Adherence and persistence to novel glucose-lowering medications in persons with type 2 diabetes mellitus undergoing routine care.

AIMS: To assess adherence and persistence to sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and dipeptidyl peptidase-4 inhibitors (DPP4i) in routine care. METHODS: Using retrospective healthcare data from the Stockholm region, Sweden, we evaluated new-users of these agents during 2015-2020. We investigated adherence (≥80 % of days covered by an active supply), persistence (no treatment gap ≥ 60 days), and predictors for non-adherence and non-persistence. RESULTS: We identified 24,470 new-users of SGLT2i (10,743), GLP1-RA (10,315), and/or DPP4i (9,488). Over 2.8 years median follow-up, the proportion demonstrating adherence was higher for SGLT2i (57 %) than DPP4i (53 %, comparison p < 0.001), and for GLP1-RA than DPP4i (54 % vs 53 %, p < 0.001). Similarly, persistence was higher for both SGLT2i and GLP-RA than DPP4i (respectively, 50 % vs 44 %, p < 0.001; 49 % vs 44 %, p < 0.001). Overall adherence was better among users who were older, had a history of high blood pressure, used more non-diabetic medications, had lower Hba1c, had better kidney function, and had completed secondary schooling or university. Women had worse adherence to SGLT2i and GLP1-RA than DPP4i. CONCLUSIONS: We report adherence and persistence to SGLT2i, GLP1-RA and DPP4i in routine care, and identify prognostic factors that could inform implementation interventions to improve uptake of these important therapies.

Understanding students' feedback use in medical progress testing: A qualitative interview study.

BACKGROUND: Active engagement with feedback is crucial for feedback to be effective and improve students' learning and achievement. Medical students are provided feedback on their development in the progress test (PT), which has been implemented in various medical curricula, although its format, integration and feedback differ across institutions. Existing research on engagement with feedback in the context of PT is not sufficient to make a definitive judgement on what works and which barriers exist. Therefore, we conducted an interview study to explore students' feedback use in medical progress testing. METHODS: All Dutch medical students participate in a national, curriculum-independent PT four times a year. This mandatory test, composed of multiple-choice questions, provides students with written feedback on their scores. Furthermore, an answer key is available to review their answers. Semi-structured interviews were conducted with 21 preclinical and clinical medical students who participated in the PT. Template analysis was performed on the qualitative data using a priori themes based on previous research on feedback use. RESULTS: Template analysis revealed that students faced challenges in crucial internal psychological processes that impact feedback use, including 'awareness', 'cognizance', 'agency' and 'volition'. Factors such as stakes, available time, feedback timing and feedback presentation contributed to these difficulties, ultimately hindering feedback use. Notably, feedback engagement was higher during clinical rotations, and students were interested in the feedback when seeking insights into their performance level and career perspectives. CONCLUSION: Our study enhanced the understanding of students' feedback utilisation in medical progress testing by identifying key processes and factors that impact feedback use. By recognising and addressing barriers in feedback use, we can improve both student and teacher feedback literacy, thereby transforming the PT into a more valuable learning tool.

An increase in albuminuria is associated with a higher incidence of malignancies.

Background: A single albuminuria measurement is reported to be an independent predictor of cancer risk. Whether change in albuminuria is also independently associated with cancer is not known. Methods: We included 64 303 subjects of the Stockholm CREAtinine Measurements (SCREAM) project without a history of cancer and with at least two urine albumin-creatinine ratio (ACR) tests up to 2 years apart. Albuminuria changes were quantified by the fold-change in ACR over 2 years, and stratified into the absence of clinically elevated albuminuria (i.e. never), albuminuria that remained constant, and albuminuria that increased or decreased. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidences. Results: During a median follow-up of 3.7 (interquartile range 3.6-3.7) years, 5126 subjects developed de novo cancer. After multivariable adjustment including baseline estimated glomerular filtration rate and baseline ACR, subjects with increasing ACR over 2 years had a 19% (hazard ratio 1.19; 95% confidence interval 1.08-1.31) higher risk of overall cancer compared with those who never had clinically elevated ACR. No association with cancer risk was seen in the groups with decreasing or constant ACR. Regarding site-specific cancer risks, subjects with increasing ACR or constant ACR had a higher risk of developing urinary tract and lung cancer. No other associations between 2-year ACR changes and site-specific cancers were found. Conclusions: Increases in albuminuria over a 2-year period are associated with a higher risk of developing overall, urinary tract and lung cancer, independent of baseline kidney function and albuminuria. These data add important weight to the link that exists between albuminuria and cancer incidence.

Does 'summative' count? The influence of the awarding of study credits on feedback use and test-taking motivation in medical progress testing.

