Worldwide analysis of actionable genomic alterations in lung cancer and targeted pharmacogenomic strategies.

Based on data from the Global Cancer Statistics 2022, lung cancer stands as the most lethal cancer worldwide, with age-adjusted incidence and mortality rates of 23.6 and 16.9 per 100,000 people, respectively. Despite significant strides in precision oncology driven by large-scale international research consortia, there remains a critical need to deepen our understanding of the genomic landscape across diverse racial and ethnic groups. To address this challenge, we performed comprehensive in silico analyses and data mining to identify pathogenic variants in genes that drive lung cancer. We subsequently calculated the allele frequencies and assessed the deleteriousness of these oncogenic variants among populations such as African, Amish, Ashkenazi Jewish, East and South Asian, Finnish and non-Finnish European, Latino, and Middle Eastern. Our analysis examined 117,707 variants within 86 lung cancer-associated genes across 75,109 human genomes, uncovering 8042 variants that are known or predicted to be pathogenic. We prioritized variants based on their allele frequencies and deleterious scores, and identified those with potential significance for response to anti-cancer therapies through in silico drug simulations, current clinical pharmacogenomic guidelines, and ongoing late-stage clinical trials targeting lung cancer-driving proteins. In conclusion, it is crucial to unite global efforts to create public health policies that emphasize prevention strategies and ensure access to clinical trials, pharmacogenomic testing, and cancer research for these groups in developed nations.

Surface Engineering of Escherichia coli to Display Its Phytase (AppA) and Functional Analysis of Enzyme Activities.

Escherichia coli phytase (AppA) is widely used as an exogenous enzyme in monogastric animal feed mainly because of its ability to degrade phytic acid or its salt (phytate), a natural source of phosphorus. Currently, successful recombinant production of soluble AppA has been achieved by gene overexpression using both bacterial and yeast systems. However, some methods for the biomembrane immobilization of phytases (including AppA), such as surface display on yeast cells and bacterial spores, have been investigated to avoid expensive enzyme purification processes. This study explored a homologous protein production approach for displaying AppA on the cell surface of E. coli by engineering its outer membrane (OM) for extracellular expression. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of total bacterial lysates and immunofluorescence microscopy of non-permeabilized cells revealed protein expression, whereas activity assays using whole cells or OM fractions indicated functional enzyme display, as evidenced by consistent hydrolytic rates on typical substrates (i.e., p-nitrophenyl phosphate and phytic acid). Furthermore, the in vitro results obtained using a simple method to simulate the gastrointestinal tract of poultry suggest that the whole-cell biocatalyst has potential as a feed additive. Overall, our findings support the notion that biomembrane-immobilized enzymes are reliable for the hydrolysis of poorly digestible substrates relevant to animal nutrition.

From Hip Screening to Hip Surveillance: Transforming Care for Patients With Cerebral Palsy: An Analysis of a Single Institution.

INTRODUCTION: Surveillance programs aimed at monitoring hip displacement in patients with cerebral palsy have been demonstrated to decrease the incidence of hip dislocations and properly time surgical intervention, ultimately improving patient outcomes. The objective of this study was to determine whether the implementation of a hip screening to surveillance program at a tertiary academic teaching hospital in 2017 increased the frequency of radiographic evaluations and changed the timing of surgical intervention. METHODS: A total of 592 patients with cerebral palsy were identified, and 468 of these patients had initial radiograph date data available. In this analysis, 246 patients with initial radiograph dates after 2012 were included. The study population was divided into two groups based on the initial radiograph date, 2012 to 2016 versus 2017 to 2022. One hundred sixty patients (65%) were in the 2012 to 2016 group, and 86 (35%) were in the 2017 to 2022 group. Statistical analysis was conducted using various techniques, such as two-sample Student t-test, Mann-Whitney U test, chi square/Fisher exact test, and multivariable linear regression analysis. RESULTS: The average number of radiographs per year in the 2017 to 2022 group was 0.11 (95% CI: 0.02, 0.20, P = 0.017) higher than the 2012 to 2016 group. After adjusting for confounders using multivariable linear regression analysis, this difference was even larger (difference 0.16, 95% CI: 0.06, 0.25, P = 0.001). The surgical intervention rate was significantly lower in the 2017 to 2022 group compared with the 2012 to 2016 group (12.9% versus 40.6%, P < 0.001). DISCUSSION: The results of this study suggest that the implementation of a hip screening to surveillance program results in more frequent radiographic evaluations and possibly a reduced need for surgical intervention from 2017 to 2022. In the 2012 to 2016 group, more surgical interventions were performed likely because of the lack of any hip surveillance or screening program in place.

