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Pediatric Takotsubo cardiomyopathy: a review and insights from a national multicentric registry

Abstract Funding Acknowledgements None. Background Takotsubo syndrome (TTS) in the pediatric population is an infrequent but relevant cause of morbidity and mortality, with limited studies addressing its clinical course and prognosis. Objectives We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. Methods we included a total of 54 patients from 4 different hospitals in Spain, as well as pediatric TTS patients from the published literature. Comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between pediatric and adult population features. Results Comparison between the RETAKO general population is detailed in Table 1. Pediatric patients with TTS had a median age of 11 years (IQR = 4-14). When compared to the RETAKO general population, they were more often male (51.9% vs 23.3%, p<0.001), and displayed a higher prevalence of secondary forms (90.7% vs 35.6% in adults, p<0.001). Regarding race, 11 cases (20.4%) were from Asia and 42 (77.8%) were Caucasian; whereas in RETAKO 1420 (94.9%) were Caucasians, with under 5 cases (<0.1%) being Asian. Pediatric patients presented less commonly with angina (11.1% vs 64.1%, p<0.001) or dyspnea (30% vs 41.7%, p<0.001), compared to the general RETAKO cohort. Nevertheless, pediatric patients with TTS exhibited a higher Killip status on admission (Killip IV 74.1% vs 10.5%, p<0.001), and higher needs of vasoactive and mechanical ventilatory support during hospitalization. Regarding complementary exams, pediatric patients presented with lower LVEF on admission (30.5+10.4 vs 36.9+16.9, p = 0.014) together with greater prevalence of atypical (basal or midventricular) TTS patterns on echocardiography (30.2% vs 15.8%, p = 0.006). Additionally, there were significantly less ST-segment alterations in the pediatric population (either ST-segment elevation or depression), without differences on T wave inversion in the admission ECG. During follow-up, all-cause deaths (11.1% vs 12,5%, p = 0.761) and TTS recurrences (3.8% vs 3,8%, p = 0.863) were similar between groups. Conclusions TTS in the pediatric population presents a distinctive clinical profile, with higher prevalence of atypical symptoms and physical triggers; as well as higher rates of cardiogenic shock on admission and similar mortality and recurrence rates than those of the adult population. This study provides valuable insights into understanding pediatric TTS and underscored the necessity for further research in this age group.Table 1

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Reperfusion therapies in patients with intermediate- and high-risk pulmonary embolism: insights from a multicenter registry

Abstract Funding Acknowledgements None. Background Most acute pulmonary embolism (PE) patients receive anticoagulation as a sole treatment. Reperfusion therapies are required in high-risk (HR) and in intermediate-risk (IR)-PE patients with clinical deterioration. Systemic thrombolysis (ST) is the first-line reperfusion therapy, but due to contraindications and major bleeding concerns, catheter-directed therapies (CDT) are rising as a suitable alternative. Purpose The main objective of this study was to look for predictors that lead physicians to decide between different PE therapies in a contemporary cohort of patients. Methods This ambispective registry included consecutive IR- and HR-acute PE patients evaluated by local Pulmonary Embolism Response Team in two tertiary centers from 2014 to 2022. The patients were grouped according to the elected therapy: anticoagulation alone, CDT or ST. If more than one reperfusion therapy was used, the patient was assigned to the group of the first administered therapy. Predictors of reperfusion therapy assignment were evaluated using a logistic regression analysis. Also, early safety outcomes and procedural results after CDT were analyzed. Results A total of 274 patients were included. Of them, 112 received only anticoagulation, 96 received ST as primary treatment, and 66 underwent CDT at first. Baseline characteristics are displayed in Picture 1. Patients in the ST group were significantly younger (p<0.01). Comorbidities were higher in the CDT group compared to the other two. Patients undergoing CDT or ST had higher PE severity parameters at hospital admission than the anticoagulation group (e.g. shock index, RV involvement, or lactate levels; p<0.01 for all). The Pulmonary Embolism Severity Index score, which incorporates comorbidities and PE severity parameters, was higher in CDT patients compared to the other two groups (p<0.01). Picture 2 shows the trend in the choice between the two primary reperfusion therapies over the years. After multivariable analysis, the Charlson comorbidity index, recent surgery and bilateral central PE remained independent predictors for the use of CDT instead of ST (p<0.05 for all). A significant decrease in the systolic and mean pulmonary artery pressure and a significant increase in systolic blood pressure after procedure was detected in patients undergoing CDT. Regarding early safety outcomes, intracranial bleeding occurred only in the ST group. In contrast, the incidence of major bleeding, acute kidney injury and 30-day mortality did not differ between CDT and ST groups. Conclusion This contemporary registry used CDT as primary therapy in 24% of IHR and HR patients, mainly in comorbid and post-surgical patients, and increased over time. CDT was a safe and effective alternative to ST, achieving significant and early improvement in right ventricular function and hemodynamics.Baseline characteristicsChoice of reperfusion therapy over time