Despite the increasing implementation of formative assessment in medical education, its' effect on learning behaviour remains questionable. This effect may depend on how students value formative, and summative assessments differently. Informed by Expectancy Value Theory, we compared test preparation, feedback use, and test-taking motivation of medical students who either took a purely formative progress test (formative PT-group) or a progress test that yielded study credits (summative PT-group). In a mixed-methods study design, we triangulated quantitative questionnaire data (n = 264), logging data of an online PT feedback system (n = 618), and qualitative interview data (n = 21) to compare feedback use, and test-taking motivation between the formative PT-group (n = 316), and the summative PT-group (n = 302). Self-reported, and actual feedback consultation was higher in the summative PT-group. Test preparation, and active feedback use were relatively low and similar in both groups. Both quantitative, and qualitative results showed that the motivation to prepare and consult feedback relates to how students value the assessment. In the interview data, a link could be made with goal orientation theory, as performance-oriented students perceived the formative PT as not important due to the lack of study credits. This led to low test-taking effort, and feedback consultation after the formative PT. In contrast, learning-oriented students valued the formative PT, and used it for self-study or self-assessment to gain feedback. Our results indicate that most students are less motivated to put effort in the test, and use feedback when there are no direct consequences. A supportive assessment environment that emphasizes recognition of the value of formative testing is required to motivate students to use feedback for learning.

[Learning from assessment: how quality questions can stimulate learning]. / Leren van toetsen.

Assessment plays a significant role in the career of medical doctors. Not only are they being assessed, many medical doctors are also involved in teaching which includes the creation of tests. Therefore, knowledge on high quality assessment questions is essential. Multiple-choice questions (MCQs) are commonly used, but allow for cueing, stimulates recognition-based learning and do not align clinical practice. The Very Short Answer Question (VSAQ), an open-ended question with a limited answer, is a good alternative which does not allow for cueing, is authentic and encourages students to study more actively. The marking time of VSAQs is relatively short and plausible alternative answer options are no longer needed. It's time to challenge the limits of our comfort zone and to dare using VSAQs in our assessments more often. This way, good and representative assessments can stimulate the learning process of medical doctors and form a strong fundament for professional practice.

A tool to predict the risk of lower extremity amputation in patients starting dialysis.

BACKGROUND AND HYPOTHESIS: Non-traumatic lower extremity amputation (LEA) is a severe complication during dialysis. To inform decision-making for physicians, we developed a multivariable prediction model for LEA after starting dialysis. METHODS: Data from the Swedish Renal Registry (SNR) between 2010 and 2020 were geographically split into a development and validation cohort. Data from NECOSAD between 1997 and 2009 were used for validation targeted at Dutch patients. Inclusion criteria were no previous LEA and kidney transplant and age ≥ 40 years at baseline. A Fine-Gray model was developed with LEA within 3 years after starting dialysis as outcome of interest. Death and kidney transplant were treated as competing events. One coefficient, ordered by expected relevance, per 20 events was estimated. Performance was assessed with calibration and discrimination. RESULTS: SNR was split into an urban development cohort with 4 771 individuals experiencing 201 (4.8%) events and a rural validation cohort with 4.876 individuals experiencing 155 (3.2%) events. NECOSAD contained 1 658 individuals experiencing 61 (3.7%) events. Ten predictors were included: female sex, age, diabetes mellitus, peripheral artery disease, cardiovascular disease, congestive heart failure, obesity, albumin, haemoglobin and diabetic retinopathy. In SNR, calibration intercept and slope were -0.003 and 0.912 respectively. The C-index was estimated as 0.813 (0.783-0.843). In NECOSAD, calibration intercept and slope were 0.001 and 1.142 respectively. The C-index was estimated as 0.760 (0.697-0.824). Calibration plots showed good calibration. CONCLUSION: A newly developed model to predict LEA after starting dialysis showed good discriminatory performance and calibration. By identifying high-risk individuals this model could help select patients for preventive measures.

Prognostic Models in Nephrology: Where Do We Stand and Where Do We Go from Here? Mapping Out the Evidence in a Scoping Review.

Prognostic models can strongly support individualized care provision and well-informed shared decision making. There has been an upsurge of prognostic research in the field of nephrology, but the uptake of prognostic models in clinical practice remains limited. Therefore, we map out the research field of prognostic models for kidney patients and provide directions on how to proceed from here. We performed a scoping review of studies developing, validating, or updating a prognostic model for patients with CKD. We searched all published models in PubMed and Embase and report predicted outcomes, methodological quality, and validation and/or updating efforts. We found 602 studies, of which 30.1% concerned CKD populations, 31.6% dialysis populations, and 38.4% kidney transplantation populations. The most frequently predicted outcomes were mortality ( n =129), kidney disease progression ( n =75), and kidney graft survival ( n =54). Most studies provided discrimination measures (80.4%), but much less showed calibration results (43.4%). Of the 415 development studies, 28.0% did not perform any validation and 57.6% performed only internal validation. Moreover, only 111 models (26.7%) were externally validated either in the development study itself or in an independent external validation study. Finally, in 45.8% of development studies no useable version of the model was reported. To conclude, many prognostic models have been developed for patients with CKD, mainly for outcomes related to kidney disease progression and patient/graft survival. To bridge the gap between prediction research and kidney patient care, patient-reported outcomes, methodological rigor, complete reporting of prognostic models, external validation, updating, and impact assessment urgently need more attention.

