Enhanced topical paromomycin delivery for cutaneous leishmaniasis treatment: Passive and iontophoretic approaches.

Conventional treatments for cutaneous leishmaniasis, a neglected vector-borne infectious disease, can frequently lead to serious adverse effects. Paromomycin (PAR), an aminoglycoside antibiotic, has been suggested for the topical treatment of disease-related lesions, but even when formulated in high drug-loading dosage forms, presents controversial efficacy. The presence of five ionizable amino groups hinder its passive cutaneous penetration but make PAR an excellent candidate for iontophoretic delivery. The objective of this study was to verify the feasibility of using iontophoresis for cutaneous PAR delivery and to propose a topical passive drug delivery system that could be applied between iontophoretic treatments. For this, in vitro iontophoretic experiments evaluated different application durations (10, 30, and 360 min), current densities (0.1, 0.25, and 0.5 mA/cm2), PAR concentrations (0.5 and 1.0 %), and skin models (intact and impaired porcine skin). In addition, 1 % PAR hydrogel had its penetration profile compared to 15 % PAR ointment in passive transport. Results showed iontophoresis could deliver suitable PAR amounts to dermal layers, even in short times and with impaired skin. Biodistribution assays showed both iontophoretic transport and the proposed hydrogel delivered higher PAR amounts to deeper skin layers than conventional ointment, even though applying 15 times less drug. To our knowledge, this is the first report of PAR drug delivery enhancement by iontophoresis. In summary, the association of iontophoresis with a topical application of PAR gel seems appropriate for improving cutaneous leishmaniasis treatment.

Time optimization in primary care - chronic prescription cost.

INTRODUCTION: Time optimization is a common goal to most health information institutions. In several countries, chronic electronic renewal prescriptions were one of the main focuses when implementing information systems. In Portugal, Electronic Medical Prescription (PEM®) software is used for most electronic prescriptions. This study aims to quantify the time spent in chronic prescription renewal appointments (CPRA) in primary care and its impact in the Portuguese National Health System (SNS). METHODS: Eight general practitioners (GP) were included in the study during February 2022. The average duration of 100 CPRA was obtained. To determine the number of CPRA performed every year, a primary care BI-CSP® platform was used. Using Standard Cost Model and average medical doctor hourly rate in Portugal we estimated CPRA global costs. RESULTS: Each doctor spent on average 1:55 ± 01:07 min per CPRA. There were 8295 GP working in 2022. A total 635 561 CPRA were performed in 2020 and 774 346 in 2021. In 2020, CPRA costs ranged 303 088 ± 179 419€, and in 2021 that number increased to 369 272 ± 218 599€. CONCLUSION: This is the first study to quantify CPRA's real cost in Portugal. A PEM® software update would allow daily savings, ranging from 830€ (± 491€) in 2020 and 1011€ (± 598€) in 2021. That change could allow hiring 8 ± 5 GP in 2020 and 12 ± 7 in 2021.

Clinical outcome of a single procedure cryoballoon ablation for the treatment of atrial fibrillation: A real-world multicenter experience in Portugal.

BACKGROUND: Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) has been growing as an alternative technique, not only in patients with paroxysmal atrial fibrillation (PAF) but also in persistent atrial fibrillation (AF). Cryoballoon ablation has demonstrated encouraging acute and mid-term results. However, data on long-term follow-up of CB-based PVI are scarce. OBJECTIVE: We sought to examine efficacy, safety, and long-term outcomes of CBA in PAF and persistent AF in four Portuguese centers. METHODS: All patients that were treated with the cryoballoon catheter according to routine practices with a second-generation 28-mm CB in four centers were included. This was a retrospective, non-randomized analysis. Patients were followed-up for >12 months and freedom from atrial arrhythmias (AA) was evaluated at the end of follow-up. RESULTS: Four hundred and six patients (57.7±12.4 years, 66% men) participated. AF was paroxysmal in 326 patients (80.2%) and persistent in 80 (19.7%). The mean procedure time duration was 107.7±50.9 min, and the fluoroscopy time was 19.5±9.7 min. Procedural/periprocedural complications occurred in 30 cases (7.3%), being transient phrenic nerve palsy the most frequent incident (2 out of 3 complications). Anatomic variations of the PV were present in 16.1% of cases. At a mean follow-up of 22.0±15.0 months, 310 patients (76.3%) remained in stable sinus rhythm, with at least one AF episode recurrence documented in 98 cases (24.1%). The recurrence rate was 20.5% in the PAF group and 37.8% in the persistent AF group. CONCLUSION: In this multicenter experience, a single CBA procedure resulted in 75.9% freedom from AF at a 22-month follow-up. This technique was demonstrated to be a safe and effective option in experienced centers for the treatment of PAF and PersAF.

