Population-based evaluation of the impact of socioeconomic status on clinical outcomes in patients with heart failure in integrated care settings.

INTRODUCTION AND OBJECTIVES: Low socioeconomic status (SES) is associated with poor outcomes in patients with heart failure (HF). We aimed to examine the influence of SES on health outcomes after a quality of care improvement intervention for the management of HF integrating hospital and primary care resources in a health care area of 209 255 inhabitants. METHODS: We conducted a population-based pragmatic evaluation of the implementation of an integrated HF program by conducting a natural experiment using health care data. We included all individuals consecutively admitted to hospital with at least one ICD-9-CM code for HF as the primary diagnosis and discharged alive in Catalonia between January 1, 2015 and December 31, 2019. We compared outcomes between patients exposed to the new HF program and those in the remaining health care areas, globally and stratified by SES. RESULTS: A total of 77 554 patients were included in the study. Death occurred in 37 469 (48.3%), clinically-related hospitalization in 41 709 (53.8%) and HF readmission in 29 755 (38.4%). On multivariate analysis, low or very low SES was associated with an increased risk of all-cause death and clinically-related hospitalization (all Ps <.05). The multivariate models showed a significant reduction in the risk of all-cause death (HR, 0.812; 95%CI, 0.723-0.912), clinically-related hospitalization (HR, 0.886; 95%CI, 0.805-0.976) and HF hospitalization (HR, 0.838; 95%CI, 0.745-0.944) in patients exposed to the new HF program compared with patients exposed to the remaining health care areas and this effect was independent of SES. CONCLUSIONS: An intensive transitional HF management program improved clinical outcomes, both overall and across SES strata.

L-Serine dietary supplementation is associated with clinical improvement of loss-of-function GRIN2B-related pediatric encephalopathy.

Autosomal dominant mutations in GRIN2B are associated with severe encephalopathy, but little is known about the pathophysiological outcomes and any potential therapeutic interventions. Genetic studies have described the association between de novo mutations of genes encoding the subunits of the N-methyl-d-aspartate receptor (NMDAR) and severe neurological conditions. Here, we evaluated a missense mutation in GRIN2B, causing a proline-to-threonine switch (P553T) in the GluN2B subunit of NMDAR, which was found in a 5-year-old patient with Rett-like syndrome with severe encephalopathy. Structural molecular modeling predicted a reduced pore size of the mutant GluN2B-containing NMDARs. Electrophysiological recordings in a HEK-293T cell line expressing the mutated subunit confirmed this prediction and showed an associated reduced glutamate affinity. Moreover, GluN2B(P553T)-expressing primary murine hippocampal neurons showed decreased spine density, concomitant with reduced NMDA-evoked currents and impaired NMDAR-dependent insertion of the AMPA receptor subunit GluA1 at stimulated synapses. Furthermore, the naturally occurring coagonist d-serine restored function to GluN2B(P553T)-containing NMDARs. l-Serine dietary supplementation of the patient was hence initiated, resulting in the increased abundance of d-serine in the plasma and brain. The patient has shown notable improvements in motor and cognitive performance and communication after 11 and 17 months of l-serine dietary supplementation. Our data suggest that l-serine supplementation might ameliorate GRIN2B-related severe encephalopathy and other neurological conditions caused by glutamatergic signaling deficiency.