An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

Transcatheter Tricuspid Annuloplasty in a Patient With Very Long Segment of Right Coronary Artery Proximity.

A 78-year-old woman with severe symptomatic secondary atrial tricuspid regurgitation and a long segment of right coronary artery proximity in the posterior tricuspid annulus was treated with transcatheter annuloplasty. Six consecutive anchors were implanted at the level of the atrial wall, crossing the right coronary artery, achieving residual mild regurgitation. (Level of Difficulty: Advanced.).

Evaluation of an occupational therapy reentry program: Achieving goals to support employment and community living after incarceration.

BACKGROUND: Individuals released from prisons to community supervision often experience unstable housing, unemployment, substance misuse, mental ill-health, and lack of support systems contributing to high rates of recidivism. Occupational therapy practitioners have distinct value in promoting engagement in new habits and routines to support "occupation," or development of daily living skills to support community reentry. OBJECTIVE: We developed an occupational therapy (OT) program within a Department of Corrections (DOC) Community Supervision Center in the Midwest United States. The purpose of this study was to determine feasibility and efficacy of an OT program for community reentry. METHODS: The program was piloted with a sample of five justice-involved men who received OT interventions. Pre- and post-test assessments included a behavioral health interview, demographic survey, five Patient-Reported Outcomes Measurement Information System (PROMIS) assessments, the Vulnerability Index-Service Prioritization Decision Assistance Tool (VI-SPDAT) and Activity Card Sort-Advancing Inclusive Assessment. Descriptive analyses were performed to determine goal attainment and compare pre- and post-test scores over time and to a reference population (PROMIS). Staff of the DOC were also interviewed to assess perceived feasibility and efficacy of this pilot. RESULTS: Significant health changes were reported in participant self-efficacy, managing emotions, anxiety, and sleep disturbances (1 > SD). Moderate changes were seen in reduced feelings of social isolation (0.5 > 1SD). CONCLUSION: It was feasible to implement an OT program with tailored reentry interventions based on unique needs of criminal justice involved individuals. Initial findings suggest OT offers health promotion benefits to reduce risk of recidivism and prepare individuals for community reentry following incarceration.

Prevalence and Prognostic Implications of Moderate or Severe Mitral Regurgitation in Patients with Bicuspid Aortic Valve.

BACKGROUND: Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV. METHODS: In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival. RESULTS: Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. CONCLUSIONS: Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.

Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease.

BACKGROUND: The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied. OBJECTIVES: The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction. METHODS: We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes. RESULTS: The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group). CONCLUSIONS: In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD.

Designing illustrative social media stories to promote adolescent peer support and healthy sexual behaviors.

