Epidemiological studies often aim to investigate the causal contribution of a risk factor to a disease or other outcome. In etiological research, one is usually interested in the (biological)... Show moreEpidemiological studies often aim to investigate the causal contribution of a risk factor to a disease or other outcome. In etiological research, one is usually interested in the (biological) mechanism(s) underlying the studied relationship. Inappropriate conduct of an etiological study may have major implications for the correctness of the results and interpretation of the findings. Therefore, in this paper, we aim to describe step by step how etiological research should be carried out, together with its common pitfalls. These steps involve finding and formulating a well-defined etiological research question, choosing an appropriate study design including a suitable comparison group, adequate modelling, and adequate reporting and interpretation of the results. Show less
Background Cohort studies are among the most robust of observational studies but have issues with external validity. This study assesses threats to external validity (generalizability) in the... Show moreBackground Cohort studies are among the most robust of observational studies but have issues with external validity. This study assesses threats to external validity (generalizability) in the European QUALity (EQUAL) study, a cohort study of people >65 years of age with Stage 4/5 chronic kidney disease. Methods Patients meeting the EQUAL inclusion criteria were identified in The Health Improvement Network database and stratified into those attending renal units, a secondary care cohort (SCC) and a not primary care cohort (PCC). Survival, progression to renal replacement therapy (RRT) and hospitalization were compared. Results The analysis included 250, 633 and 2464 patients in EQUAL, PCC and SCC. EQUAL had a higher proportion of men compared with PCC and SCC (60.0% versus 34.8% versus 51.4%). Increasing age >= 85 years {odds ratio [OR] 0.25 [95% confidence interval (CI) 0.15-0.40]} and comorbidity [Charlson Comorbidity Index >= 4, OR 0.69 (95% CI 0.52-0.91)] were associated with non-participation in EQUAL. EQUAL had a higher proportion of patients starting RRT at 1 year compared with SCC (8.1% versus 2.1%; P < 0.001). Patients in the PCC and SCC had increased risk of hospitalization [incidence rate ratio 1.76 (95% CI 1.27-2.47) and 2.13 (95% CI 1.59-2.86)] and mortality at 1 year [hazard ratio 3.48 (95% CI 2.1-5.7) and 1.7 (95% CI 1.1-2.7)] compared with EQUAL. Conclusions This study provides evidence of how participants in a cohort study can differ from the broader population of patients, which is essential when considering external validity and application to local practice. Show less
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... Show moreBackground. 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 < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021].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. Show less
In nephrology, a great deal of information is measured repeatedly in patients over time, often alongside data on events of clinical interest. In this introductory article we discuss how these two... Show moreIn nephrology, a great deal of information is measured repeatedly in patients over time, often alongside data on events of clinical interest. In this introductory article we discuss how these two types of data can be simultaneously analysed using the joint model (JM) framework, illustrated by clinical examples from nephrology. As classical survival analysis and linear mixed models form the two main components of the JM framework, we will also briefly revisit these techniques. Show less
Study quality depends on a number of factors, one of them being internal validity. Such validity can be affected by random and systematic error, the latter also known as bias. Both make it more... Show moreStudy quality depends on a number of factors, one of them being internal validity. Such validity can be affected by random and systematic error, the latter also known as bias. Both make it more difficult to assess a correct frequency or the true relationship between exposure and outcome. Where random error can be addressed by increasing the sample size, a systematic error in the design, the conduct or the reporting of a study is more problematic. In this article, we will focus on bias, discuss different types of selection bias (sampling bias, confounding by indication, incidence-prevalence bias, attrition bias, collider stratification bias and publication bias) and information bias (recall bias, interviewer bias, observer bias and lead-time bias), indicate the type of studies where they most frequently occur and provide suggestions for their prevention. Show less
