The work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related... Show moreThe work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related risk factors described in young and middle-aged populations and the risk of venous thrombosis (VT) in the elderly; second, we aimed to provide insight into several long-term consequences (i.e., health-related quality of life (HRQoL) and long-term risk of mortality) after a first VT at old age. Show less
Rosendal, C.; Arlien-Soborg, M.C.; Nielsen, E.H.; Andersen, M.S.; Feltoft, C.L.; Kistorp, C.; ... ; J. dal 2024
Acromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an... Show moreAcromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an epidemiological perspective and describe the temporal evolution of the disease pertaining to epidemiological variables, clinical presentation and mortality. We present updated epidemiological data from the population-based Danish cohort of patients with acromegaly (AcroDEN), along with meta-analyses of existing estimates from around the world.Based on this, we conclude that the incidence, prevalence and age at acromegaly diagnosis are all steadily increasing, but with considerable variation between studies. An increased number of incidental cases may contribute to the increase in incidence and age at diagnosis, respectively. The clinical features at presentation are trending toward a milder disease phenotype at diagnosis, and advances in therapeutic options have reduced the mortality of patients with acromegaly to a level similar to that of the general population. Moreover, the underlying cause of death has shifted from cardiovascular to malignant neoplastic diseases. Show less
BACKGROUND: Acute resection for left-sided obstructive colon carcinoma is thought to be associated with a higher mortality risk than a bridge-to-surgery approach using decompressing stoma or self... Show moreBACKGROUND: Acute resection for left-sided obstructive colon carcinoma is thought to be associated with a higher mortality risk than a bridge-to-surgery approach using decompressing stoma or self-expandable metal stent, but prediction models are lacking.OBJECTIVE: This study aimed to determine the influence of treatment strategy on mortality within 90 days from the first intervention in patients presenting with left-sided obstructive colon carcinoma.DESIGN: This was a national multicenter cohort study that used data from a prospective national audit.SETTINGS: The study was performed in 75 Dutch hospitals.PATIENTS: Patients were included if they underwent resection with curative intent for left-sided obstructive colon carcinoma between 2009 and 2016.INTERVENTIONS: First intervention was either acute resection, bridge to surgery with self-expandable metallic stent, or bridge to surgery with decompressing stoma.MAIN OUTCOME MEASURES: The main outcome measure was 90-day mortality after the first intervention. Risk factors were identified using multivariable logistic analysis. Subsequently, a risk model was developed.RESULTS: In total, 2395 patients were included, with the first intervention consisting of acute resection in 1848 patients (77%), stoma as bridge to surgery in 332 patients (14%), and stent as bridge to surgery in 215 patients (9%). Overall, 152 patients (6.3%) died within 90 days from the first intervention. A decompressing stoma was independently associated with lower 90-day mortality risk (HR, 0.27; 95% CI, 0.094–0.62). Other independent predictors for mortality were age, ASA classification, tumor location, and index levels of serum creatinine and C-reactive protein. The constructed risk model had an area under the curve of 0.84 (95% CI, 0.81–0.87).LIMITATIONS: Only patients who underwent surgical resection were included.CONCLUSIONS: Treatment strategy had a significant impact on 90-day mortality. A decompressing stoma considerably lowers the risk of mortality, especially in older and frail patients. The developed risk model needs further external validation. Show less
This thesis aims to improve patient outcomes after major oncological gastrointestinal surgery, by identifying targets for optimizing perioperative care. On the one hand, identifying (adjustable)... Show moreThis thesis aims to improve patient outcomes after major oncological gastrointestinal surgery, by identifying targets for optimizing perioperative care. On the one hand, identifying (adjustable) prognostic factors for postoperative complications and then using them in prediction models, and gaining insight into the quality of life after surgery. Improving preoperative risk assessment and subsequent personalization of postoperative care can reduce the rate of postoperative complications and mortality. In addition, risk prediction can support clinical knowledge in making treatment decisions. Modifiable prognostic factors are particularly important to identify as they may be optimized prior to surgery. Modifiable prognostic factors can then be used in prehabilitation programs to improve a patient's physical condition and thus improve patient outcomes. In addition, information about treatment consequences and treatment-related health problems is important for treatment decision-making for patients and healthcare professionals. Especially, if several treatment options are available, knowledge about (long-term) consequences of the treatment options is important for shared decision-making. This knowledge can also contribute to optimizing postoperative care and rehabilitation programs. In conclusion, the leads described in this thesis for improving postoperative care can be used to improve short- and long-term patient outcomes after complex oncological gastrointestinal surgery. Show less