Albuminuria and the risk of cancer: the Stockholm CREAtinine Measurements (SCREAM) project.

Background: Studies investigating the association of chronic kidney disease and cancer have focused on estimated glomerular filtration (eGFR) rather than on albuminuria. This study aimed to examine whether albuminuria is associated with cancer incidence, and whether this association is independent of eGFR. Methods: We included subjects of the Stockholm Creatinine Measurements (SCREAM) project without a history of cancer-250 768 subjects with at least one urine albumin-creatinine ratio (ACR) test (primary cohort) and 433 850 subjects with at least one dipstick albuminuria test (secondary cohort). Albuminuria was quantified as KDIGO albuminuria stages. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidence rates. Multivariable Cox proportional hazards regression models adjusted for confounders including eGFR to calculate hazard ratios and 95% confidence intervals (HRs, 95% CIs). Results: During a median follow-up of 4.3 (interquartile range 2.0-8.2) years, 21 901 subjects of the ACR cohort developed de novo cancer. In multivariable analyses, adjusting among others for eGFR, subjects with an ACR of 30-299 mg/g or ≥300 mg/g had a 23% (HR 1.23; 95% CI 1.19-1.28) and 40% (HR 1.40; 95% CI 1.31-1.50) higher risk of developing cancer, respectively, when compared with subjects with an ACR <30 mg/g. This graded, independent association was also observed for urinary tract, gastrointestinal tract, lung and hematological cancer incidence (all P < .05). Results were similar in the dipstick albuminuria cohort. Conclusions: Albuminuria was associated with the risk of cancer independent of eGFR. This association was primarily driven by a higher risk of urinary tract, gastrointestinal tract, lung and hematological cancers.

Use of very short answer questions compared to multiple choice questions in undergraduate medical students: An external validation study.

Multiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs), which are open-ended questions requiring a very short answer, may circumvent these limitations. Although VSAQ use in medical assessment increases, almost all research on reliability and validity of VSAQs in medical education has been performed by a single research group with extensive experience in the development of VSAQs. Therefore, we aimed to validate previous findings about VSAQ reliability, discrimination, and acceptability in undergraduate medical students and teachers with limited experience in VSAQs development. To validate the results presented in previous studies, we partially replicated a previous study and extended results on student experiences. Dutch undergraduate medical students (n = 375) were randomized to VSAQs first and MCQs second or vice versa in a formative exam in two courses, to determine reliability, discrimination, and cueing. Acceptability for teachers (i.e., VSAQ review time) was determined in the summative exam. Reliability (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 (average 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. Positive cueing occurred more in MCQs than in VSAQs (20% vs. 4% and 20.8% vs. 8.3% of questions per person in both courses). This study validates the positive results regarding VSAQs reliability, discrimination, and acceptability in undergraduate medical students. Furthermore, we demonstrate that VSAQ use is reliable among teachers with limited experience in writing and marking VSAQs. The short learning curve for teachers, favourable marking time and applicability regardless of the topic suggest that VSAQs might also be valuable beyond medical assessment.

Systematic metareview of prediction studies demonstrates stable trends in bias and low PROBAST inter-rater agreement.

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.

Prevalence of chronic kidney disease in women of reproductive age and observed birth rates.

INTRODUCTION: Women of reproductive age with chronic kidney disease (CKD) are recognised to have decreased fertility and a higher risk of adverse pregnancy outcomes. How often CKD afflicts women of reproductive age is not well known. This study aimed to evaluate the burden of CKD and associated birth rates in an entire region. METHODS: This was a retrospective cohort study including women of childbearing age in Stockholm during 2006-2015. We estimated the prevalence of "probable CKD" by the presence of an ICD-10 diagnosis of CKD, a single estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or history of maintenance dialysis. By linkage with the Swedish Medical Birth Register we identified births during the subsequent three years from study inclusion and evaluated birth rates. RESULTS: We identified 817,730 women in our region, of whom 55% had at least one creatinine measurement. A total of 3938 women were identified as having probable CKD, providing an age-averaged CKD prevalence of 0.50%. Women with probable CKD showed a lower birth rate 3 years after the index date (35.7 children per 1000 person years) than the remaining women free from CKD (46.5 children per 1000 person years). CONCLUSION: As many as 0.50% of individuals in this cohort had probable CKD, defined on the basis of at least one eGFR<60 ml/min1.73 m2 test result, dialysis treatment (i.e. CKD stages 3-5) or an ICD-10 diagnosis of CKD. This prevalence is lower than previous estimates. Women with probable CKD, according to a study mainly capturing CKD 3-5, had a lower birth rate than those without CKD, illustrating the challenges of this population to successfully conceive.