Objective: Adolescent females in the United States continue to have unmet sexual and reproductive healthcare needs. Research shows that interventions incorporating peer support can augment perceived self-efficacy and reinforce healthy behaviors. Yet, few user-centered digital sexual health interventions incorporate peer support, and aim to change perceptions of peer norms and model social skills. The objective of this study was to design and demonstrate the receptivity of adolescent females to illustrated digital social media stories that promote healthy sexual behaviors and peer social support. Methods: We conducted a three-phase study approved by our Institutional Review Board. In Phase 1, we presented sexually active adolescent female emergency department patients aged 14-19 with eight sexual health scenarios via a survey study. Participants wrote three text messages addressed to the protagonist of each scenario which motivated and encouraged her to consider the use of contraceptives. Messages were scored based on the construct of peer support (emotional, tangible, informational, and belonging). In Phase 2, we worked with a professional artist and screenwriter to design digital sexual health comics using the gathered messages. In Phase 3, we gathered feedback on the comics from adolescent female emergency department patients. Results: Females (n = 22) provided 352 messages. Using top rated messages, we designed five digital visualizations in a running story called Mari tells it like it is. Each story incorporated 5-12 peer-authored quotes. We inserted the final images into Instagram®. Additional females (n = 39) found the images "relatable," "super-realistic," and "educational." Conclusion: Collecting peer-authored texts from our local adolescent community led to the creation of well-received sexual health visualizations. This novel method of design incorporated adolescent voices to promote peer support and healthy behaviors.

PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina.

PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Intranasal ketorolac versus intravenous ketorolac for treatment of migraine headaches in children: A randomized clinical trial.

BACKGROUND: Intravenous ketorolac is commonly used for treating migraine headaches in children. However, the prerequisite placement of an intravenous line can be technically challenging, time-consuming, and associated with pain and distress. Intranasal ketorolac may be an effective alternative that is needle-free and easier to administer. We aimed to determine whether intranasal ketorolac is non-inferior to intravenous ketorolac for reducing pain in children with migraine headaches. METHODS: We conducted a randomized double-blind non-inferiority clinical trial. Children aged 8-17 years with migraine headaches, moderate to severe pain, and requiring parenteral analgesics received intranasal ketorolac (1 mg/kg) or intravenous ketorolac (0.5 mg/kg). Primary outcome was reduction in pain at 60 min after administration measured using the Faces Pain Scale-Revised (scored 0-10). Non-inferiority margin was 2/10. Secondary outcomes included time to onset of clinically meaningful decrease in pain; ancillary emergency department outcomes (e.g. receipt of rescue medications, headache relief, headache freedom, percentage improvement); 24-h follow-up outcomes; functional disability; and adverse events. RESULTS: Fifty-nine children were enrolled. We analyzed 27 children who received intranasal ketorolac and 29 who received intravenous ketorolac. The difference in mean pain reduction at 60 min between groups was 0.2 (95% CI -0.9, 1.3), with the upper limit of the 95% CI being less than the non-inferiority margin. There were no statistical differences between groups for secondary outcomes. CONCLUSIONS: Intranasal ketorolac was non-inferior to intravenous ketorolac for reducing migraine headache pain in the emergency department.

Left ventricular remodelling in bicuspid aortic valve disease.

AIMS: Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction. METHODS AND RESULTS: In this international, multicentre BAV registry, 1345 patients [51.0 (37.0-63.0) years, 71% male] with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS [hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00-1.17, P = 0.046] and AR (HR 1.19 per 25 g/m2, 95% CI 1.11-1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06-2.23, P = 0.024; HR 1.68, 95% CI 1.17-2.42, P = 0.005; HR 1.59, 95% CI 1.03-2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35-4.60, P = 0.004 and HR 3.05, 95% CI 1.71-5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD. CONCLUSIONS: LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD.

A multi-media digital intervention to improve the sexual and reproductive health of female adolescent emergency department patients.

