Hospital acquired anemia is common during admission and can result in increased transfusion and length of stay. Recumbent posture is known to lead to lower hemoglobin measurements. We tested to see if an initiative promoting evening lab draws would lead to higher hemoglobin measurements due to more time in upright posture during the day and evening.We included patients hospitalized on 2 medical units, beginning March 26, 2020 and discharged prior to January 25, 2021. On one of the units, we implemented an initiative to have routine laboratory draws in the evening rather than the morning starting on August 26, 2020. There were 1217 patients on the control unit and 1265 on the intervention unit during the entire study period. First we used a linear mixed-effects model to see if timing of blood draw was associated with hemoglobin level in the pre-intervention period. We then compared levels of hemoglobin before and after the intervention using a difference-in-difference analysis.In the pre-intervention period, evening blood draws were associated with higher hemoglobin compared to morning (0.28; 95% CI, 0.22-0.35). Evening blood draws increased with the intervention (10.3% vs 47.9%, P > 0.001). However, the intervention floor was not associated with hemoglobin levels in difference-in-difference analysis (coefficient of -0.15; 95% CI, -0.51-0.21).While evening blood draws were associated with higher hemoglobin levels, an intervention that successfully changed timing of routine labs to the evening did not lead to an increase in hemoglobin levels.
The crystal structure of the MJ0796 ATP-binding cassette, a member of the o228/LolD transporter family, has been determined at 2.7-Å resolution with MgADP bound at its active site. Comparing this structure with that of the ATP-bound form of the HisP ATP-binding cassette (Hung, L. W., Wang, I. X., Nikaido, K., Liu, P. Q., Ames, G. F., and Kim, S. H. (1998) Nature 396, 703–707) shows a 5-Å withdrawal of a phylogenetically invariant glutamine residue from contact with the γ-phosphate of ATP in the active site. This glutamine is located in a protein segment that links the rigid F1-type ATP-binding core of the enzyme to an ABC transporter-specific α-helical subdomain that moves substantially away from the active site in the MgADP-bound structure of MJ0796 compared with the ATP-bound structure of HisP. A similar conformational effect is observed in the MgADP-bound structure of MJ1267 (Karpowich, N., et al.(2001)Structure, in press), establishing the withdrawal of the glutamine and the coupled outward rotation of the α-helical subdomain as consistent consequences of γ-phosphate release from the active site of the transporter. Considering this subdomain movement in the context of a leading model for the physiological dimer of cassettes present in ABC transporters indicates that it produces a modest mechanical change that is likely to play a role in facilitating nucleotide exchange out of the ATPase active site. Finally, it is noteworthy that one of the intersubunit packing interactions in the MJ0796 crystal involves antiparallel β-type hydrogen bonding interactions between the outermost β-strands in the two core β-sheets, leading to their fusion into a single extended β-sheet, a type of structural interaction that has been proposed to play a role in mediating the aggregation of β-sheet-containing proteins.
The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aimed to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5-12) and youths (ages 12-20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conducted a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes were examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity was confirmed via PCR, serology, or antigen tests, while negativity required negative test results and no related diagnoses. Risk differences revealed higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children faced increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibited elevated risks for anxiety, suicidality, depression, and related symptoms. These findings highlight SARS-CoV-2 infection as a potential contributor to neuropsychiatric risks, emphasizing the importance of research into tailored treatments and preventive strategies for affected individuals.
Introduction: Heart failure with reduced ejection fraction (HFrEF) is a leading cause of morbidity and mortality. However, shortfalls in prescribing of proven therapies, particularly mineralocorticoid receptor antagonist (MRA) therapy, account for several thousand preventable deaths per year nationwide. Electronic clinical decision support (CDS) is a potential low-cost and scalable solution to improve prescribing of therapies. However, the optimal timing and format of CDS tools is unknown. We developed two CDS tools to inform cardiologists of gaps in MRA therapy for patients with HFrEF and without contraindication to MRA therapy: 1) a best practice alert (BPA) that notifies cardiologists at the time of patient visit, and 2) an automated in-basket message that allows for review between visits (Figure). Objective: The BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce CArdiovascular REcommendations for Heart Failure) trial aims to compare the effectiveness of a BPA vs. in-basket message vs. usual care on the primary outcome of MRA prescribing. Methods: This is a pragmatic, cluster-randomized, three-arm intervention trial. Patients are randomized as a cluster at the level of their cardiologist in a 1:1:1 fashion (180 cardiologists included). The primary outcome is MRA prescription at the end of the study period, and secondary outcomes include prescribing of other GDMT, time to prescription, and provider-level changes in prescribing rates. We will require a total of 1,503 patients (501 per arm) to detect 10% improvement in prescribing with 80% power, and estimate a trial duration of 6 months. Implications: To our knowledge, no study has directly compared the efficacy of a BPA vs. in-basket message. If effective, our findings can be rapidly disseminated to improve morbidity and mortality for patients with HFrEF, and can also inform the development of future CDS interventions for other disease states. Trial registration: NCT05275920
Introduction: Guideline-directed medical therapy (GDMT) dramatically improves outcomes in heart failure with reduced ejection fraction (HFrEF). Our goal was to examine GDMT use in community patients with newly diagnosed HFrEF. Methods: We performed a population-based, retrospective cohort study of all Olmsted County, Minnesota residents with newly diagnosed HFrEF (EF≤40%) 2007-2017. We excluded patients with contraindications to medication initiation (allergy, intolerance, heart rate<50 for beta blockers, SBP <80mm Hg for beta blockers, ACEi/ARB/ARNI; high creatinine (>3 mg/dL ACEi/ARB/ARNI, >2.5 men or >2.0 mg/dL women for mineralocorticoid receptor antagonists, MRAs) or hyperkalemia (potassium >5 meQ/L for ACEi/ARB/ARNI, MRA). We examined use and peak dose achieved for beta blockers, HF beta blockers (metoprolol succinate, carvedilol, bisoprolol), ACEi/ARB/ARNI, and MRA in the first year after HFrEF diagnosis. We used logistic regression to evaluate predictors of GDMT use. Results: From 2007-2017, 1160 patients were diagnosed with HFrEF (mean age 69.7 years, 65.6% men). Most eligible patients received beta blockers (92.1%) and ACEi/ARB/ARNI (86.5%) in the first year after HFrEF. However, only 63.6% of patients were treated with a HF beta blocker, and most did not receive MRAs (82.6%). The percentage of treated patients reaching medication target doses was 20.5% for HF beta blockers, 25.3% for ACEi/ARB/ARNI, and 11.2% for MRA. Compared to patients not seen in an HF clinic, patients seen in an HF clinic (n=380, 32.8%) were at greater odds of receiving beta blockers (OR 3.85, 95% CI 1.79-8.33); HF beta blockers (OR 3.85, 95% CI 2.63-5.26); ACEi/ARB/ARNIs (OR 3.85, 95% CI 2.17-6.67); and MRAs (OR 3.03, 95% CI 2.08-4.35). Other independent predictors of GDMT use included younger age (beta blockers, ACEi/ARB/ARNI), male gender (MRAs), higher SBP (beta blockers, ACEi/ARB/ARNI), lower EF (HF beta blockers), higher BMI (MRAs), and diabetes (ACEi/ARB/ARNI, p<0.05 for each). Conclusions: In this population-based study, most patients with newly diagnosed HFrEF received beta blockers and ACEi/ARB/ARNIs, but goal doses were usually not achieved. GDMT use was much higher in patients referred to an HF clinic.
People with memory disorders have difficulty adhering to treatments. With technological advances, it remains important to investigate the potential of health information technology (HIT) in supporting medication adherence among them.