Mental health outcomes in Syrian refugees: A systematic review.

BACKGROUND: Syria is the main country of origin for refugees in the world. The prevalence of mental disorders in this population is high, but there is a lack of more comprehensive data on mental health issues in this population. AIM: This study aims to review the literature for mental health outcomes in Syrian refugees. METHODS: We performed a systematic quantitative literature review of original observational studies indexed on the MEDLINE via PubMed, Embase, Web of Science, PsycINFO, LILACS, and SciELO databases with quantitative data reporting mental health outcomes in Syrian refugees. A descriptive analysis was conducted, and the quality of the included studies was assessed using an adaptation from The National Institutes of Health (NIH) quality assessment tool for observational studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. RESULTS: A total of 64 studies were included. The majority were published between 2019 and 2020, and focused on the prevalence of post-traumatic stress disorder (PTSD), depression, and anxiety, with a wide range of variations. Other outcomes were difficulties in the post-migration period and promotive factors for mental health, such as resilience, positive coping strategies, and psychosocial well-being. CONCLUSIONS: High prevalence rates of mental disorders were observed, as well as risk factors for their occurrence. Studies showed a very high variability of prevalence rates and heterogeneity in methodologies. There is a need for research focusing on other determinants and specific necessities for mental health, especially in the post-resettlement period.

Transculturalidade na psicoterapia de orientação analítica: estudo de um caso e revisão de literatura / Transculturality in analytically oriented psychotherapy: a case study and literature reviewc

A cultura representa os sistemas de valores e simbolismos presentes em um grupo social, e sua influência no psiquismo humano é mencionada na literatura psicanalítica desde a obra Totem e Tabu, de Sigmund Freud. Diferenças culturais podem determinar maneiras diversas de sentir e de expressar o sofrimento psíquico, e no que diz respeito à psicoterapia de orientação analítica considera-se fundamental que o terapeuta esteja sensível aos componentes culturais que influenciam a dinâmica psicológica do paciente. O modelo da psicoterapia transcultural propõe a adaptação de alguns elementos, a fim de cumprir esta finalidade. Este relato foi desenvolvido a partir do atendimento de um paciente de origem africana, admitido em uma internação psiquiátrica por uma síndrome psicótica. Procuramos relacionar os elementos transculturais presentes no caso, como particularidades no idioma e crenças culturais, à prática da psicoterapia de orientação analítica neste contexto. Elementos do conflito psíquico, da transferência e vinculação com o terapeuta foram analisados, tendo por base autores psicanalíticos clássicos e contemporâneos. A partir desta análise, discutimos a respeito de elementos teóricos e técnicos relacionados à transculturalidade em psicoterapia. Espera-se que este relato possa auxiliar psicoterapeutas a trabalhar neste contexto.(AU)

