The purpose of our article is to investigate the impact of symptom experience on health related quality of life (HRQOL) in kidney transplant recipients (KTRs) and whether illness perceptions... Show moreThe purpose of our article is to investigate the impact of symptom experience on health related quality of life (HRQOL) in kidney transplant recipients (KTRs) and whether illness perceptions mediated this impact. Symptom experience, illness perceptions, and HRQOL were measured at transplantation and 6 weeks after transplantation in KTRs in an ongoing Dutch cohort study. Multivariable linear regression models were used for the analysis. 90 KTRs were analyzed. Fatigue and lack of energy were the most prevalent and burdensome symptoms at transplantation. Mental HRQOL at 6 weeks after transplantation was comparable to that of the general Dutch population (mean [standard deviation, SD]: 49.9 [10.7]) versus 50.2 [9.2]), while physical HRQOL was significantly lower (38.9 [9.1] versus 50.6 [9.2]). Experiencing more symptoms was associated with lower physical and mental HRQOL, and the corresponding HRQOL reduced by -0.15 (95%CI, -0.31; 0.02) and -0.23 (95%CI, -0.42; -0.04) with each additional symptom. The identified mediation effect suggests that worse symptom experiences could cause more unhelpful illness perceptions and consequently lead to lower HRQOL. Illness perceptions may explain the negative impact of symptom experience on HRQOL. Future studies at later stages after kidney transplantation are needed to further explore the mediation effect of illness perceptions and guide clinical practice to improve HRQOL. Show less
Steen, W. van der; Ende, N.A.M. van der; Kranendonk, K.R. van; Chalos, V.; Oostenbrugge, R.J. van; Zwam, W.H. van; ... ; MR CLEAN Trial MR CLEAN Registry 2022
BACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location... Show moreBACKGROUND: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location.METHODS: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue.RESULTS: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06-2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02-1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI 1.16-2.78]).CONCLUSIONS: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms.[GRAPHICS]. Show less
Background: X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency disease caused by XIAP gene mutations. A broad range of phenotype, severity, and age at onset... Show moreBackground: X-linked inhibitor of apoptosis (XIAP) deficiency is a rare primary immunodeficiency disease caused by XIAP gene mutations. A broad range of phenotype, severity, and age at onset present challenges for patient management. Objective: We sought to characterize the phenotype, treatment, and survival outcomes of XIAP deficiency and to assess parameters influencing prognosis. Methods: Data published from 2006 to 2020 were retrospectively analyzed. Results: A total of 167 patients from 117 families with XIAP deficiency were reported with 90 different mutations. A wide spectrum of clinical features were seen, of which hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease were the most common. Patients frequently developed multiple features with no clear genotype-phenotype correlation. A total of 117 patients were managed conservatively and 50 underwent hematopoietic stem-cell transplantation (HSCT), with respective overall survival probabilities of 90% and 53% at age 16 years. The predominant indication for HSCT was early-onset HLH. Active HLH and myeloablative conditioning regimens increased HSCT-related mortality, although HSCT outcome was much better after 2015 than before. For conservatively managed patients reaching adulthood, survival probabilities were 86% at age 30 years and 37% by age 52 years, with worse outcomes for patients developing the disease before the age of 5 years or with new disease features in adulthood. Nine asymptomatic mutation carriers with a median age of 13.5 years were identified. Conclusions: Our study demonstrates the variable nature of XIAP deficiency, which evolves over life for individual patients. Better therapeutic strategies and prospective studies are required to reduce morbidity and mortality and improve decision making and long-term outcomes for patients with XIAP deficiency. (J Allergy Clin Immunol 2022;150:456-66.) Show less
Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular... Show moreBackground: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. Methods: The study cohort comprised 1075 children (mean age, 10.2 years [+/- 4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). Results: MLVWT Z score was <10 in 598 (58.1%), >= 10 to <20 in 334 (31.1%), and >= 20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score >= 20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, >= 10 to <20, and >= 20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM. Show less
