Citations

ABSTRACT Rationale Before evidence‐based practice (EBP) was formally adopted, healthcare decisions relied on critical thinking and clinical judgment informed by disciplinary knowledge, theory, and research, but lacked full integration of patient values with clinical expertise. Sackett et al. redefined EBP as the integration of the best available evidence, clinical expertise, and patient values. This framework has been embraced by nursing and other healthcare disciplines, embedding EBP into education, clinical protocols, and quality improvement efforts. Despite widespread adoption, traditional conceptualizations prioritize empirical evidence above patient values, potentially undermining individualized care. Aims and Objectives This paper proposes a reconceptualization that places patient and client values—their why —at the center of EBP, inspired by Simon Sinek's Golden Circle model which emphasizes starting with purpose to influence behavior effectively. Prioritizing the patient's values before incorporating empirical evidence into a care plan ensures that care aligns with their personal goals and definitions of health, fostering therapeutic relationships and supporting meaningful behavior change. Methods A conceptual analysis was conducted using Simon Sinek's Golden Circle model as a guiding framework. This model emphasizes starting with purpose to influence behavior effectively. The analysis explores how integrating patient values first, followed by empirical evidence and clinical expertise, can operationalize person‐centered EBP. Results The reconceptualized framework positions patient values as the foundation of care planning. By aligning interventions with patients' personal goals and values first, clinicians can strengthen therapeutic relationships and support individualized care. Conclusion Effective nursing clinicians and leaders must embrace this patient‐first approach to truly operationalize person‐centered, evidence‐based care that respects the diverse needs and motivations of patients.

Nonmedical stimulant use (NMSU) among adolescents poses significant public health concerns. Using cross-sectional design, this study examined risk and protective factors for NMSU among 20,576 Florida high school students using the 2020 Florida Youth Substance Abuse Survey, with 925 students reporting NMSU. Guided by Hawkins and Catalano’s Social Development Model, we employed multivariate logistic regression analyses to estimate adjusted odds ratios while controlling for demographics. Students engaged in extracurricular activities were 50% less likely to report NMSU. Higher academic performance was associated with lower NMSU likelihood. Students with friends who used stimulants nonmedically were significantly more likely to engage in NMSU (AOR, 7.60; 95% CI: 6.35, 9.10), as were those living with relatives who used substances (AOR, 3.54; 95% CI: 2.94, 4.26). Findings highlight the importance of extracurricular involvement and positive social networks in mitigating NMSU. Interventions addressing family, peers, and extracurricular involvement are crucial for prevention and evidence-based policies.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) µmol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those >2.0 and <5.0 µmol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression. METHODS: We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree. RESULTS: Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42–4.96]; P <0.002). Four main phenotypic branches were identified using unsupervised learning of 3-dimensional shape: (1) nonsarcomeric hypertrophy with coexisting hypertension; (2) diffuse and basal asymmetrical hypertrophy associated with outflow tract obstruction; (3) isolated basal hypertrophy; and (4) milder nonobstructive hypertrophy enriched for familial sarcomeric HCM (odds ratio for pathogenic or likely pathogenic variants, 2.18 [95% CI, 1.93–2.28]; P =0.0001). Polygenic risk for HCM was also associated with different patterns and degrees of disease expression. The model was generalizable to an independent cohort (trustworthiness, M 1 : 0.86–0.88). CONCLUSIONS: We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.