Culture represents value systems and symbolisms present in a social group, and its influence on human psyche has been mentioned in psychoanalytic literature since Sigmund Freud's Totem and Tabu. Cultural differences can determine different ways of feeling and expressing mental distress, and with regard to analytical orientation psychotherapy it is considered essential that the therapist be sensitive to cultural components that influence patient's psychic dynamics. The transcultural psychotherapy model proposes the flexibility of some elements in order to fulfill this purpose. This report was developed from the care of a patient of African origin, admitted to a psychiatric hospital for a psychotic syndrome. We sought to relate the cross-cultural elements present in the case, such as language peculiarities and cultural beliefs, to the practice of analytical-oriented psychotherapy in this context. Characteristics of psychic conflict, transference, and attachment to the therapist were analyzed based on classical and contemporary psychoanalytic authors. From this analysis, we discussed theoretical and technical elements related to transculturality in psychotherapy. It is expected that this report can help psychotherapists to work in this context.(AU)

La cultura representa sistemas de valores y simbolismos presentes en un grupo social, y su influencia en la psique humana ha sido mencionada en la literatura psicoanalítica desde Tótem y tabú de Sigmund Freud. Las diferencias culturales pueden determinar diferentes formas de sentir y expresar el malestar mental, y con respecto a la psicoterapia de orientación analítica se considera fundamental que el terapeuta sea sensible a los componentes culturales que influyen en la dinámica psíquica del paciente. El modelo de psicoterapia transcultural propone la flexibilidad de algunos elementos para cumplir con este propósito. Este relato se elaboró ??a partir de la atención de un paciente de origen africano, ingresado en un hospital psiquiátrico por un síndrome psicótico. Buscamos relacionar los elementos transculturales presentes en el caso, como las peculiaridades del lenguaje y las creencias culturales, con la práctica de la psicoterapia de orientación analítica en este contexto. Se analizaron las características del conflicto psíquico, la transferencia y el apego al terapeuta con base en autores psicoanalíticos clásicos y contemporáneos. A partir de este análisis, discutimos elementos teóricos y técnicos relacionados con la transculturalidad en psicoterapia. Se espera que este informe pueda ayudar a los psicoterapeutas a trabajar en este contexto.(AU)

Non-ST Elevation Myocardial Infarction With Occluded Culprit Artery: A Continuum of Mortality Risk Across the Spectrum of Acute Myocardial Infarction.

BACKGROUND: Non-ST segment elevation myocardial infarction (NSTEMI) patients presenting with occluded culprit artery (OCA) may be at higher risk for worse outcomes. We sought to compare in-hospital (IH) mortality between patients presenting with NSTEMI with and without OCA, and ST-segment elevation myocardial infarction (STEMI). METHODS: This retrospective analysis studied 14,037 patients enrolled in the Portuguese National Registry of Acute Coronary Syndromes. Three groups were defined: (A) STEMI (n = 8616); (B) OCA-NSTEMI (n = 1309); and (C) non-OCA NSTEMI (n = 4112). Baseline characteristics, therapeutic strategies, and outcomes were compared. Multivariate analysis was performed to assess the risk of IH all-cause mortality across the prespecified groups. RESULTS: Twenty-four percent of NSTEMI patients presented with OCA. The left circumflex artery was more frequently the culprit artery in group B (12.4% A vs 34.5% B vs 26.0% C; P<.001) and this group was also less likely to receive percutaneous revascularization (95.2% A vs 69.7% B vs 83.2% C; P<.001). The incidence of left ventricular systolic dysfunction was higher in group A and lower in group C (19.9% A vs 12.2% B vs 8.1% C; P<.001). The adjusted risk of IH mortality was significantly higher in group A when compared with group B (3.9% A vs 1.8% B; odds ratio, 2.34; 95% confidence interval, 1.34-4.07; P<.01) and in group B when compared with group C (1.8% B vs 0.9% C; odds ratio, 2.25; 95% confidence interval, 1.17-4.35; P=.02). CONCLUSION: OCA-NSTEMI patients had worse IH outcomes than non-OCA NSTEMI patients and better IH outcomes than STEMI patients, suggesting the existence of a continuum of increased risk of IH mortality across these groups.