PHARMACOM-EPI is a novel framework to predict plasma concentrations of drugs at the time of occurrence of clinical outcomes. In early 2021, the U.S. Food and Drug Administration (FDA) issued a... Show morePHARMACOM-EPI is a novel framework to predict plasma concentrations of drugs at the time of occurrence of clinical outcomes. In early 2021, the U.S. Food and Drug Administration (FDA) issued a warning on the anti-seizure drug lamotrigine claiming that it has the potential to increase the risk of arrhythmias and related sudden cardiac death due to a pharmacological sodium channel-blocking effect. We hypothesized that the risk of ar-rhythmias and related death is due to toxicity. We used the PHARMACOM-EPI framework to investigate the relationship between lamotrigine's plasma concentrations and the risk of death in older patients using real-world data. Danish nationwide administrative and healthcare registers were used as data sources and individuals aged 65 years or older during the period 1996 - 2018 were included in the study. According to the PHARMACOM-EPI framework, plasma concentrations of lamotrigine were predicted at the time of death and patients were cate-gorized into non-toxic and toxic groups based on the therapeutic range of lamotrigine (3-15 mg/L). Over 1 year of treatment, the incidence rate ratio (IRR) of all-cause mortality was calculated between the propensities score matched toxic and non-toxic groups. In total, 7286 individuals were diagnosed with epilepsy and were exposed to lamotrigine, 432 of which had at least one plasma concentration measurement The pharmacometric model by Chavez et al. was used to predict lamotrigine's plasma concentrations considering the lowest absolute percentage error among identified models (14.25 %, 95 % CI: 11.68-16.23). The majority of lamotrigine associated deaths were cardiovascular-related and occurred among individuals with plasma concentrations in the toxic range. The IRR of mortality between the toxic group and non-toxic group was 3.37 [95 % CI: 1.44-8.32] and the cumulative incidence of all-cause mortality exponentially increased in the toxic range. Application of our novel framework PHARMACOM-EPI provided strong evidence to support our hypothesis that the increased risk of all-cause and cardiovascular death was associated with a toxic plasma concentration level of lamotrigine among older lamo-trigine users. Show less
BackgroundMortality following hip fracture is high and incompletely understood. We hypothesize that hip musculature size and quality are related to mortality following hip fracture. This study aims... Show moreBackgroundMortality following hip fracture is high and incompletely understood. We hypothesize that hip musculature size and quality are related to mortality following hip fracture. This study aims to investigate the associations of hip muscle area and density from hip CT with death following hip fracture as well as assess the dependence of this association on time after hip fracture. MethodsIn this secondary analysis of the prospectively collected CT images and data from the Chinese Second Hip Fracture Evaluation, 459 patients were enrolled between May 2015 and June 2016 and followed up for a median of 4.5 years. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur. The Goutallier classification (GC) was used for qualitatively assessing muscle fat infiltration. Separate Cox models were used to predict mortality risk adjusted for covariates. ResultsAt the end of the follow-up, 85 patients were lost, 81 patients (64% women) had died, and 293 (71% women) survived. The mean age of non-surviving patients at death (82.0 +/- 8.1 years) was higher than that of the surviving patients (74.4 +/- 9.9 years). The Parker Mobility Score and the American Society of Anesthesiologists scores of the patients that died were respectively lower and higher compared to the surviving patients. Hip fracture patients received different surgical procedures, and no significant difference in the percentage of hip arthroplasty was observed between the dead and the surviving patients (P = 0.11). The cumulative survival was significantly lower for patients with low G.MaxM area and density and low G.Med/MinM density, independent of age and clinical risk scores. The GC grades were not associated with the mortality after hip fracture. Muscle density of both G.MaxM (adj. HR 1.83; 95% CI, 1.06-3.17) and G.Med/MinM (adj. HR 1.98; 95% CI, 1.14-3.46) was associated with mortality in the 1st year after hip fracture. G.MaxM area (adj. HR 2.11; 95% CI, 1.08-4.14) was associated with mortality in the 2nd and later years after hip fracture. ConclusionOur results for the first time show that hip muscle size and density are associated with mortality in older hip fracture patients, independent of age and clinical risk scores. This is an important finding to better understand the factors contributing to the high mortality in older hip fracture patients and to develop better future risk prediction scores that include muscle parameters. Show less
