MACE) compared with women, with this risk difference between men and women decreasing with increasing age. Patients with chronic kidney disease (CKD) are at a higher risk of MACE compared with the general population, but sex differences in this group, especially older adults, are not fully known. We aim to identify differences in the risk of (recurrent) MACE by sex in CKD patients over 65 years old from Europe and explore factors that may explain these differences. METHOD The European Quality study (EQUAL study) is a prospective study on stage 4–5 CKD patients not on dialysis from Germany, Italy, Poland, Sweden, the UK and the Netherlands who were ≥ 65 years old. Cox regression and cumulative incidence competing risk curves were used to calculate MACE risks. Mediation analysis was used to identify variables that may explain risk differences between men and women. RESULTS In 1136 men and 607 women, over a follow-up period of 5 years, 417 (37%) men and 185 (31%) women experienced at least one MACE, and there was a total of 1247 MACE. Men and women had 123 (14% of total MACE in men) and 54 (14% of total MACE in women) fatal MACE, respectively. The most common type of first MACE was peripheral vascular disease for men and congestive heart failure for women (Fig. 1). Accounting for the competing risk of non-MACE death, the probability of having a first MACE was 43% (95% CI: 40–47%) for men and 39% (95% CI: 34–44%) for women (Fig. 2), corresponding with a 18% lower relative risk of first MACE in women (HR: 0.82; 95% CI: 0.69–0.97; P = 0.02 ). There was no significant difference in the risk of recurrent MACE (HR: 0.91; 95% CI: 0.80–1.03; P = 0.14 ) or fatal MACE (HR: 0.84; 95% CI: 0.61–1.16; P = 0.30) between men and women. Adjusting for pre-existing comorbidities attenuated the MACE risk difference between men and women. MACE risk differences between men and women changed according to age group but not according to diabetes status. In those ≤ 75 years, women had a 25% lower risk of first MACE (HR: 0.75; 95% CI: 0.57–0.99; P = 0.04), which was 15% in those > 75 years old (HR: 0.85; 95% CI: 0.68–1.06; P = 0.14 ). The risk difference of fatal MACE between men and women differed greatly between those ≤ 75 years old (HR: 1.38; 95% CI: 0.82–2.33; P = 0.22 ) and those > 75 years (HR: 0.61; 95% CI: 0.41–0.93; P = 0.02). CONCLUSION Men had a higher probability of having a MACE over a 5-year period. Overall, women had lower risks of MACE compared with men, but risk differences between men and women changed with increasing age. Pre-existing comorbidities explained part of this risk difference.

BACKGROUND AND AIMS The risk–benefit ratio of continuing with renin–angiotensin system inhibitors (RASi) after an episode of acute kidney injury (AKI) is unclear. While stopping RASi may prevent recurrent AKI or hyperkalaemia, it may deprive patients of the cardiovascular benefits of using RASi. METHOD We analysed outcomes of long-term RASi users experiencing AKI (stage 2 or 3, or clinically coded) during hospitalization in Stockholm, Sweden, during 2007–2018. We compared stopping RASi within 3 months after discharge with continuing. The primary study outcome was the composite of all-cause mortality, myocardial infarction and stroke. Recurrent AKI was our secondary outcome, and we considered hyperkalaemia as a positive control outcome. Propensity score overlap weighted Cox models were used to estimate hazard ratios, balancing 75 confounders. Weighted absolute risk differences (ARD) were also determined. RESULTS We included 10 165 individuals, of whom 4429 stopped and 5736 continued RASi, with a median follow-up of 2.3 years. Median age was 78 years, 45% were women, and median kidney function before the index episode of AKI was 55 mL/min/1.73 m2. After weighting, those who stopped had an increased risk [HR, 95% confidence interval (95% CI)] of the composite of death, myocardial infarction and stroke (1.13, 1.07–1.19; ARD 3.7, 95% CI 2.6–4.8) compared with those who continued, a similar risk of recurrent AKI (0.94, 0.84–1.05), and a decreased risk of hyperkalaemia (0.79, 0.71–0.88). CONCLUSION Stopping RASi use among survivors of moderate-to-severe AKI was associated with a similar risk of recurrent AKI, but higher risk of the composite of death, myocardial infarction and stroke.