Use of guideline-recommended medical therapy in patients with heart failure and chronic kidney disease: from physician's prescriptions to patient's dispensations, medication adherence and persistence.

AIM: Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence-based medical therapies in HF across CKD stages. METHODS AND RESULTS: We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure Registry in 2009-2018. We investigated the likelihood of physicians to prescribe guideline-recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered ≥80%) and persist (continued use) on these treatments during the first year of therapy. We identified 31 668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNi) were 96%, 92%, 86%, and 68%, for estimated glomerular filtration rate (eGFR) ≥60, 45-59, 30-44, and <30 ml/min/1.73 m2 , respectively; for beta-blockers 94%, 93%, 92%, and 92%, for mineralocorticoid receptor antagonists (MRAs) 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi + beta-blockers + MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n = 15 114). CONCLUSIONS: Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence-based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials.

Stopping versus continuing renin-angiotensin-system inhibitors after acute kidney injury and adverse clinical outcomes: an observational study from routine care data.

Background: 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. Methods: We analysed outcomes of long-term RASi users experiencing AKI (stage 2 or 3, or clinically coded) during hospitalization in Stockholm and Sweden during 2007-18. We compared stopping RASi within 3 months after discharge with continuing RASi. The primary study outcome was the composite of all-cause mortality, myocardial infarction (MI) 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 (HRs), balancing 75 confounders. Weighted absolute risk differences (ARDs) 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. The 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 (CI)] of the composite of death, MI 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). Discussion: 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, MI and stroke.

Comparative effectiveness of SGLT2i versus GLP1-RA on cardiovascular outcomes in routine clinical practice.

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 difference 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.

Conducting correlation analysis: important limitations and pitfalls.

The correlation coefficient is a statistical measure often used in studies to show an association between variables or to look at the agreement between two methods. In this paper, we will discuss not only the basics of the correlation coefficient, such as its assumptions and how it is interpreted, but also important limitations when using the correlation coefficient, such as its assumption of a linear association and its sensitivity to the range of observations. We will also discuss why the coefficient is invalid when used to assess agreement of two methods aiming to measure a certain value, and discuss better alternatives, such as the intraclass coefficient and Bland-Altman's limits of agreement. The concepts discussed in this paper are supported with examples from literature in the field of nephrology.

Acute kidney injury and kidney replacement therapy in COVID-19: a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) can affect hospitalized patients with coronavirus disease 2019 (COVID-19), with estimates ranging between 0.5% and 40%. We performed a systematic review and meta-analysis of studies reporting incidence, mortality and risk factors for AKI in hospitalized COVID-19 patients. METHODS: We systematically searched 11 electronic databases until 29 May 2020 for studies in English reporting original data on AKI and kidney replacement therapy (KRT) in hospitalized COVID-19 patients. Incidences of AKI and KRT and risk ratios for mortality associated with AKI were pooled using generalized linear mixed and random-effects models. Potential risk factors for AKI were assessed using meta-regression. Incidences were stratified by geographic location and disease severity. RESULTS: A total of 3042 articles were identified, of which 142 studies were included, with 49 048 hospitalized COVID-19 patients including 5152 AKI events. The risk of bias of included studies was generally low. The pooled incidence of AKI was 28.6% [95% confidence interval (CI) 19.8-39.5] among hospitalized COVID-19 patients from the USA and Europe (20 studies) and 5.5% (95% CI 4.1-7.4) among patients from China (62 studies), whereas the pooled incidence of KRT was 7.7% (95% CI 5.1-11.4; 18 studies) and 2.2% (95% CI 1.5-3.3; 52 studies), respectively. Among patients admitted to the intensive care unit, the incidence of KRT was 20.6% (95% CI 15.7-26.7; 38 studies). Meta-regression analyses showed that age, male sex, cardiovascular disease, diabetes mellitus, hypertension and chronic kidney disease were associated with the occurrence of AKI; in itself, AKI was associated with an increased risk of mortality, with a pooled risk ratio of 4.6 (95% CI 3.3-6.5). CONCLUSIONS: AKI and KRT are common events in hospitalized COVID-19 patients, with estimates varying across geographic locations. Additional studies are needed to better understand the underlying mechanisms and optimal treatment of AKI in these patients.