Second Data Release from the European Pulsar Timing Array: Challenging the Ultralight Dark Matter Paradigm.

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0} eV≲m≲10^{-23.3} eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3 GeV/cm^{3}.

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015-04 (PANGEA-Breast) study.

BACKGROUND: We evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients. METHODS: HER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed. RESULTS: Fourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon's design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5-32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment. CONCLUSION: Pembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit. TRIAL REGISTRATION: ClinicalTrials.gov and EudraCT (NCT03025880 and 2016-001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

Regulation of cardiac ion channels by transcription factors: Looking for new opportunities of druggable targets for the treatment of arrhythmias.

Cardiac electrical activity is governed by different ion channels that generate action potentials. Acquired or inherited abnormalities in the expression and/or function of ion channels usually result in electrophysiological changes that can cause cardiac arrhythmias. Transcription factors (TFs) control gene transcription by binding to specific DNA sequences adjacent to target genes. Linkage analysis, candidate-gene screening within families, and genome-wide association studies have linked rare and common genetic variants in the genes encoding TFs with genetically-determined cardiac arrhythmias. Besides its critical role in cardiac development, recent data demonstrated that they control cardiac electrical activity through the direct regulation of the expression and function of cardiac ion channels in adult hearts. This narrative review summarizes some studies showing functional data on regulation of the main human atrial and ventricular Na+, Ca2+, and K+ channels by cardiac TFs such as Pitx2c, Tbx20, Tbx5, Zfhx3, among others. The results have improved our understanding of the mechanisms regulating cardiac electrical activity and may open new avenues for therapeutic interventions in cardiac acquired or inherited arrhythmias through the identification of TFs as potential drug targets. Even though TFs have for a long time been considered as 'undruggable' targets, advances in structural biology have led to the identification of unique pockets in TFs amenable to be targeted with small-molecule drugs or peptides that are emerging as novel therapeutic drugs.

Evaluation of a Cooperia oncophora double-domain ASP-based vaccine against Cooperia spp. infections in cattle and sheep.

A double-domain activation-associated secreted protein (dd-Co-ASP) isolated from the bovine small intestinal parasite Cooperia oncophora was previously shown to be an effective vaccine candidate to protect calves against a homologous challenge infection. The aim of this study was to investigate whether the dd-Co-ASP protein, purified from a Belgian C. oncophora isolate, would offer protection against a C. oncophora isolate from the southern hemisphere as well as other Cooperia species such as C. punctata in cattle and C. curticei in sheep. Two vaccination studies were performed, i.e. one in cattle and one in sheep, in which the protective effects of dd-Co-ASP, supplemented with Quil A as an adjuvant, were compared with an adjuvant control. Whereas our results showed a 75 % reduction in Cooperia spp. cumulative faecal egg counts, the results obtained in sheep demonstrated that dd-Co-ASP was ineffective in raising a protective immune response against a C. curticei challenge infection. Even though sequence analysis of the dd-Co-ASP gene revealed restricted sequence heterogeneity in the double domain ASP within and between bovine Cooperia species, the results of the vaccine study suggest that there is sufficient conservation at the protein level to yield cross-protection, holding promise for the development of a general Cooperia vaccine for use in cattle.

¿Cuáles son los conflictos éticos más frecuentes para los internistas españoles? / Which are the most prevalent ethical conflicts for Spanish internists?

Antecedentes y objetivo Los clínicos se enfrentan en su práctica diaria a multitud de conflictos éticos. No hay estudios sobre los tipos de conflictos éticos que se encuentran con más frecuencia y que preocupan más a los clínicos en España. El objetivo de este estudio es describir los conflictos éticos más frecuentes con los que se encuentran los internistas españoles, así como la importancia que los profesionales atribuyen a cada conflicto. Materiales y métodos Estudio observacional transversal a través de una encuesta voluntaria y anónima, dirigida a médicos internistas españoles y distribuida a través de una plataforma ad hoc de la Sociedad Española de Medicina Interna. Resultados Los problemas éticos más frecuentes y relevantes para los internistas españoles son los relacionados con: el final de la vida (decisiones de limitación del esfuerzo terapéutico, uso de tratamientos paliativos, instauración de órdenes de no reanimación cardiopulmonar); los conflictos que se producen en el seno de la relación clínica, bien con familiares o con pacientes, y la toma de decisiones con pacientes incompetentes. Estos resultados son similares a los de otras series anglosajonas y europeas. Los problemas éticos dificultan más la actividad asistencial a los clínicos que perciben con más frecuencia dichos problemas (50,3%) que los que no los perciben (16%). Conclusiones Los conflictos éticos más frecuentes y relevantes entre los internistas españoles son los relacionados con el manejo del final de la vida, seguidos de los derivados de la relación clínica y el manejo de pacientes incompetentes. Es prioritario diseñar programas de formación que permitan abordar y reconocer mejor dichos problemas (AU)

