The incidence, mortality and renal outcomes of acute kidney injury in patients with suspected infection at the emergency department

Background Acute kidney injury (AKI) is a major health problem associated with considerable mortality and morbidity. Studies on clinical outcomes and mortality of AKI in the emergency department are scarce. The aim of this study is to assess incidence, mortality and renal outcomes after AKI in patients with suspected infection at the emergency department. Methods We used data from the SPACE-cohort (SePsis in the ACutely ill patients in the Emergency department), which included consecutive patients that presented to the emergency department of the internal medicine with suspected infection. Hazard ratios (HR) were assessed using Cox regression to investigate the association between AKI, 30-days mortality and renal function decline up to 1 year after AKI. Survival in patients with and without AKI was assessed using Kaplan-Meier analyses. Results Of the 3105 patients in the SPACE-cohort, we included 1716 patients who fulfilled the inclusion criteria. Of these patients, 10.8% had an AKI episode. Mortality was 12.4% for the AKI group and 4.2% for the non-AKI patients. The adjusted HR for all-cause mortality at 30-days in AKI patients was 2.8 (95% CI 1.7-4.8). Moreover, the cumulative incidence of renal function decline was 69.8% for AKI patients and 39.3% for non-AKI patients. Patients with an episode of AKI had higher risk of developing renal function decline (adjusted HR 3.3, 95% CI 2.4-4.5) at one year after initial AKI-episode at the emergency department. Conclusion Acute kidney injury is common in patients with suspected infection in the emergency department and is significantly associated with 30-days mortality and renal function decline one year after AKI

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis.

BACKGROUND Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. METHODS For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. FINDINGS The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. INTERPRETATION Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. FUNDING National Institutes of Health and Dr. C.J. Vaillant Fonds

Ambiguous definitions for baseline serum creatinine affect acute kidney diagnosis at the emergency department

Background: Acute kidney injury (AKI) incidence is increasing, however AKI is often missed at the emergency department (ED). AKI diagnosis depends on changes in kidney function by comparing a serum creatinine (SCr) measurement to a baseline value. However, it remains unclear to what extent different baseline values may affect AKI diagnosis at ED. Methods: Routine care data from ED visits between 2012 and 2019 were extracted from the Utrecht Patient Oriented Database. We evaluated baseline definitions with criteria from the RIFLE, AKIN and KDIGO guidelines. We evaluated four baseline SCr definitions (lowest, most recent, mean, median), as well as five different time windows (up to 365 days prior to ED visit) to select a baseline and compared this to the first measured SCr at ED. As an outcome, we assessed AKI prevalence at ED. Results: We included 47,373 ED visits with both SCr-ED and SCr-BL available. Of these, 46,100 visits had a SCr-BL from the − 365/− 7 days time window. Apart from the lowest value, AKI prevalence remained similar for the other definitions when varying the time window. The lowest value with the − 365/− 7 time window resulted in the highest prevalence (21.4%). Importantly, applying the guidelines with all criteria resulted in major differences in prevalence ranging from 5.9 to 24.0%. Conclusions: AKI prevalence varies with the use of different baseline definitions in ED patients. Clinicians, as well as researchers and developers of automatic diagnostic tools should take these considerations into account when aiming to diagnose AKI in clinical and research settings

Virtual pacing of a patient's digital twin to predict left ventricular reverse remodelling after cardiac resynchronization therapy

Aims Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient’s heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. Methods Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were and results retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient’s baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing–induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT’s baseline MWLW-S,DT and virtual pacing–induced ΔMWLW-S,DT were both significantly associated with the real patient’s reverse remodelling ΔLVESV (r = −0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = −0.34, P = 0.02). Conclusion Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery

Cost-effectiveness of screening for chronic hepatitis B and C among migrant populations in a low endemic country.

BACKGROUND: Chronic infection with hepatitis B or C virus (HBV/HCV) can progress to cirrhosis, liver cancer, and even death. In a low endemic country as the Netherlands, migrants are a key risk group and could benefit from early diagnosis and antiviral treatment. We assessed the cost-effectiveness of screening foreign-born migrants for chronic HBV and/or HCV using a societal perspective. METHODS: The cost-effectiveness was evaluated using a Markov model. Estimates on prevalence, screening programme costs, participation and treatment uptake, transition probabilities, healthcare costs, productivity losses and utilities were derived from the literature. The cost per Quality Adjusted Life Year (QALY) gained was estimated and sensitivity analyses were performed. RESULTS: For most migrant groups with an expected high number of chronically infected cases in the Netherlands combined screening is cost-effective, with incremental cost-effectiveness ratios (ICERs) ranging from €4,962/QALY gained for migrants originating from the Former Soviet Union and Vietnam to €9,375/QALY gained for Polish migrants. HBV and HCV screening proved to be cost-effective for migrants from countries with chronic HBV or HCV prevalence of ≥0.41% and ≥0.22%, with ICERs below the Dutch cost-effectiveness reference value of €20,000/QALY gained. Sensitivity analysis showed that treatment costs influenced the ICER for both infections. CONCLUSIONS: For most migrant populations in a low-endemic country offering combined HBV and HCV screening is cost-effective. Implementation of targeted HBV and HCV screening programmes to increase early diagnosis and treatment is important to reduce the burden of chronic hepatitis B and C among migrants

Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination

Background: Integration of a patient’s non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019–10–07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013–11–12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient (ICC) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error (χ2) of LV myocardial strain, strain rate, and cavity volume. Results: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients (χ2 < 1.6), but minimum parameter reproducibility was poor (ICCmin = 0.01). Iterative reduction yielded a reproducible (ICCmin = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs (χ2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). Conclusions: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient’s underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making

Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variants compared with Alpha variant in vaccinated individuals

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared with the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14 to 59 days after complete vaccination compared with ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for reinfection with Beta, Gamma, or Delta variants relative to the Alpha variant in individuals with infection-induced immunity.</p