Vitamin D supplementation as a rational pharmacological approach in the COVID-19 pandemic.

The COVID-19 pandemic has reached most of the countries worldwide causing death, which often results from an inflammatory storm associated with severe acute respiratory syndrome (SARS). This has prompted researchers to seek specific novel and definitive treatments urgently. In this context, it is interesting to evaluate the preventive and therapeutic effects of existing pharmacological agents that could be useful. In this regard, vitamin D supplementation, particularly in individuals likely to be deficient, may be a promising option. Vitamin D is a hormone that modulates many of the same inflammatory and oxidative signaling pathways triggered during COVID-19. For example, vitamin D suppresses the actions of the renin-angiotensin system, which has a determining role in the pathophysiology of the inflammatory response related to COVID-19. This paper analyzes the evidence that vitamin D supplementation might be a valuable preventive/therapeutic measure in groups at risk for or infected with COVID-19. It also discusses how clinical studies could be best designed to evaluate the possible advantages of vitamin D supplementation for the benefit of public health during the pandemic.

[Health working conditions and environment: conceptual model for remote and rural areas]. / Condiciones y medio ambiente de trabajo en salud: modelo conceptual para áreas remotas y rurales.

This report proposes a conceptual model on workplace environment and working conditions that integrates the available evidence to facilitate the design and evaluation of interventions aimed at improving the attraction, recruitment and retention of health personnel at the first level of care in rural and remote areas. Theoretical, empirical and testimonial evidence was consulted to support the model, and 15 frameworks disseminated in the last 20 years were synthesized. The article shows the diversity of perspectives and the complexity involved in establishing the dimensions to be considered in a proposal that is useful to apply to human resources for health policies.The proposed model includes four categories of components: factors of the external context, organizational factors, employment and work conditions, and individual factors. The boundaries between the components -as well as the weight and influence of each one- vary according to the interrelationship among them and the interaction with the environment, and thus its interpretation must be adapted to the context in which it is intended to be applied.Based on this conceptual model, the design and evaluation of interventions aimed at increasing the availability of health personnel -particularly at the primary care level in rural and remote areas of the Region of the Americas- should emerge from an interaction between health and employment policies, and the realities and expectations of workers and the communities.

[Factors and interventions that affect working conditions and environment to increase the attraction, recruitment and retention of human resources for health at the primary care level in rural, remote or underserved areas]. / Factores e intervenciones que inciden en las condiciones y medio ambiente de trabajo para incrementar la atracción, captación y retención de recursos humanos en salud en el primer nivel de atención de áreas rurales, remotas o desatendidas.

OBJECTIVE: To identify and systematize available empirical evidence on factors and interventions that affect working conditions and environment in order to increase the attraction, recruitment and retention of human resources for health at the primary care level in rural, remote or underserved areas. METHODS: Rapid review of reviews selected according to relevance, eligibility and inclusion criteria. The search was conducted on electronic and manual databases, including grey literature. AMSTAR I was used to assess the quality of systematic reviews and a thematic analysis for synthesis of the results. RESULTS: Sixteen reviews were included, one of which contained 14 reviews. Of the total, 20 reviews analyzed factors and 9 evaluated the effectiveness of interventions. The evidence on factors is abundant, but of limited quality. Individual, family and "previous exposure to a rural setting" factors were associated with higher recruitment; organizational and external context factors were important for human resource retention. Networking and professional support influenced recruitment and retention. Evidence on the effectiveness of interventions was limited, both in quantity and quality. The most frequently used intervention was incentives. CONCLUSIONS: Evidence on factors that are positively related to recruitment and retention of workers at the first level of care in rural, remote or underserved areas is sufficient and should be taken into account when designing interventions. Quality evidence on the effectiveness of interventions is scarce. More controlled studies with methodological rigor are needed, particularly in the Americas.

Analysis of long COVID in health personnel: comparing gender and work factors.

INTRODUCTION: This study aimed to describe the reported prevalence of post-COVID-19 syndrome and its characteristics by gender, profession, and other determinants among health care workers. METHODS: A cross-sectional study was conducted among health workers with a history of COVID-19 in Latin America, and the 2030 responses from Argentina were selected for this analysis. Sociodemographic information, as well as data on initial course of COVID-19, and the persistence of 21 symptoms beyond the first month, their severity, clinical evolution, and health care demands were collected. RESULTS: The reported prevalence of post-COVID-19 syndrome was higher in women for each of the symptom clusters studied. Severity of the initial symptoms, female gender, nursing profession, multi-employment, and working in emergency areas were all independent variables. DISCUSSION: The greater strain of health care workers during the pandemic -highly feminized- and the associated gender conditions may partially explain these findings.

Introducción: El objetivo del estudio fue describir la prevalencia del reporte de síndrome post-COVID-19 y sus características según género, profesión y otros determinantes sociales, en personal de salud. Métodos: Se realizó un estudio de corte transversal en profesionales de salud con antecedentes de COVID-19 en América Latina, y para este análisis se seleccionaron las 2030 respuestas de Argentina. Se recolectaron datos sociodemográficos, información sobre el curso inicial de la enfermedad COVID-19, y persistencia de 21 síntomas más allá del primer mes, su gravedad, evolución clínica y requerimiento de servicios de salud. Resultados: Se identificó que la prevalencia reportada de síndrome post-COVID-19 fue mayor en mujeres para cada uno de los grupos de síntomas explorados. La gravedad del cuadro inicial, el género femenino, la profesión de enfermería, el multiempleo y trabajar en áreas de emergencia fueron variables independientes. Discusión: La mayor sobrecarga del personal de salud durante la pandemia ­altamente feminizado­ y las determinaciones de género asociadas podrían explicar parcialmente estos hallazgos.