Background and objective Clinicians face a multitude of ethical conflicts in their daily practice. There have been no studies on the types of ethical conflicts encountered most frequently and that are of most concern to clinicians in Spain. The aim of this study is to report the most common ethical conflicts faced by Spanish internists, as well as the importance that the practitioners attribute to each conflict. Materials and Methods Our observational cross-sectional study employed a voluntary and anonymous survey aimed at Spanish medical internists and distributed through an ad hoc platform of the Spanish Society of Internal Medicine. Results The most common and relevant ethical issues for Spanish internists are related to patients’ end of life (decisions limiting therapeutic effort, use of palliative treatments, the establishment of do-not-resuscitate orders), the conflicts arising within the doctor-patient/family relationship, and making decisions with noncompetent patients. These results are similar to those of other English and European series. The ethical problems further complicate the healthcare activity of clinicians who more often notice these problems (50.3%) than those who do not notice them (16%). Conclusions The most common and relevant ethical conflicts among Spanish internists are related to managing patients’ end of life, followed by those related to the doctor-patient relationship and the management of noncompetent patients. It is essential that training programs be designed to better address and recognise these problems (AU)

Which are the most prevalent ethical conflicts for Spanish internists?

BACKGROUND AND OBJECTIVE: Clinicians face a multitude of ethical conflicts in their daily practice. There have been no studies on the types of ethical conflicts encountered most frequently and that are of most concern to clinicians in Spain. The aim of this study is to report the most common ethical conflicts faced by Spanish internists, as well as the importance that the practitioners attribute to each conflict. MATERIALS AND METHODS: Our observational cross-sectional study employed a voluntary and anonymous survey aimed at Spanish medical internists and distributed through an ad hoc platform of the Spanish Society of Internal Medicine. RESULTS: The most common and relevant ethical issues for Spanish internists are related to patients' end of life (decisions limiting therapeutic effort, use of palliative treatments, the establishment of do-not-resuscitate orders), the conflicts arising within the doctor-patient/family relationship, and making decisions with noncompetent patients. These results are similar to those of other English and European series. The ethical problems further complicate the healthcare activity of clinicians who more often notice these problems (50.3%) than those who do not notice them (16%). CONCLUSIONS: The most common and relevant ethical conflicts among Spanish internists are related to managing patients' end of life, followed by those related to the doctor-patient relationship and the management of noncompetent patients. It is essential that training programs be designed to better address and recognise these problems.

Do internists know what limitation of therapeutic effort means?

OBJECTIVES: To ascertain whether internists know what limitation of therapeutic effort (LTE) means and whether training in palliative care affects this understanding. METHODS: A survey was administered to Spanish internists on their knowledge of LTE and training in palliative care. RESULTS: A total of 273 respondents completed the survey (mean age, 42±12 years), 80.2% of whom were associates. Some 23.8% of the respondents identified the complete definition of LTE. The most frequently selected responses were "not starting an active treatment" (85.0%) and "withdrawing an active treatment" (65.9%). Forty-three percent of the respondents lacked training in palliative care, 73.3% considered their level of understanding to be good or very good, 62.3% stated that they became anxious when addressing planning for end-of-life care with a patient, and 81.3% stated that they had experienced some conflict with their LTE decisions. CONCLUSIONS: Only 1 of every 4 internists knew the proper definition of LTE, with no association with the level of training in palliative care.

¿Saben los internistas qué es la limitación del esfuerzo terapéutico? / Do internists know what limitation of therapeutic effort means?