Wang, Y.M.; Veltkamp, D.M.J.; Boog, P.J.M. van der; Hemmelder, M.H.; Dekker, F.W.; Vries, A.P.J. de; Meuleman, Y. 2022
Background: Medication nonadherence to immunosuppressants is a well-known risk factor for suboptimal health outcomes in kidney transplant recipients (KTRs). This study examined the relationship... Show moreBackground: Medication nonadherence to immunosuppressants is a well-known risk factor for suboptimal health outcomes in kidney transplant recipients (KTRs). This study examined the relationship between illness perceptions and medication nonadherence in prevalent Dutch KTRs and whether this relationship depended on post-transplant time.Methods: Eligible KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. The illness perceptions and medication nonadherence were measured via validated questionnaires. Associations between illness perceptions and medication nonadherence were investigated using multivariable logistic regression models.Results: For the study, 627 participating KTRs were analyzed. 203 (32.4%) KTRs were considered nonadherent to their immunosuppressants with "taking medication more than 2 h from the prescribed dosing time" as the most prevalent nonadherent behaviour (n = 171; 27.3%). Three illness perceptions were significantly associated with medication nonadherence: illness identity (adjusted odds ratio [ORadj] = 1.07; 95% confidence interval [CI], 1.00-1.14), concern (ORadj = 1.07; 95%CI,1.00-1.14), and illness coherence (ORadj = 1.11; 95%CI,1.01-1.22). The relationships between illness perceptions and medication nonadherence did not differ depending on post-transplant time (p-values ranged from 0.48 to 0.96).Conclusion: Stronger negative illness perceptions are associated with medication nonadherence to immunosuppressants. Targeting negative illness perceptions by means of psychoeducational interventions could optimize medication adherence and consequently improve health outcomes in KTRs. Show less
Background and Purpose: Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular... Show moreBackground and Purpose: Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular thrombectomy with older patients. Methods: We used data (March 2014 until November 2017) of patients with an anterior circulation large vessel occlusion stroke from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a nationwide, prospective study on endovascular thrombectomy in the Netherlands. We compared young patients (18-49 years) with older patients (>= 50 years). Outcomes included modified Rankin Scale score after 90 days (both shift and dichotomized analyses), expanded Thrombolysis in Cerebral Infarction score, and symptomatic intracranial hemorrhage. Analyses were adjusted for confounding. Results: We included 3256 patients, 310 (10%) were 18 to 49 years old. Young patients had lower median National Institutes of Health Stroke Scale scores (14 versus 16, P<0.001) and less cardiovascular comorbidities than older patients. Stroke etiologies in young patients included carotid dissection (16%), cardio-embolism (15%), large artery atherosclerosis (10%), and embolic stroke of undetermined source (31%). Clinical outcome was better in young than older patients (acOR for modified Rankin Scale shift: 1.8 [95% CI, 1.5-2.2]; functional independence [modified Rankin Scale score 0-2] 61 versus 39% [adjusted odds ratio, 2.1 [95% CI, 1.6-2.8]); mortality 7% versus 32%, adjusted odds ratio, 0.2 [95% CI, 0.1-0.3]). Symptomatic intracranial hemorrhage occurred less frequently in young patients (3% versus 6%, adjusted odds ratio, 0.5 [95% CI, 0.2-1.00]). Successful reperfusion (expanded Thrombolysis in Cerebral Infarction Score 2b-3) did not differ between groups. Onset to reperfusion time was shorter in young patients (253 versus 255 minutes, adjusted B in minutes 12.4 [95% CI, 2.4-22.5]). Conclusions: Ten percent of patients with acute ischemic stroke undergoing endovascular thrombectomy were younger than 50. Cardioembolism and carotid dissection were common underlying causes in young patients. In one-third of cases, no cause was identified, indicating the need for more research on stroke cause in young patients. Young patients had better prognosis and lower risk of symptomatic intracranial hemorrhage than older patients. Show less