BACKGROUND: Adolescent females presenting to emergency departments (EDs) inconsistently use contraceptives. We aimed to assess implementation outcomes and potential efficacy of a user-informed, theory-based digital health intervention developed to improve sexual and reproductive health for adolescent females in the ED. METHODS: We conducted a pilot-randomized controlled trial of sexually active female ED patients age 14-19 years. Participants were randomized to the intervention Dr. Erica (Emergency Room Interventions to improve the Care of Adolescents) or usual care. Dr. Erica consists of an ED-based digital intervention along with 3 months of personalized and interactive multimedia messaging. We assessed the feasibility, adoption, and fidelity of Dr. Erica among adolescent female users. Initiation of highly effective contraception was the primary efficacy outcome. RESULTS: We enrolled 146 patients; mean (±SD) age was 17.7 (±1.27) years and 87% were Hispanic. Dr. Erica demonstrated feasibility, with high rates of consent (84.4%) and follow-up (82.9%). Intervention participants found Dr. Erica acceptable, liking (98.0%, on Likert scale) and recommending (83.7%) the program. A total of 87.5% adopted the program, responding to at least one text; a total of 289 weblinks were clicked. Dr. Erica demonstrated fidelity; few participants opted out (6.9%) and failed to receive texts (1.4%). Contraception was initiated by 24.6% (14/57) in the intervention and 21.9% (14/64) in the control arms (absolute risk difference [ARD] = 2.7%, 95% confidence interval [CI] = -12.4% to 17.8%). Participants receiving Dr. Erica were more likely to choose a method to start in the future (65.9% [27/41]) than controls (30.0% [15/50]); ARD = 35.9%, 95% CI = 16.6% to 55.1%). CONCLUSIONS: A personalized, interactive digital intervention was feasible to implement, acceptable to female ED patients and demonstrated high fidelity and adoption. This ED-based intervention shows potential to improve contraception decision making.

Caregiver Perceptions of Mental Health and Barriers to and Facilitators of Their Child's Treatment.

OBJECTIVES: Nearly 1 million children visit emergency departments (EDs) annually for mental health crises. Caregivers play a critical role in the outcome of mental illness in their children, yet there is limited research on effective means to engage caregivers in the ED and provide the support they need. Our aim was to determine caregivers' perceptions about mental illness in their children, specifically regarding suicidality and depression, the impact of the children's mental health on the caregiver, and barriers to and facilitators of treatment. METHODS: Guided by qualitative descriptive methodology, we conducted semistructured, open-ended interviews with a purposive sample of English-speaking primary caregivers of children 6 to 17 years old who presented with suicidal ideations or behaviors to 1 urban pediatric ED. Interviews were recorded and transcribed verbatim, and conventional content analysis was performed. RESULTS: The participants (n = 20) were largely single ethnic-racial minority mothers. Content analysis identified 6 categories: caregivers' definitions of mental health, depression, and suicidality; perceived causes of mental illness; difficulty in identification of mental illness; the influence of the mental illness on caregivers; a complex network of communication among involved parties that resulted in the child's ED visit, as well as barriers to and facilitators of treatment. CONCLUSIONS: We identified several categories that encapsulate caregivers' perceptions of mental health and mental illness in their children and its effect on them. Future research should explore how inner-city EDs might partner with schools and trusted community-based organizations to enhance caregiver knowledge, reduce obstacles to care, increase screening for at-risk youth and implement strategies to optimize outcomes for children with depression and suicidal ideations.

A User-Informed, Theory-Based Pregnancy Prevention Intervention for Adolescents in the Emergency Department: A Prospective Cohort Study.

PURPOSE: Female adolescents seeking emergency department (ED) care are at high risk of unintended pregnancy, primarily because of contraceptive nonuse; yet, few ED patients follow up for reproductive care when referred. The objective of this cohort study was to determine the feasibility, acceptability, adoption, fidelity, and potential efficacy of a personalized and interactive ED-based pregnancy prevention mobile health intervention (Emergency Room Interventions to improve the Care of Adolescents [Dr. Erica]). METHODS: We conducted a prospective cohort study with sexually active female ED patients aged 14-19 years who were not using highly effective contraceptives. Dr. Erica consists of a 10-week, automated, two-way texting intervention based on an evidence-based sexual health curriculum, the Social Cognitive Theory, and motivational interviewing techniques. At 12 weeks, we conducted follow-up via online survey and phone call to measure feasibility, acceptability, adoption, fidelity, and preliminary efficacy data (contraception initiation). RESULTS: We screened 209 female ED patients to enroll 42. The average age was 17.5 years (standard deviation ± 1.4); the majority were Hispanic (n = 37, 88%) and had a primary provider (n = 40, 95%). One participant opted out (1/42, 2%), and a total of 35 participants (83%) completed follow-up. Although interactivity diminished with time, 83% of participants (35/42) replied to one or more text. Ninety-four percent of participants (29/31) liked the messages, and 83% (25/30) would recommend the program. Hormonal contraceptives were initiated by 46% of participants (16/35). CONCLUSIONS: Dr. Erica was feasible and acceptable among female adolescent ED patients and demonstrated high fidelity and adoption. The intervention also showed potential to increase highly effective contraceptive use among high-risk females.