Background: Differences in symptom burden, treatment satisfaction and autonomy between patients receiving peritoneal dialysis and haemodialysis could be reflected by a difference in symptom dimensions of anxiety and depression. The aim of this study is to assess differences in prevalence and symptom dimensions of anxiety and depression between patients receiving peritoneal dialysis and haemodialysis. Methods: Baseline data from the Depression Related Factors and Outcomes in Dialysis Patients With Various Ethnicities and Races Study were used. Symptoms of anxiety and depression were measured with the Beck Anxiety Inventory and Beck Depression Inventory– second edition. Linear and logistic regression models were used to compare anxiety and depression total scores and somatic and subjective/cognitive symptom dimension scores between patients receiving peritoneal dialysis and haemodialysis, adjusted for potential confounders. Results: In total, 84 patients receiving peritoneal dialysis and 601 patients receiving haemodialysis were included. Clinically significant symptoms of anxiety and depression were present in respectively 22% and 43% of the patients, with no differences between dialysis modality. Both modalities scored high on the somatic symptom dimensions and on individual somatic items. Almost all patients reported symptoms related to loss of energy and sleep. Conclusion: No differences in symptom dimensions of anxiety and depression were found between patients receiving peritoneal dialysis and haemodialysis. The high prevalence of somatic symptom dimensions in both groups underscores the possible interaction between somatic and psychiatric symptoms in dialysis patients and the need for early recognition and treatment of symptoms of anxiety and depression regardless of treatment modalities.

BACKGROUND AND AIMS The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently developed a novel creatinine-based eGFR equation without a race coefficient. While American nephrology societies recommend using this novel equation, its implications are unknown. METHOD We included 1.6 million adult individuals with routine outpatient serum creatinine testing during 2007–2018 in Stockholm, Sweden. First, we calculated reclassification across KDIGO eGFR categories when changing from the 2009 to 2021 CKD-EPI equation. Second, for both equations, the association between eGFR and (1) kidney failure with replacement therapy (KFRT), (2) all-cause mortality, (3) cardiovascular mortality and (4) major adverse cardiovascular events was estimated with Cox regression. Third, prognostic accuracy of both eGFR equations within the Kidney Failure Risk Equation was assessed with discrimination and calibration. RESULTS Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median (IQR) of 3.9 (2.9–4.8) mL/min/1.73 m2, decreasing prevalence of CKD G3–G5 from 5.1 to 3.8%. The 2021 equation reclassified 9.9% of the total population and 36.2% of the CKD G3–G5 population to a less severe eGFR category. Individuals who were reclassified to less severe eGFR categories were older and therefore exhibited higher crude risks of all-cause/cardiovascular death and major adverse cardiovascular events, and lower risk of kidney replacement therapy compared with nonreclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with similar discrimination and calibration for the Kidney Failure Risk Equation. CONCLUSION Implementing the 2021 CKD-EPI equation in predominantly white European populations raises eGFR by a modest amount (larger at older age and men) and shifts a major proportion of CKD patients to a higher eGFR category, with eGFR by both equations strongly predicting outcomes.