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Evolution of economic burden of heart failure by ejection fraction in newly diagnosed patients in Spain

ObjectiveTo describe healthcare resource utilization (HCRU) and costs, in patients with newly diagnosed heart failure (HF) according to ejection fraction (EF) in Spain.MethodsRetrospective cohort study that analyzed anonymized, integrated and computerised medical records in Spain. Patients with ≥ 1 new HF diagnosis between January 2013 and September 2019 were included and followed-up during a 4-year period. Rates per 100 person-years of HCRU and costs were estimated.ResultsNineteen thousand nine hundred sixty-one patients were included, of whom 43.5%, 26.3%, 5.1% and 25.1% had HF with reduced, preserved, mildly reduced and unknown EF, respectively. From year 1 to 4, HF rates of outpatient visits decreased from 1149.5 (95% CI 1140.8–1159.3) to 765.5 (95% CI 745.9–784.5) and hospitalizations from 61.7 (95% CI 60.9–62.7) to 15.7(14.7–16.7) per 100 person-years. The majority of HF-related healthcare resource costs per patient were due to hospitalizations (year 1–4: 63.3–38.2%), followed by indirect costs (year 1–4: 12.2–29.0%), pharmacy (year 1–4: 11.9–19.9%), and outpatient care (year 1–4: 12.6–12.9%). Mean (SD) per patient HF-related costs decreased from 2509.6 (3518.5) to 1234.6 (1534.1) Euros (50% cost reduction). At baseline, 70.1% were taking beta-blockers, 56.3% renin-angiotensin system inhibitors, 11.8% mineralocorticoid receptor antagonists and 8.9% SGLT2 inhibitors. At 12 months, these numbers were 72.3%, 65.4%, 18.9% and 9.8%, respectively.ConclusionsAlthough the economic burden of HF decreased over time since diagnosis, it is still substantial. This reduction could be partially related to a survival bias (sick patients died early), but also to a better HF management. Despite that, there is still much room for improvement.

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PA-450 Laboratory diagnosis of Pneumocystis jirovecii in HIV-positive infants with severe pneumonia using non-invasive samples

BackgroundThe laboratory diagnosis of P. jirovecii pneumonia (PCP) is typically based on microscopic observation of cysts and trophic forms on deep respiratory specimens. In low-income countries, access to bronchoalveolar lavage is limited, particularly for children, and PCP is usually a clinical diagnosis in HIV-positive infants. The use of different laboratory tests on more easily-obtained upper respiratory and venous blood samples could enhance laboratory-confirmed PCP diagnosis.MethodsPCP-PED is an ongoing ancillary-study of the EMPIRICAL trial (#NCT03915366), supported by the EDCTP2 Program and the European Union (TMA2020CDF-3217), which recruits HIV-positive infants hospitalized with severe pneumonia from 8 hospitals in Mozambique. Nasopharyngeal aspirates are processed for direct immunofluorescence microscopy (IFM) to detect P. jirovecii cysts and for quantitative polymerase chain reaction (qPCR) targeting kex-1 gene (Genesig real-time PCR kit). Plasma samples will be used for serologic quantification of (1–3)-β-D-glucan (BG) and Human Krebs Von Den Lungen-6 (KL-6) antigens. ResultsIn interim analysis as of March 2023, 61/151 (40.4%) participants recruited have qPCR and IFM results. Median age was 4.0 [IQR, 3.1–6.3] months and 47.5% (29/61) were female. Median HIV viral load and CD4% were 6.0 logs cp/mL [IQR, 5.9 -6.9] and 13.5% [IQR, 10.0–19.6], respectively. qPCR was positive in 45.9% (28/61) and 39.3% (11/28) were on cotrimoxazole prophylaxis prior to hospitalization. The median P. jirovecii fungal load on positive samples was 13,304 copies/mL [IQR, 3,975–61,484]. Among participants with positive qPCR, 25% (7/28) were IFM positive. All participants with negative qPCR results were IFM negative; no participants with positive IFM had negative qPCR results. ConclusionPositivity rates for qPCR were higher than for IFM, suggesting superior sensitivity for P. jirovecii detection. Future analysis will focus on qPCR/IFM correlation, BG and KL-6 results, and P. jirovecii PCR fungal loads to attempt to differentiate colonization and infection.