Background. Health-related quality of life (HRQOL) is becoming an increasingly important outcome in kidney transplantation (KT). To describe HRQOL in kidney transplant recipients (KTRs), this... Show moreBackground. Health-related quality of life (HRQOL) is becoming an increasingly important outcome in kidney transplantation (KT). To describe HRQOL in kidney transplant recipients (KTRs), this systematic review summarizes literature that compared HRQOL among KTRs and other relevant populations [i.e. patients receiving dialysis, patients on the waiting list (WL) for KT, patients with chronic kidney disease (CKD) not receiving renal replacement therapy (RRT), the general population (GP) and healthy controls (HCs)] and themselves before KT.Methods. The literature search was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Eligible studies published between January 2000 and October 2020 were included.Results. Forty-four studies comprising 6929 KTRs were included in this systematic review. Despite the study heterogeneity, KTRs reported a higher HRQOL after KT compared with pre-transplantation and compared with patients receiving dialysis with or without being on the WL, especially in disease-specific domains (i.e. burden and effects of kidney disease). Additionally, KTRs had similar to marginally higher HRQOL compared with patients with CKD Stages 3-5 not receiving RRT. When compared with HCs or the GP, KTRs reported similar HRQOL in the first 1 or 2 years after KT and lower physical HRQOL and lower to comparable mental HRQOL in studies with longer post-transplant time.Conclusions. The available evidence suggests that HRQOL improves after KT and can be restored to but not always maintained at pre-CKD HRQOL levels. Future studies investigating intervention targets to improve or maintain post-transplant HRQOL are needed. Show less
Simple Summary Medulloblastoma is rare after puberty. Among several molecular subgroups that have been described, the sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal... Show moreSimple Summary Medulloblastoma is rare after puberty. Among several molecular subgroups that have been described, the sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal population and can be targeted with smoothened (SMO) inhibitors. However, no practice-changing prospective clinical trials have been published in adults to date. Tumors often recur, and treatment toxicity is relevant. Thus, the EORTC 1634-BTG/NOA-23 trial for post-pubertal patients with standard risk medulloblastoma will aim to increase treatment efficacy and to decrease treatment toxicity. Patients will be randomized between standard-dose vs. reduced-dosed radiotherapy, and SHH-subgroup patients will also be randomized between the SMO inhibitor sonidegib (Odomzo(TM,), Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone. In ancillary studies, we will investigate tumor tissue, blood and cerebrospinal fluid samples, magnetic resonance images, and radiotherapy plans to gain information that may improve future treatment. Patients will also be monitored long-term for late side effects of therapy, health-related quality of life, cognitive function, social and professional live outcomes, and reproduction and fertility. In summary, EORTC 1634-BTG/NOA-23 is a unique multi-national effort that will help to council patients and clinical scientists for the appropriate design of treatments and future clinical trials for post-pubertal patients with medulloblastoma. Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy. Treatment toxicity is high and produces disabling long-term side effects. The sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal and adult population and can be targeted by smoothened (SMO) inhibitors. No practice-changing prospective randomized data have been generated in adults. The EORTC 1634-BTG/NOA-23 trial will randomize patients between standard-dose vs. reduced-dosed craniospinal radiotherapy and SHH-subgroup patients between the SMO inhibitor sonidegib (Odomzo(TM), Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone to improve outcomes in view of decreased radiotherapy-related toxicity and increased efficacy. We will further investigate tumor tissue, blood, and cerebrospinal fluid as well as magnetic resonance imaging and radiotherapy plans to generate information that helps to further improve treatment outcomes. Given that treatment side effects typically occur late, long-term follow-up will monitor classic side effects of therapy, but also health-related quality of life, cognition, social and professional outcome, and reproduction and fertility. In summary, we will generate unprecedented data that will be translated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials. Show less
Background and importanceChest pain is one of the most common presentations to the emergency department (ED). The HEART-score is used to assess the 30-day risk of developing a major adverse cardiac... Show moreBackground and importanceChest pain is one of the most common presentations to the emergency department (ED). The HEART-score is used to assess the 30-day risk of developing a major adverse cardiac event (MACE). The HEART-score enables clinicians to classify patients in low, intermediate, or high-risk groups though little is known as to whether this can be done reliably and reproducibly in a prehospital setting.ObjectiveThe aim of this study was to compare the interobserver agreement of the HEART-score between ambulance nurses and ED physicians.Design, settings, and participantsPatients >= 18 years, with