BACKGROUND AND AIMS In older people with end-stage kidney disease (ESKD), lowering symptom burden is likely more important than solely the prolongation of life. ESKD-related symptoms are multifactorial and dialysis initiation may affect distinct symptoms differently [1]. Symptoms caused by fluid overload (e.g. leg swelling) may be expected to improve, whereas those related to uremic toxins (e.g. itch) may remain. This, since protein-bound uremic toxins are dependent on tubular secretion and thus not sufficiently removed by dialysis treatment [2]. Furthermore, dialysis treatment itself may cause additional symptoms (e.g. fatigue). Therefore, we investigated the evolution of symptom burden and individual symptoms before and after starting dialysis in older ESKD patients. METHOD The European Quality (EQUAL) study is an ongoing prospective multicenter study in late stage 4/5 chronic kidney disease patients aged ≥65 years. Between April 2012 and December 2021, 30 kidney disease-related symptoms were assessed every 3–6 months using the dialysis symptom index (DSI). The sum score for symptom number ranges from 0 to 30 and for symptom severity from 0 to 150, with higher scores indicating a higher burden. We used mixed-effects models to study symptom burden and individual symptoms during the year preceding and following dialysis initiation. RESULTS In total, 456 incident dialysis patients were included. At baseline, dialysis initiation, mean (SD) age was 77 (6) years, eGFR 8 (4) mL/min/1.73 m2 75% were men, 45% had diabetes, 9% smoked and 45% had a history of cardiovascular disease. Mean (SD) number of symptoms was 15 (7) with a symptom severity of 46 (24). During the year preceding dialysis, symptom number increased by +3.4 [95% confidence interval (95% CI): +2.4 to +4.4] and severity by +13.9 (95% CI: +10.1 to +17.6). In the year following dialysis, symptom number decreased by –1.0 (95% CI: −2.1 to + 0.0) and symptom severity by –6.9 (95% CI: −10.8 to −3.0) (Figure 1). At start of dialysis, fatigue, decreased interest in sex and difficulty becoming sexually aroused had the highest prevalence of 81%, 69% and 68%, respectively, and highest burden with a mean severity of 2.7, 2.4 and 2.3, respectively. We observed three separate patterns in prevalence and severity of individual symptoms: (1) increase in the year before dialysis initiation and decrease in the year after (fatigue, trouble staying asleep, leg swelling, decreased appetite, shortness of breath, worrying, trouble falling asleep, difficulty concentrating, feeling irritable, feeling sad, feeling nervous, nausea, feeling anxious, constipation, restless legs and chest pain); (2) increase in the year before dialysis initiation and no change or continued increase in the year after (decreased interest in sex, difficulty becoming sexually aroused, itch, bone or joint pain, dizziness, diarrhea, tingling in feet and vomiting); and (3) no change in the year before or after dialysis initiation (muscle cramps, dry skin, dry mouth, muscle soreness, cough and headache) (Figure 2). CONCLUSION Symptom burden worsened considerably before dialysis initiation, and halted afterwards. Fatigue was the most common and burdensome symptom. Our results may emphasize the importance of discussing kidney-disease related symptoms in routine clinical care and considering their differing patterns of evolution before and after dialysis initiation. Increased physician awareness may lead to better symptom control and has been shown to improve total symptom burden [3].

Objective: To investigate the impact of the coronavirus pandemic on mental health in hemodialysis patients, we assessed depression, anxiety and quality of life with valid mental health measures before and after the start of the pandemic. Methods: Data were used from 121 hemodialysis patients from the ongoing prospective multicenter DIVERS-II study. COVID-19 related stress was measured with the Perceived Stress Scale – 10, depression with the Beck Depression Inventory – second edition (BDI-II)), anxiety with the Beck Anxiety Inventory (BAI) and quality of life with the Short Form – 12 (SF-12). Scores during the first and second COVID-19 wave in the Netherlands were compared to data prior to the pandemic with linear mixed models. Results: No significant differences were found in BDI-II, BAI and SF-12 scores between before and during the pandemic. During the first wave, 33% of participants reported COVID-19 related stress and in the second wave 37%. These patients had higher stress levels (mean difference (MD) 4.7 (95%CI 1.5; 8.0), p = 0.005) and BDI-II scores (MD 4.9 (95%CI 0.7; 9.0), p = 0.021) and lower SF-12 mental component summary scores (MD -5.3 (95%CI -9.0, −1.6), p = 0.006) than patients who did not experienced COVID-19 stress. These differences were already present before the pandemic. Conclusion: The COVID-19 pandemic does not seem to influence mental health in hemodialysis patients. However, a substantial subgroup of patients with pre-existent mental health problems may be more susceptible to experience COVID-19 related stress.