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PA-477 Building a national network for inpatient pediatric clinical research in Mozambique

BackgroundUniversidade Eduardo Mondlane (UEM) and Hospital Central de Maputo (HCM) were invited to join a consortium of established pediatric research groups from 5 other sub-Saharan Africa countries in a proposal for the EMPIRICAL trial, which received EDCTP funding in 2019 (RIA2017MC-2013). At that time, HCM and UEM did not have an active pediatric research team, nor a history of collaboration on a pediatric clinical trial. MethodsA research office was established on the HCM pediatric wards. Procurement and laboratory cooperation was established with another Mozambique recruiting site, Centro de Investigação em Saúde de Manhiça. Dedicated and part-time staff were hired, including an HCM pediatrician and nurse. Comprehensive research training was conducted, and the first EMPIRICAL patient was recruited in May 2020. Due to slow recruitment across the consortium, UEM agreed to extend to an additional 3 hospitals in Maputo, again including Ministry of Health staff at each new site. Recruitment was similarly extended to the principal referral/academic hospitals in the other regions of Mozambique with inclusion of Hospital Central de Beira in 2020 and Hospital Central de Nampula in 2021, in partnership with Universidade Católica de Moçambique and Universidade Lúrio. This network has led recruitment in EMPIRICAL, is participating in four pharmacokinetic substudies and an autopsy substudy, and has 2 local ancillary studies, one with EDCTP Career Development Fellowship support (TMA2020CDF-3217).ResultsThe infrastructure and capacity established through EMPIRICAL has been leveraged for additional pediatric inpatient research opportunties, with UEM leading 4 hospitals participating in the EDCTP-funded PediCAP trial (RIA2017MC-2023), and 2 hospitals in the UNITED-meningitis diagnostic study.ConclusionA successful pediatric inpatient research network was quickly established in Mozambique with donor support that facilitated capacity building, and a model that prioritized inclusion of Ministry of Health hospital staff in research teams with inter-institutional collaboration to achieve national coverage.

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PA-455 Bedside ultrasound for the diagnosis of tuberculosis in HIV-positive infants hospitalized with severe pneumonia

BackgroundTuberculosis (TB) diagnosis is challenging in children, particularly in infants, contributing to high TB-related mortality. Up to 30% of infants with pulmonary TB have concurrent extrapulmonary disease, with findings that can frequently be detected with ultrasound. A protocol of focused assessment with sonography for HIV-associated TB (FASH) at six abdominal and thoracic positions has shown promise for diagnosis in children and adults, but few infants have been included in published studies.MethodsEMPIRICAL (#NCT03915366) is a randomized, controlled trial funded by EDCTP (RIA2017MC-2013) recruiting HIV-positive infants <12 months hospitalized with severe pneumonia without current/past TB diagnosis or exposure. All participants have Xpert Ultra (stool, nasopharyngeal aspirate) and urine LAM testing, and in an ongoing blinded diagnostic ancillary study at 5 hospitals in Mozambique, FASH is performed. An interim descriptive analysis was done for participants no longer active in the trial as of April 2023.ResultsFor the 39 participants included, the median age was 3 months (IQR:3.17–5.13), 48.7% were female, and the median CD4% was 13% (IQR:9.90–17.55). There was ≥1 positive FASH finding in 10/39 (25.6%); all had pericardial effusion 10/39 (25.6%), with focal splenic lesions and ascites also noted in 2/39 (5.1%) and 1/39 (2.6%), respectively. No participants had pleural effusion, focal liver lesions, or abdominal lymphadenopathy. In participants with laboratory-confirmed TB, 42.9% (3/7) had ≥1 positive FASH finding. There were 2 positive FASH findings in 7.6% (3/39) participants, of whom 66.7% (2/3) had laboratory-confirmed TB.ConclusionPositive FASH findings were frequent in HIV-positive infants hospitalized with severe pneumonia and even more common in the subset of participants with laboratory-confirmed TB, with pericardial effusion noted on all positive FASH exams. Future analysis will attempt to define which abnormalities on FASH exam are most predictive of TB disease and assess the use of FASH to monitor TB treatment response.

