ObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient... Show moreObjectivesDelirium is a serious condition, which poses treatment challenges during hospitalisation for COVID-19. Improvements in testing, vaccination and treatment might have changed patient characteristics and outcomes through the pandemic. We evaluated whether the prevalence and risk factors for delirium, and the association of delirium with in-hospital mortality changed through the pandemic.MethodsThis study was part of the COVID-OLD study in 19 Dutch hospitals including patients ≥70 years in the first (spring 2020), second (autumn 2020) and third wave (autumn 2021). Multivariable logistic regression models were used to study risk factors for delirium, and in-hospital mortality. Differences in effect sizes between waves were studied by including interaction terms between wave and risk factor in logistic regression models.Results1540, 884 and 370 patients were included in the first, second and third wave, respectively. Prevalence of delirium in the third wave (12.7%) was significantly lower compared to the first (22.5%) and second wave (23.5%). In multivariable-adjusted analyses, pre-existing memory problems was a consistent risk factor for delirium across waves. Previous delirium was a risk factor for delirium in the first wave (OR 4.02), but not in the second (OR 1.61) and third wave (OR 2.59, p-value interaction-term 0.028). In multivariable-adjusted analyses, delirium was not associated with in-hospital mortality in all waves.ConclusionDelirium prevalence declined in the third wave, which might be the result of vaccination and improved treatment strategies. Risk factors for delirium remained consistent across waves, although some attenuation was seen in the second wave. Show less
Background as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. Objective to investigate differences in characteristics, disease presentation and... Show moreBackground as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. Objective to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. Methods this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged >= 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality. Results a total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28-51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty. Conclusions compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality. The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions. Show less
Objectives Previous studies showed that high calcium intake may be associated with the reduced colorectal cancer (CRC) risk, but results were inconclusive. In this study, we evaluated whether... Show moreObjectives Previous studies showed that high calcium intake may be associated with the reduced colorectal cancer (CRC) risk, but results were inconclusive. In this study, we evaluated whether calcium intake from diet and supplements, as well as the calcium levels itself, were associated with the CRC risk in middle-aged and older individuals. Also, we evaluated whether these associations were modified by genetic variation of calcium homeostasis. Design This study was embedded in the Rotterdam study, a prospective cohort study among adults aged 55 years and older without CRC at baseline, from the Ommoord district of Rotterdam, The Netherlands (N = 10 941). Effect modification by a predefined polygenetic risk score (PRS) from seven loci known to be associated with calcium concentrations, was evaluated. Results The incidence rate of CRC in the study population was 2.9 per 1000 person-years. Relative to the recommended dietary calcium intake, only higher than the recommended dietary calcium intake (>= 1485 mg/day) was associated with a reduced risk of CRC [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.44-1.00]. No significant associations were found for calcium supplementation and only in the subgroup analysis, albumin-adjusted calcium levels were associated with an increased risk of CRC (HR = 1.11; 95% CI, 1.00-1.23). PRS showed effect modification in the association between calcium intake and CRC (P for interaction = 0.08). After stratification of PRS into low, intermediate and high, we found a lower CRC risk for low-weighted PRS per increase in calcium intake. Conclusion There is no consistent association between calcium indices on CRC. However, the association between calcium intake and CRC may be modified by genetic variation associated with serum calcium concentrations that deserves further replication in other studies with different population. Show less
BackgroundDuring the first wave of the COVID-19 pandemic older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been... Show moreBackgroundDuring the first wave of the COVID-19 pandemic older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting.ObjectiveThe aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands.MethodsThis was a multi-centre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality.ResultsA total of 1,376 patients were included (median age 78 years (IQR 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 vs. 7 days), lower oxygen demand and lower levels of CRP. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared to patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95%CI 1.3-3.0) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95%CI 1.8-4.3)).ConclusionsThe in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms. Show less