Background-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic... Show moreBackground-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis.Methods and Results-The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged >= 65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m(2)). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (<= 14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19; P<0.0001). Each 15 mL/min/1.73 m(2) lower mean estimated GFR was associated with a 23% (95% CI, 14-31; P<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%; P<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%).Conclusions-In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m2 lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors. Show less
Voskamp, P.W.M.; Diepen, M. van; Evans, M.; Caskey, F.J.; Torino, C.; Postorino, M.; ... ; EQUAL Study Investigators 2019
Background. Quality of life (QoL) is an important outcome in chronic kidney disease (CKD). Patients feel that symptoms are an important determinant of QoL. However, this relation is unknown. The... Show moreBackground. Quality of life (QoL) is an important outcome in chronic kidney disease (CKD). Patients feel that symptoms are an important determinant of QoL. However, this relation is unknown. The aims of this study were to investigate the impact of the number and severity of symptoms on QoL in elderly pre-dialysis patients, assessed by both the effect of symptoms and their importance relative to kidney function, and other clinical variables on QoL.Methods. The European Quality study (EQUAL study) is an ongoing European prospective follow-up study in late Stage 4/5 CKD patients aged >= 65 years. We used patients included between March 2012 and December 2015. Patients scored their symptoms with the Dialysis Symptom Index, and QoL with the research and development-36 (RAND-36) item Health Survey (RAND-36). The RAND-36 results in a physical component summary (PCS) and a mental component summary (MCS). We used linear regression to estimate the relation between symptoms and QoL at baseline and after 6 months, and to calculate the variance in QoL explained by symptoms.Results. The baseline questionnaire was filled in by 1079 (73%) patients (median age 75 years, 66% male, 98% Caucasian), and the follow up questionnaire by 627 (42%) patients. At baseline, every additional symptom changed MCS with -0.81 [95% confidence interval (CI): -0.91 to -0.71] and PCS with -0.50 (95% CI: -0.62 to -0.39). In univariable analyses, number of symptoms explained 22% of MCS variance and 11% of PCS variance, whereas estimated glomerular filtration rate only explained 1%.Conclusions. In elderly CKD Stage 4/5 patients, symptoms have a substantial impact on QoL. This indicates symptoms should have a more prominent role in clinical decision-making. Show less
Luijtgaarden, M.W.M. van de; Caskey, F.J.; Wanner, C.; Chesnaye, N.C.; Postorino, M.; Janmaat, C.J.; ... ; EQUAL Study Investigators 2019
Background The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of >= 65years of age with... Show moreBackground The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of >= 65years of age with advanced CKD receiving routine nephrology care.Methods The European QUALity study on treatment in advanced chronic kidney disease (EQUAL) study follows patients from six European countries of >= 65years of age years whose estimated glomerular filtration rate (eGFR) dropped to <= 20mL/min/1.73m(2) for the first time during the last 6 months. The Dialysis Symptom Index was used to assess the prevalence and severity of 33 uraemic symptoms. Data on the clinical state at baseline were collected from medical records. Prevalence was standardized using the age distribution of women as the reference.Results The results in women (n=512) and men (n=967) did not differ with age (77.0 versus 75.7years) or eGFR (19.0 versus 18.5). The median number of symptoms was 14 [interquartile range (IQR) 9-19] in women, and 11 (IQR 7-16) in men. Women most frequently reported fatigue {39% [95% confidence interval (CI) 34-45]} and bone/joint pain [37% (95% CI 32-42)] as severe symptoms, whereas more men reported difficulty in becoming sexually aroused [32% (95% CI 28-35)] and a decreased interest in sex [31% (95% CI 28-35)]. Anaemia [73% (95% CI 69-77) versus 85% (95% CI 82-87)] was less common in women than in men, as were smoking history and cardiovascular comorbidity. However, a diagnosis of liver disease other than cirrhosis, psychiatric disease and mild malnutrition were more common among women.Conclusions Women in secondary care with an incident eGFR <= 20mL/min/1.73m(2) reported a higher symptom burden, while their clinical state was considered similar or even more favourable as compared with men. Show less
Windahl, K.; Irving, G.F.; Almquist, T.; Liden, M.K.; Luijtgaarden, M. van de; Chesnaye, N.C.; ... ; Evans, M. 2018