Objetivos Averiguar si los internistas saben qué es la limitación del esfuerzo terapéutico (LET) y si la formación en cuidados paliativos condiciona dicho conocimiento. Métodos Encuesta a los internistas españoles sobre el conocimiento de la LET y la formación en cuidados paliativos. Resultados Se recibieron 273 encuestas; edad media de los que respondieron 42±12 años; el 80,2% eran adjuntos. El 23,8% identificó la definición completa de la LET; las opciones más escogidas fueron «no iniciar un tratamiento activo» (85,0%) y «retirar un tratamiento activo» (65,9%). El 43% carece de formación en cuidados paliativos, el 73,3% considera que su nivel de conocimiento es bueno o muy bueno, al 62,3% le genera ansiedad afrontar la planificación de cuidados al final de la vida con el paciente y el 81,3% ha tenido algún conflicto con sus decisiones de la LET. Conclusiones Solo 1 de cada 4internistas conoce bien la definición de la LET, sin asociación con el grado de formación en cuidados paliativos (AU)

Objectives To ascertain whether internists know what limitation of therapeutic effort (LTE) means and whether training in palliative care affects this understanding. Methods A survey was administered to Spanish internists on their knowledge of LTE and training in palliative care. Results A total of 273 respondents completed the survey (mean age, 42±12 years), 80.2% of whom were associates. Some 23.8% of the respondents identified the complete definition of LTE. The most frecuently selected responses were «not starting an active treatment»(85.0%) and «withdrawing an active treatment» (65.9%). Forty-three percent of the respondents lacked training in palliative care, 73.3% considered their level of understanding to be good or very good, 62.3% stated that they became anxious when addressing planning for end-of-life care with a patient, and 81.3% stated that they had experienced some conflict with their LTE decisions. Conclusions Only 1 of every 4 internists knew the proper definition of LTE, with no association with level of training in palliative care (AU)

Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL.

BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.

Diverse polarization angle swings from a repeating fast radio burst source.

Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.

Which are the most prevalent ethical conflicts for Spanish internists? / ¿Cuáles son los conflictos éticos más frecuentes para los internistas españoles?

BACKGROUND AND OBJECTIVE: Clinicians face a multitude of ethical conflicts in their daily practice. There have been no studies on the types of ethical conflicts encountered most frequently and that are of most concern to clinicians in Spain. The aim of this study is to report the most common ethical conflicts faced by Spanish internists, as well as the importance that the practitioners attribute to each conflict. MATERIALS AND METHODS: Our observational cross-sectional study employed a voluntary and anonymous survey aimed at Spanish medical internists and distributed through an ad hoc platform of the Spanish Society of Internal Medicine. RESULTS: The most common and relevant ethical issues for Spanish internists are related to patients' end of life (decisions limiting therapeutic effort, use of palliative treatments, the establishment of do-not-resuscitate orders), the conflicts arising within the doctor-patient/family relationship, and making decisions with noncompetent patients. These results are similar to those of other English and European series. The ethical problems further complicate the healthcare activity of clinicians who more often notice these problems (50.3%) than those who do not notice them (16%). CONCLUSIONS: The most common and relevant ethical conflicts among Spanish internists are related to managing patients' end of life, followed by those related to the doctor-patient relationship and the management of noncompetent patients. It is essential that training programs be designed to better address and recognise these problems.

Do internists know what limitation of therapeutic effort means? / ¿Saben los internistas qué es la limitación del esfuerzo terapéutico?

OBJECTIVES: To ascertain whether internists know what limitation of therapeutic effort (LTE) means and whether training in palliative care affects this understanding. METHODS: A survey was administered to Spanish internists on their knowledge of LTE and the training in palliative care. RESULTS: A total of 273 respondents completed the survey (mean age, 42±12 years), 80.2% of whom were associates. Some 23.8% of the respondents identified the complete definition of LTE. The most often chosen responses were «not starting an active treatment¼(85.0%) and «withdrawing an active treatment¼ (65.9%). Forty-three percent of the respondents lacked training in palliative care, 73.3% considered their level of understanding to be good or very good, 62.3% stated that they became anxious when addressing the planning for end-of-life care with the patient, and 81.3% stated that they had had some conflict with their LTE decisions. CONCLUSIONS: Only 1 of every 4 internists knew the proper definition for LTE, with no association with the level of training in palliative care.

Seguimiento del hijo de madre con patología tiroidea autoinmune. ¿Qué no debemos cribar? / Follow-up of infants born to mothers with autoinmune thyroid disease. What should not be screened?