BackgroundThe association between obesity and lung cancer (LC) remains poorly understood. However, other indices of obesity on the basis of body shape instead of body size have not been examined... Show moreBackgroundThe association between obesity and lung cancer (LC) remains poorly understood. However, other indices of obesity on the basis of body shape instead of body size have not been examined yet. The aim of this study was to evaluate the association between different indices of body size and body shape and the risk of LC. In particular, this study examined the association between A Body Shape Index, a more precise indicator of abdominal fat than traditional anthropometric measures, and the risk of LC.MethodsIn the prospective cohort the Rotterdam Study, we analysed data of 9,689 participants. LC diagnoses were based on medical records and anthropometric measurements were assessed at baseline. Cox-regression analyses with corresponding Hazard Ratios were used to examine the association between the anthropometric measurements and the risk of LC with adjustment for potential confounders. Potential non-linear associations were explored with cubic splines using the Likelihood ratio (LR) test.ResultsDuring follow-up, 319 participants developed LC. Body mass Index (BMI) was inversely associated with the risk of lung cancer (HR 0.94, 95% CI: 0.91-0.97) and persisted after excluding lung cancer cases during the first 10 years of follow-up. There was evidence for a non-linear association between BMI and the risk of lung cancer (0,04, df = 1), which indicated that the inverse association between BMI and lung cancer was mainly present in non-obese participants. Waist circumference (WC) (HR 1.03 95% CI: 1.01-1.05), Waist-to-Hip Ratio (WHR) (HR 1.23 95% CI: 1.09-1.38) and ABSI (A Body Shape Index) (HR 1.17 95% CI: 1.05-1.30) were positively and linearly associated with the risk of lung cancer.ConclusionsBody shape rather than body size may be an important risk indicator of LC. Future research should focus on the role of visceral fat and the risk of LC as well as the underlying mechanisms. Show less
Lakeman, I.M.M.; Rodriguez-Girondo, M.; Lee, A.; Ruiter, R.; Stricker, B.H.; Wijnant, S.R.A.; ... ; Devilee, P. 2020
Purpose We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort,... Show morePurpose We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a polygenic risk score (PRS) based on 313 breast cancer (BC)-associated variants (PRS313) and other, nongenetic risk factors. Methods Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS(313)was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed to estimate the association between the PRS(313)and incident BC risk. Cumulative 10-year risks were calculated with BOADICEA including different sets of variables (age, risk factors and PRS313). C-statistics were used to evaluate discriminative ability. Results In total, 320 women developed BC. The PRS(313)was significantly associated with BC (hazard ratio [HR] per SD of 1.56, 95% confidence interval [CI] [1.40-1.73]). Using 10-year risk estimates including age and the PRS313, other risk factors improved the discriminatory ability of the BOADICEA model marginally, from a C-statistic of 0.636 to 0.653. Conclusions The effect size of the PRS(313)is highly reproducible in the Dutch population. Our results validate the BOADICEA v5 model for BC risk assessment in the Dutch general population. Show less
Fuentes, L. de las; Sung, Y.J.; Sitlani, C.M.; Avery, C.L.; Bartz, T.M.; Keyser, C. de; ... ; Whitsel, E.A. 2020
Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent... Show moreHypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 x 10(-8)) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy. Show less
Aims To evaluate the availability of pharmacokinetic, safety and efficacy analyses specifically targeted at elderly, prior to the authorization of drugs. Methods A cross-sectional, structured... Show moreAims To evaluate the availability of pharmacokinetic, safety and efficacy analyses specifically targeted at elderly, prior to the authorization of drugs. Methods A cross-sectional, structured review of publicly available initial approval documents of Food and Drug Administration-approved drugs was performed. The 10 most frequently on-label prescribed drug classes, drugs with known pharmacokinetic differences in the elderly or drugs that are relatively contraindicated in elderly (e.g. anticholinergics or benzodiazepines) were included in the analyses. Results In total, 1129 unique active pharmaceutical ingredients were found eligible for the analyses, of these, 506 were found in the Food and Drug Administration database (45%). The initial approval documents were available for 182 drugs. For the majority of the drugs, the initial approval documents in the database showed information on pharmacokinetics in elderly (n = 113; 62%). Furthermore, over time, the availability of information with regard to elderly increased statistically significantly from 0% in the period 1970-1979 to 76% for the period 2010-2018. Information on safety and efficacy was less frequently present, i.e. 42% and 45%, respectively and, moreover, the availability of information did not improve over time. Conclusion The under-representation of elderly in clinical trials thereby challenging the external validity of benefit/risk assessments of launched drugs was confirmed. Priority should be given to a study population that is representative for the target population. Show less
BackgroundA very high erythrocyte sedimentation rate (ESR) is usually an indication of underlying pathology. Additionally, a moderately elevated ESRmay also be attributable to biological ageing.... Show moreBackgroundA very high erythrocyte sedimentation rate (ESR) is usually an indication of underlying pathology. Additionally, a moderately elevated ESRmay also be attributable to biological ageing. Whether the ESR is a prognostic factor for mortality, regardless of age, has been scarcely investigated. Therefore, the objective was to analyse the association between elevated ESR levels and the risk of mortality in a prospective cohort of the general population.MethodsWe studied data from the Rotterdam Study (1990-2014). ESR levels were measured at baseline and individuals were followed until death or end of study. Associations between moderately (20-50mmh(-1)) and markedly (>50mmh(-1)) elevated ESR levels and all-cause mortality were assessed using multivariate Cox proportional hazard models.ResultsIn total, 5226 participants were included, and the mean age was 70.3years. During a median follow-up time of 14.9years, 3749 participants died (71.7%). After adjustment, both a moderately elevated ESR and a markedly elevated ESR were associated with a significantly higher risk of overall mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12-1.35 and HR 1.89, 95% CI 1.38-2.60, respectively]. Although the ESR becomes higher with age, in a group aged above 75years, without any comorbidities, an ESR>20mmh(-1) remained associated with a significantly increased risk of mortality (HR 1.29, 95%CI 1.01-1.64).ConclusionAn elevated ESR is an independent prognostic factor for mortality. Despite the fact that ESR increases with age, it remains associated with an increased risk of mortality and warrants close follow-up. Show less