ObjectiveTextbook outcome (TO) is a composite outcome measure used in surgical oncology to compare hospital outcomes using multiple quality indicators. This study aimed to develop TO as an outcome... Show moreObjectiveTextbook outcome (TO) is a composite outcome measure used in surgical oncology to compare hospital outcomes using multiple quality indicators. This study aimed to develop TO as an outcome measure to assess healthcare quality for patients undergoing cytoreductive surgery (CRS) for advanced-stage ovarian cancer.MethodsThis population-based study included all CRS for FIGO IIIC-IVB primary ovarian cancer registered in the Netherlands between 2017 and 2020. The primary outcome was TO, defined as a complete CRS, combined with the absence of 30-day mortality, severe complications, and prolonged length of admission (≥ten days). Delayed start of adjuvant chemotherapy (≥six weeks) was not included in TO because of missing data. Logistic regressions were used to assess the association of case-mix factors with TO. Hospital variation was displayed using funnel plots.ResultsA total of 1909 CRS were included, of which 1434 were interval CRS and 475 were primary CRS. TO was achieved in 54% of the interval CRS cohort and 47% of the primary CRS cohort. Macroscopic residual disease after CRS was the most important factor for not achieving TO. Age ≥ 70 was associated with lower TO rates in multivariable logistic regressions. TO rates ranged from 40% to 69% between hospitals in the interval CRS cohort and 22% to 100% in the primary CRS cohort. In both analyses, one hospital had significantly lower TO rates (different hospitals). Case-mix adjustment significantly affected TO rates in the primary CRS analysis.ConclusionsTO is a suitable composite outcome measure to detect hospital variation in healthcare quality for patients with advanced-stage ovarian cancer undergoing CRS. Case-mix adjustment improves the accuracy of the hospital comparison. Show less
Dominguez-Valentin, M.; Haupt, S.; Seppälä, T.T.; Sampson, J.R.; Sunde, L.; Bernstein, I.; ... ; Moller, P. 2023
BackgroundThe Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including c...Show moreBackgroundThe Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time.MethodsThe PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender.FindingsGynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers.InterpretationIn path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Show less
This thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including... Show moreThis thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including laboratory, radiological, clinical and patient´s reported outcomes are presented.The Leiden NPSLE clinic is a tertiary referral center for patients with SLE and neuropsychiatric (NP) symptoms. In the NPSLE clinic, patients are assessed by a multidisciplinary team. Thereafter, clinical, radiological and laboratory measures are weighed in a consensus meeting to correctly attribute the NP symptoms: related to lupus activity (NPSLE) or not. This extensive and standardized assessment of NPSLE, a rare and heterogenous disease lacking a gold standard, is unique and creates the opportunity to explore many aspects of NPSLE in well-defined phenotypes.In the first part of this thesis, we evaluate both classification and treatment of patients withSLE and NP symptoms. The second part of this thesis focuses on a diverse range of clinicaloutcomes of NPSLE, including both morbidity and mortality. The last part of this thesisassesses potential biomarkers for (specific manifestations of) NPSLE. Show less
Slingerland-Boot, R.; Rooijakkers, E.; Koekkoek, K.; Blokland, D. van; Arbous, S.; Zanten, A. van 2023
BackgroundNormocaloric vs. calorie-restricted feeding in Intensive Care Unit (ICU) patients with refeeding hypophosphatemia (RH) is associated with increased mortality rates. Until now, only total... Show moreBackgroundNormocaloric vs. calorie-restricted feeding in Intensive Care Unit (ICU) patients with refeeding hypophosphatemia (RH) is associated with increased mortality rates. Until now, only total energy provision has been studied. Data on individual macronutrients (proteins, lipids, and carbohydrates) and clinical outcomes are lacking. This study evaluates associations between macronutrient intake among RH patients during the first week of ICU admission and clinical outcomes.MethodsA single-centre retrospective observational cohort study was conducted among prolonged mechanically ventilated RH ICU patients. The primary outcome was the association of separate macronutrient intakes during the first week of ICU admission with 6-month mortality, adjusted for relevant variables. Other parameters included ICU-, hospital- and 3-month mortality, mechanical ventilation duration and length of ICU and hospital stay. Macronutrient intakes were subsequently analyzed during day 1–3 and day 4–7 of ICU admission.ResultsIn total, 178 RH patients were included. Six-month