Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study

BackgroundBrolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients.MethodsPatients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated including best-corrected visual acuity (BCVA (logMAR)), foveal centre point (FCP (µm)), central subfield retinal thickness (CSRT (µm)) and macular volume (mm³).ResultsSixty-three eyes of 57 patients with nAMD (52.6% females) with a mean (±SD) age of 79.5±6.7 years were included. Mean change of BCVA was −0.02±0.13 logMAR (p=0.322). Significant reductions were recorded for FCP with a mean (±SD) change of −66.79±72.64 µm, −66.76±60.71 µm for CSRT and −0.27±0.24 mm³ for macular volume (all p<0.001). Intraocular inflammation was observed in seven eyes of seven patients, including one case of retinal vasculitis without occlusion.ConclusionsThe results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.

Ion-Solvent Interaction Behaviour of Lithium Perchlorate in N,N-Dimethylacetamide and its Binary Mixtures with 2-Aminoethanol: FTIR Vibrational and NMR Spectroscopy Study

FTIR vibrational spectra and NMR spectra were studied for different electrolytic concentrations of lithium perchlorate (LiClO4) in pure N,N-dimethylacetamide (DMA) and its binary mixtures with 2-amino ethanol (AE) of the different salt concentration ranges from 0.25 to 1.0 M with a molar ratio of LiClO4:AE:DMA (4:4:4). The 13C NMR and FTIR studies have been used to investigate the behaviour of O=C-N deformation vibration and change in chemical shift. Study revealed that the Li+ ions coordinate to the nitrogen atom of NH4 + structure and O of the C=O group of DMA. The interaction between Li+ ions and solvent molecules was confirmed by the carbonyl stretch symmetric ring deformation bands in DMA. From both studies it was found that the intensity increases, band split and chemical shift values of C atom of C=O of amide group also change with the increase in the concentrations of LiClO4 in binary mixtures of AE + DMA, indicating a strong coordination between Li+ ions and DMA.

P1644Personalized screening intervals for measurement of n-terminal pro-b-type natriuretic peptide improve efficiency of prognostication in patients with chronic heart failure

Background Predefined screening intervals and target levels do not account for variations in temporal patterns of biomarkers between individuals, which may hamper their potential use for therapy guidance. Conversely, a personalized screening approach with screening intervals and target levels based on the evolution of biomarkers in individual patients may further improve risk assessment and therapy guidance. Purpose We hypothesize that personalized screening intervals for N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements in patients with chronic heart failure (CHF) maximize information gain on the individual patient's disease progression, while minimizing the number of necessary measurements. We aim to compare such personalized scheduling of NT-proBNP measurements to a predefined fixed scheduling approach. Methods In 263 CHF patients from the Bio-SHiFT study, NT-proBNP was measured trimonthly according to a prespecified, fixed schedule [median: 9 (IQR: 5–10) measurements per patient].The primary composite endpoint (PE) comprised cardiac death, cardiac transplantation, left ventricular assist device implantation or heart failure hospitalization, and occurred in 70 patients (26.6%). Using joint models for time-to-event and longitudinal data, we modelled the association between repeated NT-proBNP measurements and the PE. Using the fitted joint model, for each patient at each follow-up visit, we determined the optimal time point of the next NT-proBNP measurement based on the patient's individual risk profile and the maximum information gain on the patient's prognosis as assessed by the Kullback-Leibler divergence. Personalized scheduling was compared to fixed (trimonthly) scheduling by means of a realistic simulation study, based on a replica of the study population included in the Bio-SHiFT study. In this simulation study, we stopped monitoring NT-proBNP to potentially enable appropriate timely intervention if the cumulative risk of PE exceeded an arbitrary risk threshold of 7.5% within 3-months. We compared personalized scheduling with fixed scheduling in terms of capability of identification of high-risk intervals (whether timely intervention was enabled before occurrence of PE), number of measurements needed, and costs. Results Compared to fixed scheduling, personalized scheduling saved on average 2 measurements [personalized; median: 7 (IQR: 7–8) vs. fixed; 9 (IQR: 8–10) measurements], while the start of the time-window identified for therapeutic intervention to avoid the occurrence of PE was similar in both approaches [personalized; median: 6.6 (IQR: 4.5–11.3) vs. fixed; 6.3 (IQR: 4.2–10.3) months before occurrence of PE]. Costs saved were €165 per patient per year. Figure 1 Conclusion Personalized scheduling of NT-proBNP measurements in CHF patients shows similar prognostic performance as fixed scheduling, but requires fewer NT-proBNP measurements. This may improve efficiency of natriuretic guided therapy, if the latter were to be installed. Acknowledgement/Funding Funding for this study was provided by the Jaap Schouten Foundation and Erasmus MC Efficiency Research grant

How Accurately Can We Recall Food Timing? A Validity Study of a Novel Food Timing Questionnaire (P18-016-19)

Objectives Emerging epidemiological and experimental studies suggest that food timing associates with obesity, weight-loss success, and other adverse cardiometabolic health outcomes. Although anecdotally simple to ascertain, the validity of recalled food timing has not been evaluated against prospectively collected data and current methods do not account for day of the week. Our objective is to validate a novel, recall-based tool, the Eating Pattern Questionnaire (EPQ), aimed at assessing food timing in healthy, free-living populations for work/school days (WD) and non-work days (NWD), against up to 2 weeks of prospectively collected 24-hour food records (FR). Methods A total of 95 participants (72% female; mean age: 33 ± 11 years) from the ongoing Shift Work, Heredity, Insulin, and Food Timing (SHIFT) Study (ClinicalTrials.gov: #NCT02997319) were included. On the EPQ, participants were asked to indicate whether food/beverages are always/sometimes/never consumed during every hour of a WD and NWD (hourly increments). On FR, participants were instructed by trained nutritionists to indicate type and time of all food/beverage items consumed. Food timing was averaged for WD and NWD separately across all completed FR. Five clock times in hour: minute were derived from the two tools: first/last eating episode and breakfast, lunch, and dinner. Concordance was quantified using Kendall's correlation of concordance (W). Results A higher level of concordance was observed for clock time of first eating episode on WD (W = 0.867) compared to NWD (W = 0.568). Clock times for breakfast, lunch, and dinner had comparable concordance on WD and NWD, with highest concordance observed for lunch (WD: W = 1; NWD: W = 0.886), followed by breakfast (WD: W = 0.759; NWD: W = 0.745) then dinner (WD: W = 0.641; NWD: W = 0.665). Lastly, low concordance was found for clock time of the last eating episode for both WD and NWD (WD: W = 0.220; NWD: W = 0.313). Conclusions By comparing clock times estimated from a recall-based questionnaire against prospectively collected food timing data, we observe that individuals may more accurately recall the timing of meals earlier on in the day, particularly on work days, compared to meals later in the evening. These findings provide first insights into the accuracy of food timing data ascertained through self-reported in cohort studies. Funding Sources NIH-R01DK105072.