chest pain of suspected cardiac origin presented by ambulance to the EDs of four regional hospitals, were prospectively enrolled between October 2018 and April 2019.Outcomes measure and analysisThe primary endpoint was interobserver agreement of the HEART-scores calculated by ambulance nurses compared to those calculated by ED physicians. Agreement was measured using Cohen's Kappa (K) both for overall HEART-score and dichotomized HEART categories. A secondary endpoint was the occurrence of a MACE at 30 days after inclusion.Main resultsA total of 307 patients were enrolled of which 166 patients were male (54%). The mean age was 64.8 years. In 23% (95% confidence interval, 18-27), patients were scored in the low-risk category by both ambulance nurses and ED physicians. The K for the overall HEART-score compared between ambulance nurses and ED physicians was 0.514. The K for the low-risk category versus intermediate and high-risk category was 0.591. Both are defined as 'moderate'. MACE within 30 days occurred in 64 patients (21%). In the low-risk group as defined by the ambulance nurses, there was a 7% risk of MACE compared to an average 5% MACE risk in the ED physician group.ConclusionsThe moderate interobserver agreement of the HEART-score does not currently support the use of the HEART-score by ambulance nurses in a prehospital setting. Training for prehospital nurses is vital to ensure that they are able to calculate the HEART-score accurately. Show less
BackgroundPatients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but... Show moreBackgroundPatients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but data on the emerging risks remain scarce. We assessed the risk for events during the clinical course in adulthood, and provided a novel risk score for event-free survival.Methods and ResultsThis multicenter study observed 167 patients with transposition of the great arteries corrected by an atrial switch operation (61% Mustard procedure; age, 28 [interquartile range, 24-36] years) for 13 (interquartile range, 9-16) years, during which 16 (10%) patients died, 33 (20%) had HF events, defined as HF hospitalizations, heart transplantation, ventricular assist device implantation, or HF-related death, and 15 (9%) had symptomatic ventricular arrhythmias. Five-year risk of mortality, first HF event, and first ventricular arrhythmia increased from 1% each at age 25 years, to 6% (95% CI, 4%-9%), 23% (95% CI, 17%-28%), and 5% (95% CI, 2%-8%), respectively, at age 50 years. Predictors for event-free survival were examined to construct a prediction model using bootstrapping techniques. A prediction model combining age >30 years, prior ventricular arrhythmia, age >1 year at repair, moderate or greater right ventricular dysfunction, severe tricuspid regurgitation, and mild or greater left ventricular dysfunction discriminated well between patients at low (<5%), intermediate (5%-20%), and high (>20%) 5-year risk (optimism-corrected C-statistic, 0.86 [95% CI, 0.82-0.90]). Observed 5- and 10-year event-free survival rates in low-risk patients were 100% and 97%, respectively, compared with only 31% and 8%, respectively, in high-risk patients.ConclusionsThe clinical course of patients undergoing atrial switch increasingly consists of major clinical events, especially HF. A novel risk score stratifying patients as low, intermediate, and high risk for event-free survival provides information on absolute individual risks, which may support decisions for pharmacological and interventional management. Show less
Baumgartner, H.; Backer, J. de; Babu-Narayan, S.V.; Budts, W.; Chessa, M.; Diller, G.P.; ... ; Zeppenfeld, K. 2021
To achieve the ambitious targets for tuberculosis (TB) prevention, care, and control stated by the End TB Strategy, new health care strategies, diagnostic tools are warranted. Host-derived... Show moreTo achieve the ambitious targets for tuberculosis (TB) prevention, care, and control stated by the End TB Strategy, new health care strategies, diagnostic tools are warranted. Host-derived biosignatures are explored for their TB diagnostic potential in accordance with the WHO target product profiles (TPPs) for point-of-care (POC) testing. We aimed to identify sputum-independent TB diagnostic signatures in newly diagnosed adult pulmonary-TB (PTB) patients recruited in the context of a prospective household contact cohort study conducted in Andhra Pradesh, India. Whole-blood mRNA samples from 158 subjects (PTB, n = 109; age-matched household controls, n = 49) were examined by dual-color Reverse-Transcriptase Multiplex Ligation-dependent Probe-Amplification (dcRT-MLPA) for the expression of 198 pre-defined genes and a Mesoscale discovery assay for the concentration of 18 cytokines/chemokines in TB-antigen stimulated QuantiFERON supernatants. To identify signatures, we applied a two-step approach; in the first step, univariate filtering was used to identify