Brecha de sexo en la miocardiopatía hipertrófica / The sex gap in hypertrophic cardiomyopathy

INTRODUCCIÓN Y OBJETIVOS: Se han analizado las diferencias por sexo en múltiples enfermedades cardiovasculares. Sin embargo, el impacto en la miocardiopatía hipertrofia (MCH) no está claro. Nuestro objetivo es caracterizar las diferencias en mortalidad total y cardiovascular en función del sexo en un registro de MCH. MÉTODOS: Se incluyó a 1.042 pacientes (el 41% mujeres, n=429) de un registro nacional de MCH. La media de edad al diagnóstico fue 53±16 años y el seguimiento medio, 65±75 meses. Al diagnóstico, las mujeres eran mayores (56±16 frente a 51±15 años; p <0,001), eran más las sintomáticas (el 56,4 frente al 51,7%; p <0,001) y con insuficiencia cardiaca (el 42,0 frente al 24,2%; p <0,001), disfunción diastólica (el 75,2 frente al 64,1%; p = 0,001), insuficiencia mitral moderada/grave (el 33,4 frente al 21,7%; p = 0,003), y tenían cifras más altas de BNP (920 [366-2.412] frente a 487 [170-1.087] mg/dl; p <0,001]. A las mujeres se les realizaron menos pruebas de estrés y resonancia magnética cardiaca. Las mortalidades total (el 8,4 frente al 5,0%; p = 0,026) y cardiovascular (el 5,5 frente al 2,2%; p = 0,004) fueron mayores entre las mujeres. RESULTADOS: La regresión de riesgos proporcionales de Cox mostró que el sexo femenino era un predictor independiente de mortalidad total (HR=2,05; IC95%, 1,11-3,78; p = 0,021) y mortalidad cardiovascular (HR=3,16; IC95%, 1,25-7,99; p = 0,015). Las mujeres sufrieron más muertes por insuficiencia cardiaca (el 2,6 frente al 0,8%; p = 0,024). A pesar de un riesgo similar de muerte súbita cardiaca (MSC), el número de implantes de desfibrilador automático implantable (DAI) fue menor en mujeres (el 10,9 frente al 15,6%; p = 0,032) y, entre los pacientes sin DAI, la MSC fue mayor en las mujeres (el 1,8 frente al 0,4%; p = 0,031). CONCLUSIONES: En este registro, el sexo femenino fue un predictor independiente de muerte total y cardiovascular, más frecuentemente relacionada con insuficiencia cardiaca. A pesar de un riesgo similar de MSC, las mujeres fueron infratratadas con DAI. Estos hallazgos resaltan la necesidad de una mejora en el enfoque clínico para las mujeres con MCH

INTRODUCTION AND OBJECTIVES: Key sex differences have been explored in multiple cardiac conditions. However, sex impact in hypertrophic cardiomyopathy outcome is unclear. We aimed to characterize sex impact in overall and cardiovascular (CV) mortality in a nationwide hypertrophic cardiomyopathy registry. METHODS: We analyzed 1042 adult patients, 429 (41%) women, from a national registry of hypertrophic cardiomyopathy, with mean age at diagnosis 53±16 years and a mean follow-up of 65±75 months. At baseline, women were older (56±16 vs 51±15 years; P <.001), more symptomatic (56.4%, vs 51.7%; P <.001) and had more heart failure (42.0% vs 24.2%. P <.001), diastolic dysfunction (75.2% vs 64.1% P=.001), moderate/severe mitral regurgitation (33.4% vs 21.7%; P=.003), and higher B-type natriuretic peptide levels (920 [366-2412] mg/dL vs 487 [170-1087] mg/dL; P <.001). Women underwent fewer stress tests and cardiac magnetic resonance. RESULTS: Kaplan-Meier survival curves showed higher overall (8.4% vs 5.0%; P=.026) and CV mortality (5.5% vs 2.2%; P=.004) in women. Cox proportional hazard regression showed that female sex was an independent predictor of overall (HR, 2.05; 95%CI, 1.11-3.78; P=.021) and CV mortality (HR, 3.16; 95%CI, 1.25-7.99; P=.015). Women had more heart failure-related death (2.6% vs 0.8%, P=.024). Despite similar sudden cardiac death (SCD) risk, women received fewer implantable cardioverter-defibrillators (10.9% vs 15.6%; P=.032) and, in patients without cardioverter-defibrillators, SCD occurred more commonly in women (1.8% vs 0.4%; P=.031). CONCLUSIONS: In this nationwide registry, female sex was an independent predictor of overall and CV-related death, with more heart failure-related death. Despite similar SCD risk, women were undertreated with implantable cardioverter-defibrillators. These data highlight the need for an improved clinical approach in women with HCM