Introducción: La patología tiroidea es un problema frecuente en las mujeres embarazadas. Su etiología suele ser autoinmune siendo la tiroiditis de Hashimoto y la enfermedad de Graves las entidades principales. A pesar de las posibles alteraciones hormonales y del paso transplacentario de anticuerpos estimulantes, la realización de un cribado neonatal específico no ha demostrado su utilidad en el neonato. Pacientes y métodos: Estudio prospectivo (noviembre de 2013-diciembre de 2016) de los hijos de madre con patología tiroidea autoinmune nacidos en un hospital universitario nivel III. Los recién nacidos se seleccionaron en maternidad. Se excluyeron los casos de asfixia perinatal. Los datos se recogieron de las historias clínicas de madres y recién nacidos. Resultados: Se incluyeron 191 recién nacidos. El 90% de las madres estaban diagnosticadas de hipotiroidismo autoinmune, de cuyos hijos solo un 5,8% tuvo alguna alteración analítica tratándose de leves ascensos de tirotropina, con normalización al mes de vida, no correlacionándose con los niveles de anti-TPO. Se diagnosticó una hipertirotropinemia transitoria que precisó tratamiento durante el primer año de vida. El 36,8% de los hijos de madre con Graves tuvo algún control analítico alterado en los primeros 7 días de vida, no diagnosticándose ningún caso de hipertiroidismo y solo una hipertirotropinemia transitoria. Conclusiones: La experiencia de nuestro centro en el manejo del cribado neonatal tiroideo muestra un elevado número de controles analíticos con un escaso rendimiento diagnóstico. No encontramos relación entre niveles de anticuerpos anti-TPO y disfunción tiroidea. Apoyamos las recomendaciones de mantener el cribado neonatal universal como única exploración en los hijos de madre hipotiroidea

Introduction: Thyroid dysfunction is a common problem in pregnant women. It is usually of an autoimmune origin, with Hashimotós thyroiditis and Graveś disease being the most common conditions. Although hormonal changes and transplacental antibody transfer may occur, specific neonatal screening has not been shown to be useful. Patients and method: A prospective study of newborns of women with autoimmune thyroid disease born at a level III university hospital (November 2013-December 2016). Neonates were selected during their stay at the maternity. Babies with perinatal asphyxia were excluded. Data were collected from the clinical histories of mothers and newborns. Results: A total of 191 neonates were included. Ninety percent of mothers had been diagnosed with autoimmune hypothyroidism. Only 5.8% of newborns had some laboratory disorder, consisting of slightly increased thyroid-stimulating hormone levels, which returned to normal at the age of one month and did not correlate to thyroid peroxidase antibody levels. Transient hyperthyrotropinemia was diagnosed in one newborn and required thyroxin treatment during the first year of life. Among newborns from mothers with Graveś disease, 36.8% had some abnormal laboratory value during the first 7 days of life, but there were no cases of hyperthyroidism and only one of transient hyperthyrotropinemia. Conclusions: Experience at our hospital in screening of newborns from hypothyroid mothers reveals a high number of laboratory controls with a poor diagnostic yield. No relationship was found between thyroid peroxidase antibody levels and thyroid dysfunction. We support the recommendations to continue testing serum thyroid-stimulating hormone and FT4 levels at 48h of life in newborns of mothers with autoimmune hypothyroidism

Análisis del gasto de bolsillo ante la enfermedad de menores de 5 años según su condición de pobreza en Paraguay / Analysis of out-of-pocket expenses in the face of the disease of children under 5 according to their poverty status in Paraguay

Introducción: Reducir la pobreza, reducir la mortalidad de menores de 5 años (< 5 años) y lograr cobertura universal de salud son parte de los Objetivos de Desarrollo Sostenible (ODS). Objetivo: determinar el gasto de bolsillo de salud (GBS) ante la enfermedad de < 5 años y su inci-dencia económica en los hogares según su condición de pobreza en Paraguay. Material y Método: se analizó la Encuesta Permanente de Hogares del 2014, considerando la defi-nición oficial de pobreza y la referencia de enfermedad o accidente en un trimestre. Se calculó el promedio de GBS por hogar, la incidencia sobre el ingreso monetario trimestral (IM), sobre los sub-sidios estatales por pobreza (IS) y el equivalente de subsistencia o alimentación (EA). Resultados: Entre los hogares no pobres: 41,1% (IC 37,3 a 45,0) tuvo al menos 1 enfermo < 5 años, de los cuales 76,6% (IC 71,5 a 81,0) tuvo GBS, siendo en promedio 223.455 Gs. (DE 37.445). Los medicamentos fueron 68,9% (IC 61,7 a 76,1) del total. La IM fue 1,7% (IC 1,1 a 2,3). Entre los ho-gares pobres: 50,0% (IC 44,7 a 52,2) tuvo al menos 1 enfermo < 5 años, de los cuales 71,2% (IC 64,7 a 76,9) tuvo GBS, siendo en promedio 125.545 Gs. (DE 14.749). Los medicamentos fueron 77,5% (IC 69,2 a 85,7) del total. La IM fue 4,0% (IC 2,3 a 5,8). La IS fue 54,6% (IC 13,0 a 96,2) y el EA fue el equivalente a 7 días de alimentación en promedio (DE 1,5). Conclusión: Ante los retos de los ODS, Paraguay requiere de mayor protección financiera en salud para niñas y niños < 5 años, mediante sinergias de las políticas de reducción de pobreza y de salud. Palabras Clave: gasto de bolsillo de salud, cobertura universal de salud, derecho a la salud, pobreza, menores de 5 años.