and shortlist potentially predictive biomarkers; this step may be seen as removing redundant biomarkers. In the second step, a logistic regression approach was used such that group membership (PTB vs. household controls) became the binary response in a Lasso regression model. We identified an 11-gene signature that distinguished PTB from household controls with AUCs of >= 0.98 (95% CIs: 0.94-1.00), and a 4-protein signature (IFN gamma, GMCSF, IL7 and IL15) that differentiated PTB from household controls with AUCs of >= 0.87 (95% CIs: 0.75-1.00), in our discovery cohort. Subsequently, we evaluated the performance of the 11-gene signature in two external validation data sets viz, an independent cohort at the Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK (GSE107994 data set), and the Catalysis treatment response cohort (GSE89403 data set) from South Africa. The 11-gene signature validated and distinguished PTB from healthy and asymptomatic M. tuberculosis infected household controls in the GSE107994 data set, with an AUC of 0.95 (95% CI: 0.91-0.98) and 0.94 (95% CI: 0.89-0.98). More interestingly in the GSE89403 data set, the 11-gene signature distinguished PTB from household controls and patients with other lung diseases with an AUC of 0.93 (95% CI: 0.87-0.99) and 0.73 (95% CI: 0.56-0.89). These criteria meet the WHO TTP benchmarks for a non-sputum-based triage test for TB diagnosis. We suggest that further validation is required before clinical implementation of the 11-gene signature we have identified markers will be possible. Show less
Background and Purpose:High-serum glucose on admission is a predictor of poor outcome after stroke. We assessed the association between glucose concentrations and clinical outcomes in patients who... Show moreBackground and Purpose:High-serum glucose on admission is a predictor of poor outcome after stroke. We assessed the association between glucose concentrations and clinical outcomes in patients who underwent endovascular treatment.Methods:From the MR CLEAN Registry, we selected consecutive adult patients with a large vessel occlusion of the anterior circulation who underwent endovascular treatment and for whom admission glucose levels were available. We assessed the association between admission glucose and the modified Rankin Scale score at 90 days, symptomatic intracranial hemorrhage and successful reperfusion rates. Hyperglycemia was defined as admission glucose >= 7.8 mmol/L. We evaluated the association between glucose and modified Rankin Scale using multivariable ordinal logistic regression and assessed whether successful reperfusion (extended Thrombolysis in Cerebral Infarction 2b-3) modified this association.Results:Of 3637 patients in the MR CLEAN Registry, 2908 were included. Median admission glucose concentration was 6.8 mmol/L (interquartile range, 5.9-8.1) and 882 patients (30%) had hyperglycemia. Hyperglycemia on admission was associated with a shift toward worse functional outcome (median modified Rankin Scale score 4 versus 3; adjusted common odds ratio, 1.69 [95% CI, 1.44-1.99]), increased mortality (40% versus 23%; adjusted odds ratio, 1.95 [95% CI, 1.60-2.38]), and an increased risk of symptomatic intracranial hemorrhage (9% versus 5%; adjusted odds ratio, 1.94 [95% CI, 1.41-2.66]) compared with nonhyperglycemic patients. The association between admission glucose levels and poor outcome (modified Rankin Scale score 3-6) was J-shaped. Hyperglycemia was not associated with the rate of successful reperfusion nor did successful reperfusion modify the association between glucose and functional outcome.Conclusions:Increased admission glucose is associated with poor functional outcome and an increased risk of symptomatic intracranial hemorrhage after endovascular treatment. Show less
Background and objectives Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system... Show moreBackground and objectives Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort.Design, setting, participants, & measurements We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007-2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment.Results In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases <10%, a 10%-19% increase showed an adjusted hazard ratio (HR) of 1.15 (95% confidence interval [95% CI], 1.05 to 1.27); HR 1.22 (95% CI, 1.07 to 1.40) for 20%-29%; HR 1.55 (95% CI, 1.36 to 1.77) for >= 30%. Similar graded associations were present for heart failure (2275 events, P<0.001) and ESKD (52 events; P<0.001), and, less consistently, myocardial infarction (842 events, P=0.25). Results were robust across subgroups, among continuing users, when patients with decreases in creatinine were excluded from the reference group, and after accounting for death as a competing risk.Conclusions Among real-world monitored adults, increases in creatinine (>10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes. Show less