ObjectivesThe medical field is facing a clinician-scientist shortage. Medical schools could foster the clinician-scientist workforce by offering students research opportunities. Most medical schools offer elective research programmes. Subsequently, a subset of doctors graduates without any research experience. Mandatory research projects may be more sufficient to develop clinician-scientist, but take more supervision and curricular time. There is limited insight in the scientific outcomes of mandatory research experiences. This study aims to examine publication rates of a mandatory research experience, identify factors associated with publication, and includes postgraduate research engagement.Design and settingProspective follow-up study involving 10 cohorts of medical students’ mandatory research projects from Leiden University Medical Center.ParticipantsAll medical students who conducted their research project between 2008 and 2018 (n=2329) were included.Main outcome measurePublication rates were defined as peer-reviewed scientific publications, including research papers, reviews, and published meeting abstracts. Postgraduate research engagement was defined as research participation and dissemination of research at scientific conferences or in journals.ResultsIn total, 644 (27.7%) of all mandatory research experiences resulted in publication, with students mainly as first (n=984, 42.5%) or second author (n=587, 25.3%) and above world average citation impact (mean normalised journal score 1.29, mean normalised citation score 1.23). Students who conducted their research in an academic centre (adjusted OR 2.82; 95% CI 2.10 to 3.77), extended their research (adjusted OR 1.73; 95% CI 1.35 to 2.20), were involved in an excellency track (adjusted OR 2.08; 95% CI 1.44 to 3.01), or conducted clinical (adjusted OR 2.08; 95% CI 1.15 to 3.74) or laboratory (adjusted OR 2.16; 95% CI 1.16 to 4.01) research published their research more often. Later as junior doctors, this group significantly more often disseminate their research results at scientific conferences (adjusted OR 1.89; 95% CI 1.11 to 3.23) or in journals (adjusted OR 1.98; 95% CI 1.14 to 3.43).ConclusionsOur findings suggest that a significant subset of hands-on mandatory research projects with flexible learning pathways result in tangible research output with proper impact and that such successful experiences can be considered as diving board towards a research-oriented career.

Objective: To investigate the effectiveness of a guided internet-based self-help intervention for hemodialysis patients with depressive symptoms. Method: Chronic hemodialysis patients from nine Dutch hospitals with a depression score on the Beck Depression Inventory – second edition (BDI-II) of ≥10, were cluster-randomized into a five modules guided internet-based self-help problem solving therapy intervention or a parallel care-as-usual control group. Clusters were based on hemodialysis shift. The primary outcome depression was measured with the BDI-II. Analysis was performed with linear mixed models. Results: A total of 190 hemodialysis patients were cluster-randomized to the intervention (n = 89) or control group (n = 101). Post-intervention measurement was completed by 127 patients (67%) and more than half of the patients (54%) completed the intervention. No significant differences were found on the BDI-II score between the groups (mean difference − 0.1, 95%CI -3.0; 2.7, p = 0.94). Per protocol sensitivity analysis showed comparable results. No significant differences in secondary outcomes were observed between groups. Conclusions: Guided internet-based self-help problem solving therapy for hemodialysis patients with depressive symptoms does not seem to be effective in reducing these symptoms as compared to usual care. Future research should examine how to best design content and accessibility of an intervention for depressive symptoms in hemodialysis patients. Trial registration: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

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.

690 Background: Recent pancreatic cancer surveillance programs of high-risk individuals have reported improved outcomes. This study assessed to what extent outcomes of pancreatic ductal adenocarcinoma (PDAC) in patients with a CDKN2A/p16 pathogenic variant (PV) diagnosed during surveillance are better as compared to PDAC patients diagnosed outside surveillance. Methods: In a propensity score matched cohort using data from the Netherlands Cancer Registry, we compared resectability, stage and survival between patients diagnosed in surveillance with non-surveillance PDAC patients. Survival analysis were repeated after adjustment for lead-time bias. Results: Between January 2000 and December 2020, 43 762 patients with PDAC were identified from the NCR. Thirty-one patients with PDAC in surveillance were matched in a 1:5 ratio with 155 non-surveillance patients based on age at diagnosis, sex, and year of diagnosis. In total, 71% of patients in surveillance, as compared to 16% of non-surveillance patients underwent a surgical resection (OR 14.03; 95% CI, 5.92 – 35.85). In surveillance, 39% of patients was diagnosed with stage I cancer, as compared to 6% of non-surveillance PDAC patients (OR 0.10; 95% CI, 0.04 – 0.21). Patients in surveillance had a better prognosis, reflected by a 3-year survival of 32.4% and a median overall survival (OS) of 26.8 months vs. 1.4% 3-year survival and 5.3 months median OS in non-surveillance patients (HR 0.22; 95% 0.14 – 0.36). After adjustment for lead time, PDAC diagnosis in surveillance remained strongly associated with improved survival. Conclusions: Surveillance for PDAC in carriers of a CDKN2A/p16 PV results in earlier detection, increased resectability and improved survival as compared to non-surveillance PDAC patients.[Table: see text]