Introduction: Reducing poverty, reducing the mortality of children under 5 years (<5 years) and achieving universal health coverage are part of the Sustainable Development Goals (SDGs). Objective: to determine the out-of-pocket health expenditure (GBS) for the disease of <5 years and its economic impact on households according to their poverty status in Para-guay. Material and Method: the 2014 Permanent Household Survey was analyzed, considering the official definition of poverty and the reference of illness or accident in a quarter. The average of GBS per household, the incidence on quarterly monetary income (IM), on state subsidies for poverty (IS) and the equivalent of feeding (EA) were calculated. Results: Among non-poor households: 41.1% (CI 37.3 to 45.0) had at least 1 <5 years ill or injured, of which 76.6% (CI 71.5 to 81.0) had GBS , being on average 223,455 Gs. (DE 37,445). The medications were 68.9% (CI 61.7 to 76.1) of the total. The IM was 1.7% (CI 1.1 to 2.3). Among poor households: 50.0% (CI 44.7 to 52.2) had at least 1 <5 years ill or injured, of which 71.2% (CI 64.7 to 76.9) had GBS, being in average 125,545 Gs. (DE 14,749). The medications were 77.5% (CI 69.2 to 85.7) of the total. The IM was 4.0% (CI 2.3 to 5.8). The IS was 54,6% (IC 13,0 a 96,2) and the EA was the equivalent of 7 days of feeding on av-erage (SD 1.5). Conclusion: Given the challenges of the SDGs, Paraguay requires greater financial protection in health for children under 5 years, through synergies of poverty reduction and health policies. Keywords: out-of-pocket health expenditure, universal health coverage, right to health, pov-erty, children under 5 years.

Follow-up of infants born to mothers with autoinmune thyroid disease. What should not be screened? / Seguimiento del hijo de madre con patología tiroidea autoinmune. ¿Qué no debemos cribar?

INTRODUCTION: Thyroid dysfunction is a common problem in pregnant women. It is usually of an autoimmune origin, with Hashimotós thyroiditis and Graves disease being the most common conditions. Although hormonal changes and transplacental antibody transfer may occur, specific neonatal screening has not been shown to be useful. PATIENTS AND METHOD: A prospective study of newborns of women with autoimmune thyroid disease born at a level III university hospital (November 2013-December 2016). Neonates were selected during their stay at the maternity. Babies with perinatal asphyxia were excluded. Data were collected from the clinical histories of mothers and newborns. RESULTS: A total of 191 neonates were included. Ninety percent of mothers had been diagnosed with autoimmune hypothyroidism. Only 5.8% of newborns had some laboratory disorder, consisting of slightly increased thyroid-stimulating hormone levels, which returned to normal at the age of one month and did not correlate to thyroid peroxidase antibody levels. Transient hyperthyrotropinemia was diagnosed in one newborn and required thyroxin treatment during the first year of life. Among newborns from mothers with Graves disease, 36.8% had some abnormal laboratory value during the first 7 days of life, but there were no cases of hyperthyroidism and only one of transient hyperthyrotropinemia. CONCLUSIONS: Experience at our hospital in screening of newborns from hypothyroid mothers reveals a high number of laboratory controls with a poor diagnostic yield. No relationship was found between thyroid peroxidase antibody levels and thyroid dysfunction. We support the recommendations to continue testing serum thyroid-stimulating hormone and FT4 levels at 48h of life in newborns of mothers with autoimmune hypothyroidism.