Novel Coronavirus Infection in Febrile Infants Aged 60 Days and Younger.

In this case series, we describe the clinical course and outcomes of 7 febrile infants aged ≤60 days with confirmed severe acute respiratory syndrome coronavirus 2 infection. No infant had severe outcomes, including the need for mechanical ventilation or ICU level of care. Two infants had concurrent urinary tract infections, which were treated with antibiotics. Although a small sample, our data suggest that febrile infants with severe acute respiratory syndrome coronavirus 2 infection often have mild illness.

Interobserver Agreement in the Assessment of Clinical Findings in Children with Headaches.

OBJECTIVE: To determine the interobserver agreement of history and physical examination findings in children undergoing evaluation in the emergency department (ED) for headaches. STUDY DESIGN: We conducted a prospective, cross-sectional study of children aged 2-17 years evaluated at 3 tertiary-care pediatric EDs for non-traumatic headaches. Two clinicians independently completed a standardized assessment of each child and documented the presence or absence of history and physical examination variables. Unweighted κ statistics were determined for 68 history and 24 physical examination variables. RESULTS: We analyzed 191 paired observations; median age was 12 years, with 19 (9.9%) children younger than 7 years. Interrater reliability was at least moderate (κ ≥ 0.41) for 41 (60.3%) patient history variables. Eleven (61.1%) of 18 physical examination variables for which κ statistics could be calculated had a κ that was at least moderate. CONCLUSIONS: A substantial number of history and physical examination findings demonstrated at least moderate κ statistic values when assessed in children with headaches in the ED. These variables may be generalizable across different types of clinicians for evaluation of children with headaches. If also found to predict the presence or absence of emergent intracranial abnormalities, the more reliable clinical findings may be helpful in the development of clinical prediction rules or risk stratification models that could be used across settings for children with headaches.

Right ventricle assessment in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

INTRODUCTION: Limited data are available regarding the evaluation of right ventricular (RV) performance in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). OBJECTIVE: To evaluate the prevalence of RV dysfunction in patients with severe AS undergoing TAVI and long-term changes. METHODS: Consecutive patients with severe AS undergoing TAVI from January 2016 to July 2017 were included. RV anatomical and functional parameters were analyzed: RV diameters, fractional area change, tricuspid annular plane systolic excursion (TAPSE), S-wave tissue Doppler of the tricuspid annulus (RV-S'TDI), global longitudinal strain (RV-GLS), and free wall strain (RV-FWS). Preprocedure and 1-year echo were analyzed. RESULTS: Final population included 114 patients, mean age 83.63 ± 6.31 years, and 38.2% women. The prevalence of abnormal RV function was high, variable depending on the parameter that we analyzed, and it showed a significant reduction 1 year after TAVI implantation: 13.9% vs 6.8% (TAPSE < 17mm), P = .04; 26.3% vs 20% (fractional area change < 35%), P = .048; 41.2% vs 29.2% (RV-S'TDI < 9.5cm/s), P = .04; 48.7% vs 39.5% (RV-GLS > [20]), P = .049; and 48.7% vs 28.9% (RV-FWS > [20]), P = .03. Significant differences were noted between patients with low-flow (LF) vs normal-flow (NF) AS in RV dysfunction prevalence as well as in RV function recovery which is less evident in LF compared with NF patients. CONCLUSIONS: RV dysfunction is high among symptomatic AS patients undergoing TAVI, with variable prevalence depending on the echocardiographic parameter used.