all-cause mortality was 29.8%. Higher protein intake during days 1–3 of ICU admission (>0.71 g/kg∗day; HR 2.224, 95%CI 1.261–3.923, p = 0.006), higher age (HR 1.040, 95%CI 1.015–1.066, p = 0.002) and higher APACHE II scores on ICU admission (HR 1.086, 95%CI 1.034–1.140, p = 0.001) were associated with increased 6-month mortality. No differences in other outcomes were observed.ConclusionHigh protein - not carbohydrate or lipid - intake during the first three days of ICU admission in patients with RH is associated with increased 6-month mortality, but not short-term outcomes. We hypothesize a time-dependent and dose–response relationship between protein intake and mortality in refeeding hypophosphatemia ICU patients, although additional (randomized controlled) studies are needed to confirm this hypothesis. Show less
Purpose Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was... Show morePurpose Recent data have shown a decreasing overall mortality in acromegaly over the last decades. However, cancer incidence and cancer-related mortality still appear to be increased. Our aim was to obtain updated epidemiological data from Norway in a clinically well-defined cohort with complete register-based follow-up.Methods Patients diagnosed with acromegaly from South-Eastern Norway between 1999-2019 (n = 262) and age and sex matched population controls (1:100) were included (n = 26,200). Mortality and cancer data were obtained from the Norwegian Cause of Death and Cancer Registry. Mortality and cancer incidence were compared by Kaplan-Meier analyses and Cox regression; we report hazard ratios (HRs) with 95% confidence intervals (95% CI).Results Median age at diagnosis was 48.0 years (interquartile range (IQR): 37.6-58.0). Mean annual acromegaly incidence rate was 4.7 (95% CI 4.2-5.3) cases/10(6) person-years, and the point prevalence (2019) was 83 (95% CI 72.6-93.5) cases/10(6) persons. Overall mortality was not increased in acromegaly, HR 0.8 (95% CI 0.5-1.4), cancer-specific and cardiovascular-specific mortality was also not increased (HR: 0.7 (95% CI 0.3-1.8) and 0.8 (95% CI: 0.3-2.5) respectively). The HR for all cancers was 1.45 (1.0-2.1; p = 0.052).Conclusion In this large cohort study, covering the period 1999-2019, patients were treated with individualized multimodal management. Mortality was not increased compared to the general population and comparable with recent registry studies from the Nordic countries and Europe. Overall cancer risk was slightly, but not significantly increased in the patients. Show less
To compare hospitals' hip fracture patient mortality in a quality of care registry, correction for patient characteristics is needed. This study evaluates in 39,374 patients which characteristics... Show moreTo compare hospitals' hip fracture patient mortality in a quality of care registry, correction for patient characteristics is needed. This study evaluates in 39,374 patients which characteristics are associated with 30 and 90-day mortality, and showed how using these characteristics in a case mix-model changes hospital comparisons within the Netherlands. Purpose: Mortality rates after hip fracture surgery are considerable and may be influenced by patient characteristics. This study aims to evaluate hospital variation regarding patient demographics and disease burden, to develop a case-mix adjustment model to analyse differences in hip fracture patients' mortality to calculate case-mix adjusted hospital-specific mortality rates. Methods: Data were derived from 64 hospitals participating in the Dutch Hip Fracture Audit (DHFA). Adult hip fracture patients registered in 2017-2019 were included. Variation of case-mix factors between hospitals was analysed, and the association between case-mix factors and mortality at 30 and 90 days was determined through regression models. Results: There were 39,374 patients included. Significant variation in case-mix factors amongst hospitals was found for age >= 80 (range 25.8-72.1% p < 0.001), male gender (12.0-52.9% p < 0.001), nursing home residents (42.0-57.9% p < 0.001), pre-fracture mobility aid use (9.9-86.7% p < 0,001), daily living dependency (27.5-96.5% p < 0,001), ASA-class >= 3 (25.8-83.3% p < 0.001), dementia (3.6-28.6% p < 0.001), osteoporosis (0.0-57.1% p < 0.001), risk of malnutrition (0.0-29.2% p < 0.001) and fracture types (all p < 0.001). All factors were associated with 30- and 90-day mortality. Eight hospitals showed higher and six showed lower 30-day mortality than expected based on their case-mix. Six hospitals showed higher and seven lower 90-day mortality than expected. The specific outlier hospitals changed when correcting for case-mix factors. Conclusions: Dutch hospitals show significant case-mix variation regarding hip fracture patients. Case-mix adjustment is a prerequisite when comparing hospitals' 30-day and 90-day hip fracture patients' mortality. Adjusted mortality may serve as a starting point for improving hip fracture care. Show less