Dual antiplatelet therapy in myocardial infarction with non-obstructive coronary artery disease - insights from a nationwide registry.

INTRODUCTION AND OBJECTIVES: Dual antiplatelet therapy (DAPT) is a mainstay for myocardial infarction (MI) therapy. However, in patients with myocardial infarction with non-obstructive coronary artery disease (MINOCA), clear recommendations are lacking in the literature. This study aims to identify the cases in which DAPT is currently prescribed at discharge for MINOCA. METHODS: The authors analyzed a cohort of patients from a multicenter national registry enrolling patients who suffered their first MI between 2010 and 2017, and underwent coronary angiography revealing absence of stenosis ≥50%. Individual antithrombotic therapy was identified. A logistic regression analysis was applied to search for predictors of DAPT. RESULTS: From a total of 16 237 patients analyzed, 709 (4.4%) were categorized as MINOCA. Mean age was 64±13 years, 46.3% (n=409) were females. 390 (55.0%) of MINOCA patients were discharged on DAPT. Males (OR 1.67, CI 95 [1.05-2.38], p=0.027), active smokers (OR=1.82, CI 95 [1.05-3.16], p=0.033), previous percutaneous intervention (OR 3.18, CI 95 [1.48-6.81], p=0.003), ST elevation MI (OR 2.70, CI 95 [1.59-4.76], p<0.001) and sinus rhythm at admission (OR=3.94, CI 95 [2.07-7.48], p<0.001) were independent predictors of DAPT use. CONCLUSION: In this nationwide registry, DAPT was prescribed at discharge in 55% of MINOCA patients. Beyond sinus rhythm, the variables presented as independent predictors for DAPT use identify subgroups of patients who are classified as more prone to thrombotic events. The issue of how to handle antithrombotic agents in MINOCA patients is a topic open for discussion.

Predictors of Fabry disease in patients with hypertrophic cardiomyopathy: How to guide the diagnostic strategy?

BACKGROUND: Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors of FD and to define a clinically useful strategy to discriminate FD among HCM. METHODS: Multicenter study including 780 patients with the ESC definition of HCM. FD screening was performed by enzymatic assay in males and genetic testing in females. Multivariate regression analysis identified independent predictors of FD in HCM. A discriminant function analysis defined a score based on the weighted combination of these predictors. RESULTS: FD was found in 37 of 780 patients with HCM (4.7%): 31 with p.F113L mutation due to a founder effect; and 6 with other variants (p.C94S; p.M96V; p.G183V; p.E203X; p.M290I; p.R356Q/p.G360R). FD prevalence in HCM adjusted for the founder effect was 0.9%. Symmetric HCM (OR 3.464, CI95% 1.151-10.430), basal inferolateral late gadolinium enhancement (LGE) (OR 10.677, CI95% 3.633-31.380), bifascicular block (OR 10.909, CI95% 2.377-50.059) and ST-segment depression (OR 4.401, CI95% 1.431-13.533) were independent predictors of FD in HCM. The score ID FABRY-HCM [-0.729 + (2.781xBifascicular block) + (0.590xST depression) + (0.831xSymmetric HCM) + (2.130xbasal inferolateral LGE)] had a negative predictive value of 95.8% for FD, with a cut-off of 1.0, meaning that, in the absence of both bifascicular block and basal inferolateral LGE, FD is a less probable cause of HCM, being more appropriate to perform HCM gene panel than targeted FD screening. CONCLUSION: FD prevalence in HCM was 0.9%. Bifascicular block and basal inferolateral LGE were the most powerful predictors of FD in HCM. In their absence, HCM gene panel is the most appropriate step in etiological study of HCM.