Background: Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. Methods: This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterized cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. Results: Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared with <1% of healthy controls ( P =0.0097). In the London cohort (n=230; median age, 33 years; 84% men), patients were representative of national myocarditis admissions (median age, 32 years; 71% men; 66% case ascertainment), and there was enrichment of rare truncating variants (tv) in ACM-associated genes (3.1% of cases versus 0.4% of controls; odds ratio, 8.2; P =0.001). This was driven predominantly by DSP -tv in patients with normal LV ejection fraction and ventricular arrhythmia. In Maastricht (n=106; median age, 54 years; 61% men), there was enrichment of rare truncating variants in DCM-associated genes, particularly TTN -tv, found in 7% (all with left ventricular ejection fraction <50%) compared with 1% in controls (odds ratio, 3.6; P =0.0116). Across both cohorts over a median of 5.0 years (interquartile range, 3.9–7.8 years), all-cause mortality was 5.4%. Two-thirds of deaths were cardiovascular, attributable to worsening heart failure (92%) or sudden cardiac death (8%). The 5-year mortality risk was 3.3% in genotype-negative patients versus 11.1% for genotype-positive patients ( P adjusted =0.08). Conclusions: We identified DCM- or ACM-associated genetic variants in 8% of patients with acute myocarditis. This was dominated by the identification of DSP -tv in those with normal left ventricular ejection fraction and TTN -tv in those with reduced left ventricular ejection fraction. Despite differences between cohorts, these variants have clinical implications for treatment, risk stratification, and family screening. Genetic counseling and testing should be considered in patients with acute myocarditis to help reassure the majority while improving the management of those with an underlying genetic variant.

Background: Myocarditis may predispose to dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Familial data indicate a potential genetic susceptibility shared with arrhythmogenic cardiomyopathy (ACM). We present the first large-scale genotype-phenotype study of adults with acute myocarditis. Methods: A cohort comprising 336 consecutive patients with acute myocarditis was enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterised cardiomyopathy-associated genes. The burden of rare protein altering variants (PAV) in ACM genes, DCM genes, and TTN specifically, were compared with local healthy controls sequenced on the same platform (n=1053). Case ascertainment was assessed against national hospital admission data. Results: We identified rare protein-altering variants in 23% of cases compared to 16% in controls (Δ+6.8%; p=0.021), with rare truncating variants (tv) in 6% of cases compared to <1% of controls ((Δ+5%; p=0.0097). In London (n=230; median left ventricular ejection fraction (LVEF) 63%), which was representative of national myocarditis admissions, 4.8% of cases carried rare tv, particularly within ACM genes (3% cases vs 0% controls; odds ratio 8.2; p=0.001). This was predominantly driven by desmoplakin (DSP)-tv in patients with normal LVEF. In Maastricht (n=106; median LVEF 30%), rare tv in DCM genes were enriched, particularly TTN-tv found in 7% (all with LVEF<50%) compared to 1% in controls (OR 3.6; p=0.0116). During a median follow-up of 1.9 years, all-cause mortality was greatest in those with a DCM variant (18% vs 4% with no variant; OR 5.0; p=0.004). Conclusion: We identified enrichment of cardiomyopathy gene variants in acute myocarditis patients, dominated by DSP-tv in those with normal LVEF and TTN-tv in those with reduced LVEF. Incorporation of genetic testing may be beneficial to identify such high-risk individuals and guide family screening in acute myocarditis patients.

Abstract We previously identified genomic instability as a causative factor for vascular aging. In the present study, we determined which vascular aging outcomes are due to local endothelial DNA damage, which was accomplished by genetic removal of ERCC1 (excision repair cross-complementation group 1) DNA repair in mice (EC-knockout (EC-KO) mice). EC-KO showed a progressive decrease in microvascular dilation of the skin, increased microvascular leakage in the kidney, decreased lung perfusion, and increased aortic stiffness compared with wild-type (WT). EC-KO showed expression of DNA damage and potential senescence marker p21 exclusively in the endothelium, as demonstrated in aorta. Also the kidney showed p21-positive cells. Vasodilator responses measured in organ baths were decreased in aorta, iliac and coronary artery EC-KO compared with WT, of which coronary artery was the earliest to be affected. Nitric oxide-mediated endothelium-dependent vasodilation was abolished in aorta and coronary artery, whereas endothelium-derived hyperpolarization and responses to exogenous nitric oxide (NO) were intact. EC-KO showed increased superoxide production compared with WT, as measured in lung tissue, rich in endothelial cells (ECs). Arterial systolic blood pressure (BP) was increased at 3 months, but normal at 5 months, at which age cardiac output (CO) was decreased. Since no further signs of cardiac dysfunction were detected, this decrease might be an adaptation to prevent an increase in BP. In summary, a selective DNA repair defect in the endothelium produces features of age-related endothelial dysfunction, largely attributed to loss of endothelium-derived NO. Increased superoxide generation might contribute to the observed changes affecting end organ perfusion, as demonstrated in kidney and lung.