Objective: The aim of the study was to evaluate the oxygen saturation index (OSI) as an early predictor of clinical deterioration in infants with congenital diaphragmatic hernia (CDH). Methods: A... Show moreObjective: The aim of the study was to evaluate the oxygen saturation index (OSI) as an early predictor of clinical deterioration in infants with congenital diaphragmatic hernia (CDH). Methods: A single-center retrospective cohort study was conducted in consecutive infants with isolated CDH with continuous OSI measurements collected in the first 24 h after birth between June 2017 and July 2021. Outcomes of interest were pulmonary hypertension, extracorporeal membrane oxygenation (ECMO)-therapy, and mortality. We evaluated the discriminative values of the maximum OSI value and of mean OSI values with receiver operator characteristic (ROC) analysis and the area under the ROC curve. Results: In 42 infants with 49,473 OSI measurements, the median OSI was 5.0 (interquartile range 3.1-10.6). Twenty-seven infants developed pulmonary hypertension on a median of day 1 (1-1), of which 15 infants had an indication for ECMO-therapy, and 6 infants died. Maximum OSI values were associated with pulmonary hypertension, ECMO-therapy, and mortality. Mean OSI values had an acceptable discriminative ability for pulmonary hypertension and an excellent discriminative ability for ECMO-therapy and mortality. Although OSI measurements were not always present in the first hours after birth, we determined discriminative cut-offs for mean OSI values already in these first hours for pulmonary hypertension, the need for ECMO-therapy, and mortality. Conclusions: Continuous OSI evaluation is a promising modality to identify those infants at highest risk for clinical deterioration already in the first hours after birth. This provides an opportunity to tailor postnatal management based on the individual patient's needs. Show less
Road traffic accidents (RTA) contribute significantly to the global burden of trauma. The World Health Organization indicates that approximately 1.3 million people die each year on the world's... Show moreRoad traffic accidents (RTA) contribute significantly to the global burden of trauma. The World Health Organization indicates that approximately 1.3 million people die each year on the world's roads and between 20 and 50 million sustain non-fatal injuries. The introduction of extensive traffic safety laws, preventive governmental programs and substantial changes in (the organisation of) pre- and in-hospital trauma care have resulted in a gradual decrease in road traffic injuries and fatalities in the 1990s and onward in the Netherlands. Since 2006, however, the number of seriously injured road traffic participants has been increasing despite these government measures to improve road safety. In 2018, an estimated 21,700 people were seriously injured in traffic in the Netherlands, approximately 1,000 more than in 2017.The primary aim of this thesis was to analyse injury patterns, injury severity and mortality for different types of road traffic participants involved in accidents in the Netherlands. Secondly, the association between blood alcohol concentrations, TBI patterns and patient outcome was analysed. Finally, patient and injury characteristics associated with HRQoL, fatigue and societal participation in polytrauma patients were identified. Show less
Objectives: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). Methods: Patients... Show moreObjectives: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). Methods: Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cere-brovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. Results: A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival. Conclusion: The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates. Show less
ObjectivesTo analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE).MethodsPatients... Show moreObjectivesTo analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE).MethodsPatients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders.ResultsA total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29–2.67) and more specifically CVD (HR 2.17, 1.41–3.33) and organic brain syndrome (HR 2.11, 1.19–3.74) accounted as independent prognostic factors for poor survival.ConclusionThe presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates. Show less
Purpose: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are... Show morePurpose: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are unknown. We hypothesize that excess mortality of CSDH patients is related to frailty. In this article, we describe mortality rates and causes of death of CSDH patients compared with the general population and assess the association of frailty with mortality. Methods: A cohort study in which consecutive CSDH patients were compared to the general population regarding mortality rates. Furthermore, the association of six frailty indicators (cognitive problems, frequent falling, unable to live independently, unable to perform daily self-care, use of benzodiazepines or psychotropic drugs, and number of medications) with mortality was assessed. Results: A total of 1307 CSDH patients were included, with a mean age of 73.7 (SD +/- 11.4) years and 958 (73%) were male. Median follow-up was 56 months (range: 0-213). Compared with controls CSDH patients had a hazard ratio for mortality of 1.34 (95% CI: 1.2-1.5). CSDH patients more often died from cardiovascular diseases (37% vs. 30%) and falls (7.2% vs. 3.7%). Among CSDH patients frequent falling (HR 1.3; 95% CI: 1.0-1.7), inability to live independently (HR 1.4, 95% CI: 1.1-1.8), inability to perform daily self-care (HR 1.5; 95% CI: 1.1-1.9), and number of medications used (HR 1.0; 95% CI: 1.0-1.1) were independently associated with mortality. Conclusions: CSDH patients have higher mortality rates than the general population. Frailty in CSDH patients is associated with higher mortality risk. More attention for the frailty of CSDH patients is warranted. Show less