A Cardiac Pseudoaneurysm as a Thromboembolic Source: Acute Visual Loss due to Cardiac Emboli.

Acute visual loss is rarely caused by a heart condition. This manuscript transcribes a case report of a 36-year-old patient with a 2-year history of aortic valve replacement due to bicuspid aortic valve endocarditis that presents to the emergency department with an acute right eye visual loss. After ophthalmologic investigation identified a central retinal artery occlusion, a transthoracic echocardiography was performed to search for a possible cardiac embolus, despite the patient presenting INR values of 2-2.5 for the last year. A mitral-aortic intervalvular fibrosa pseudoaneurysm was identified. A transoesophageal echocardiography was then performed, identifying a small clot logged inside the pseudoaneurysm that protruded to the left ventricle outflow tract. After INR-adjusted warfarin treatment to levels between 3 and 4, the pseudoaneurysm was surgically closed. This is a rare case since the likely source of embolism to the central retinal artery was the thrombus logged inside the pseudoaneurysm despite a standardly accepted therapeutic INR.

The sex gap in hypertrophic cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Key sex differences have been explored in multiple cardiac conditions. However, sex impact in hypertrophic cardiomyopathy outcome is unclear. We aimed to characterize sex impact in overall and cardiovascular (CV) mortality in a nationwide hypertrophic cardiomyopathy registry. METHODS: We analyzed 1042 adult patients, 429 (41%) women, from a national registry of hypertrophic cardiomyopathy, with mean age at diagnosis 53±16 years and a mean follow-up of 65±75 months. At baseline, women were older (56±16 vs 51±15 years; P <.001), more symptomatic (56.4%, vs 51.7%; P <.001) and had more heart failure (42.0% vs 24.2%. P <.001), diastolic dysfunction (75.2% vs 64.1% P=.001), moderate/severe mitral regurgitation (33.4% vs 21.7%; P=.003), and higher B-type natriuretic peptide levels (920 [366-2412] mg/dL vs 487 [170-1087] mg/dL; P <.001). Women underwent fewer stress tests and cardiac magnetic resonance. RESULTS: Kaplan-Meier survival curves showed higher overall (8.4% vs 5.0%; P=.026) and CV mortality (5.5% vs 2.2%; P=.004) in women. Cox proportional hazard regression showed that female sex was an independent predictor of overall (HR, 2.05; 95%CI, 1.11-3.78; P=.021) and CV mortality (HR, 3.16; 95%CI, 1.25-7.99; P=.015). Women had more heart failure-related death (2.6% vs 0.8%, P=.024). Despite similar sudden cardiac death (SCD) risk, women received fewer implantable cardioverter-defibrillators (10.9% vs 15.6%; P=.032) and, in patients without cardioverter-defibrillators, SCD occurred more commonly in women (1.8% vs 0.4%; P=.031). CONCLUSIONS: In this nationwide registry, female sex was an independent predictor of overall and CV-related death, with more heart failure-related death. Despite similar SCD risk, women were undertreated with implantable cardioverter-defibrillators. These data highlight the need for an improved clinical approach in women with HCM.

Circulating Heterophile Antibodies Causing Cardiac Troponin Elevation: An Unusual Differential Diagnosis of Myocardial Disease.

We present the case of a female patient who developed persistently elevated levels of cardiac troponin (cTn) after a previous episode of clinically presumed myocarditis. Extensive investigation concluded that the presence of heterophile antibodies was causing false positive cTn elevation. (Level of Difficulty: Intermediate.).