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Differences in healthcare service utilization in patients with polypharmacy according to their risk level by adjusted morbidity groups: a population-based cross-sectional study

BackgroundPatients with polypharmacy suffer from complex medical conditions involving a large healthcare burden. This study aimed to describe the characteristics and utilization of primary care (PC) and hospital care (HC) and factors associated in chronic patients with polypharmacy, stratifying by adjusted morbidity groups (AMG) risk level, sex and age, and comparing with non-polypharmacy.MethodsCross-sectional study conducted in a Spanish basic healthcare area. Studied patients were those over 18 years with chronic diseases identified by the AMG tool from Madrid electronic clinical record, which was the data source. Sociodemographic, sociofunctional, clinical and healthcare utilization variables were described and compared by risk level, sex, age and having or not polypharmacy. Factors associated with healthcare utilization in polypharmacy patients were determined by a negative binomial regression model.ResultsIn the area studied, 61.3% patients had chronic diseases, of which 16.9% had polypharmacy vs. 83.1% without polypharmacy. Patients with polypharmacy (vs. non-polypharmacy) mean age was 82.7 (vs. 52.7), 68.9% (vs. 60.7%) were women, and 22.0% (vs. 1.2%) high risk. Their average number of chronic diseases was 4.8 (vs. 2.2), and 95.6% (vs. 56.9%) had multimorbidity. Their mean number of annual healthcare contacts was 30.3 (vs. 10.5), 25.9 (vs. 8.8) with PC and 4.4 (vs. 1.7) with HC. Factors associated with a greater PC utilization in patients with polypharmacy were elevated complexity, high risk level and dysrhythmia. Variables associated with a higher HC utilization were also increased complexity and high risk, in addition to male sex, being in palliative care, having a primary caregiver, suffering from neoplasia (specifically lymphoma or leukaemia) and arthritis, whereas older age and immobilization were negatively associated.ConclusionsPolypharmacy population compared to non-polypharmacy was characterized by a more advanced age, predominance of women, high-risk, complexity, numerous comorbidities, dependency and remarkable healthcare utilization. These findings could help healthcare policy makers to optimize the distribution of resources and professionals within PC and HC systems, aiming for the improvement of polypharmacy management and rational use of medicines while reducing costs attributed to healthcare utilization by these patients.

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Efficacy of a cardiac rehabilitation program in a municipal sports center compared to the hospital program: randomized controlled trial eCARCEX.

This study aimed to analyze the effects of an outpatient cardiac rehabilitation program in a municipal sports center on functional capacity and adherence to physical exercise - among other variables - compared to an in-hospital program. Randomized clinical trial that included two parallel groups of acute coronary syndrome patients who performed a cardiac rehabilitation program that consisted of moderate physical exercise intervals along with learning healthy habits in a municipal sports center (experimental group) and in a tertiary hospital (control group) between September 2019 and June 2020. We collected the following data: compliance, anthropometrical, clinical, psychological variables, diet and tobacco habits, strength and functional capacity from ergospirometry. Twenty-two patients completed the cardiac rehabilitation program (experimental group=12, control group=10). Significant improvement was observed for cholesterol, the sit-and-stand test, cardiac frequency in VT1 and VT2, and watts in VT1 in the control group, and for HDL-cholesterol, triglycerides, the sit-and-stand test, and frequency, and watts in VT1 in the experimental group. Better achievement was found in the control group for cardiac frequency in VT2 (11.17 vs 2.88 bpm) and in EG for HDL-cholesterol (11.0 vs 0.63 mg/dL). We are unable to determine the effectiveness of the out-of-hospital cardiac rehabilitation program due to a lack of power (high number of withdrawals caused by COVID-19 lockdown). However, the experimented group achieved higher HDL-cholesterol levels, while cardiac frequency in VT2 was higher in the control group.

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Correlation between Health and eHealth Literacy and a Healthy Lifestyle: A Cross-Sectional Study of Spanish Primary Healthcare Patients.

Health literacy and eHealth literacy play a crucial role in improving a community's ability to take care of themselves, ultimately leading to a reduction in disparities in health. Embracing a healthy way of living is vital in lessening the impact of illnesses and extending one's lifespan. This research delves into the link between the health and eHealth literacy levels of individuals accessing primary healthcare services and investigates how this relates to adopting a health-conscious lifestyle. The approach involves a cross-sectional examination carried out at a healthcare facility in the Madrid region of Spain, focusing on adult patients who are in need of primary care nursing services. Health and eHealth literacy and a healthy lifestyle were measured using the Health Literacy Questionnaire (HLQ), the eHealth Literacy Questionnaire (eHLQ), and the "PA100" questionnaire, respectively. Only some of the dimensions of the HLQ and eHLQ were significantly related to a healthy lifestyle, predominantly with a very low or low relationship. Dimension three of the HLQ and dimension five of the eHLQ acquired more importance and were positioned as positive predictors of a healthy lifestyle. This study helps comprehend the relationship between health and eHealth literacy and a healthy lifestyle, which provides information that contributes to understanding the factors that might have a higher impact on lifestyles.

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