Theuns, D.A.; Verstraelen, T.E.; Lingen, A.C.J. van der; Delnoy, P.P.; Allaart, C.P.; Erven, L. van; ... ; Meeder, J.G. 2022
Background: Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit... Show moreBackground: Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit of ICD therapy with or without cardiac resynchronisation therapy (CRT) in patients with NICMP. In addition, data were compared with real-world clinical data to perform a risk/benefit analysis. Methods: Relevant randomised clinical trials (RCTs) published in meta-analyses since DANISH, and in PubMed, EMBASE and Cochrane databases from 2016 to 2020 were identified. The benefit of ICD therapy stratified by CRT use was assessed using random effects meta-analysis techniques. Results: Six RCTs were included in the meta-analysis. Among patients without CRT, ICD use was associated with a 24% reduction in mortality (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62-0.93; P = 0.008). In contrast, among patients with CRT, a CRT-defibrillator was not associated with reduced mortality (HR: 0.74, 95% CI 0.47-1.16; P = 0.19). For ICD therapy without CRT, absolute risk reduction at 3-years follow-up was 3.7% yielding a number needed to treat of 27. Conclusion: ICD use significantly improved survival among patients with NICMP who are not eligible for CRT. Considering CRT, the addition of defibrillator therapy was not significantly associated with mortality benefit compared with CRT pacemaker. Show less
Introduction: Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms... Show moreIntroduction: Lymph node ratio (LNR) is an important prognostic factor of survival in patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to validate three LNR-based nomograms using an international cohort. Materials and methods: Consecutive PDAC patients who underwent upfront pancreatoduodenectomy from six centers (Europe/USA) were collected (2000-2017). Patients with metastases, R2 resection, missing LNR data, and who died within 90 postoperative days were excluded. The updated Amsterdam nomogram, the nomogram by Pu et al., and the nomogram by Li et al. were selected. For the validation, calibration, discrimination capacity, and clinical utility were assessed. Results: After exclusion of 176 patients, 10113 patients were included. Median overall survival (OS) of the cohort was 23 months (95% CI: 21-25). For the three nomograms, Kaplan-Meier curves showed significant OS diminution with increasing scores (p < 0.01). All nomograms showed good calibration (non-significant Hosmer-Lemeshow tests). For the Amsterdam nomogram, area under the ROC curve (AUROC) for 3-year OS was 0.64 and 0.67 for 5-year OS. Sensitivity and specificity for 3-year OS prediction were 65% and 59%. Regarding the nomogram by Pu et al., AUROC for 3- and 5-year OS were 0.66 and 0.70. Sensitivity and specificity for 3-year OS prediction were 68% and 53%. For the Li nomogram, AUROC for 3- and 5-year OS were 0.67 and 0.71, while sensitivity and specificity for 3-year OS prediction were 63% and 60%. Conclusion: The three nomograms were validated using an international cohort. Those nomograms can be used in clinical practice to evaluate survival after pancreatoduodenectomy for PDAC. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Moderate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in... Show moreModerate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS. Methods: LV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm(2)) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) < 50% (group 1), LVEF >= 50% but LV GLS < 16% (group 2), and LVEF >= 50% and LV GLS >= 16% (group 3). The LV GLS value of 16% was based on spline curve analysis. The primary end point was all-cause mortality. Results: A total of 760 patients (mean age, 71 +/- 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF < 50% and LVEF >= 50% but LV GLS < 16% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (82%, 71%, and 58%; and 92%, 77%, and 58%, respectively) compared with those with LVEF >= 50% and LV GLS >= 16% (96%, 91%, and 85%, respectively; P < .001). Long-term outcomes were not different between patients with LVEF < 50% and those with LVEF >= 50% but LV GLS < 16% (P = .592). LV GLS discriminated higher risk patients even among those with LVEF >= 60% (P < .001) or those who were asymptomatic (P < .001). On multivariable analysis, LVEF < 50% (hazard ratio, 2.384; 95% CI, 1.614-3.522; P < .001) and LVEF >= 50% but LV GLS < 16% (hazard ratio, 2.467; 95% CI, 1.802-3.378; P < .001) were independently associated with all-cause mortality. Conclusions: In patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved. Show less