Post COVID-19 syndrome. Severity and evolution in 4673 health care workers.

BACKGROUND: The evolution of post COVID syndrome has been variable and we lack information on its impact on healthcare professionals, particularly in Latin America. METHODS: We conducted a survey through a social network in health professionals on post COVID-19 syndrome cases confirmed with PCR. In a web-based questionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work. RESULTS: 4673 health professionals from 21 countries responded, mean age of 47.8 years, 64.2% women. The initial course was asymptomatic in 9.1%, mild symptoms 36.8%, moderate symptoms without hospitalization 40.8% or with hospitalization 11.7%, and severe symptoms with respiratory assistance 1.6%. The most prevalent symptoms were fatigue (67%), insomnia (44.2%), anxiety (42.3%), myalgia (41.9%) and anosmia (41.2%). Considering only severe symptoms (grades 3-4 on a subjective index from 1 to 4), the most prevalent were slowness (36.3%), impaired concentration (33.1%), anosmia (20.4%), fatigue (19.1%), impaired memory (18.1%) and dyspnea (15.9%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the multivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7.8%, related to older age, number of symptoms and severity of the initial course. CONCLUSION: In conclusion, in many cases the persistence of post-COVID symptoms can be prolonged and have an occupational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.

Introducción: La evolución del síndrome post COVID ha sido variable y carecemos de información sobre su impacto en los profesionales de la salud. Métodos: Realizamos una encuesta a través de una red social en profesionales de la salud sobre casos de síndrome post COVID-19 confirmados con PCR. En un cuestionario web, preguntamos sobre 21 síntomas, su gravedad, duración, grado de afectación de la actividad y reincorporación al trabajo. Resultados: Respondieron 4673 profesionales sanitarios de 21 países, edad media de 47 años, 64% mujeres. El curso inicial fue asintomático en el 9%, síntomas leves en el 36%, síntomas moderados sin hospitalización en el 40% o con hospitalización en el 11%, y síntomas graves en el 1%. Los síntomas más prevalentes fueron fatiga (67%), insomnio (44%), ansiedad (42%), mialgia (41%) y anosmia (41%). La prevalencia se redujo a la mitad en los primeros 5 cinco meses, pero en muchos casos se prolongó durante más de un año. En el análisis multivariado los síntomas tendieron a agruparse en clusters (cognitivos, neuropsiquiátricos, cardiorrespiratorios, digestivos, otros). La necesidad de cambiar de área de trabajo fue del 16% y la falta de reincorporación al trabajo del 7%, relacionadas con la mayor edad, el número de síntomas y la gravedad del curso inicial. Conclusión: En muchos casos la persistencia de los síntomas post-COVID puede ser prolongada y tener un impacto laboral en los profesionales sanitarios, requiriendo la adopción de políticas específicas para reducir el daño.

Circulating microRNAs as biomarkers of Chagas cardiomyopathy.

Background: Chagas cardiomyopathy (CHCM) is the most important clinical manifestation of Chagas disease. The analysis of cardiac miRNAs may contribute to predicting the progression to CHCM in Chagas indeterminate phase and/or to the differential diagnosis for cardiomyopathy. Methods: We carried out a case-control study to identify circulating miRNAs associated with CHCM. We assigned 104 participants to four groups: healthy controls (HC), Chagas non-cardiomyopathy controls, CHCM cases, and ischemic cardiomyopathy controls. We performed a clinical, echocardiographic, and laboratory evaluation and profiled circulating miRNA in the serum samples. Results: Differences between groups were observed in clinical variables and in the analysis of miRNAs. Compared to HC, CHCM participants had 4 over-expressed and 6 under-expressed miRNAs; miR-95-3p and miR-130b-3p were upregulated in CHCM compared with controls, Chagas non-cardiomyopathy and ischemic cardiomyopathy participants, suggesting that might be a hallmark of CHCM. Analysis of gene targets associated with cardiac injury yielded results of genes involved in arrhythmia generation, cardiomegaly, and hypertrophy. Conclusions: Our data suggest that the expression of circulating miRNAs identified by deep sequencing in CHCM could be associated with different cardiac phenotypes in CHCM subjects, compared with Chagas non-CHCM, ischemic cardiomyopathy controls, and healthy controls.

Sex Differences in the Clinical Presentation of Acute Coronary Syndromes.

The clinical presentation of acute coronary syndromes (ACS) as ST-elevation ACS (STEACS) or non-ST-elevation ACS (NSTEACS) differs between women and men. The aim of this study was to describe the difference in the clinical presentation of ACS between sexes. A total of 10,019 patients included in the Epi-Cardio Registry were analyzed. A higher proportion of women than men presented with NSTEACS (60.3% vs 46.7%; P <0.001). The difference between sexes was driven by a higher prevalence of ACS with non-obstructive coronary arteries (20.9% vs 6.6%) mainly in young women, since ACS without coronary lesions were mostly NSTEACS (77.7% vs 22.3%). In patients with obstructive coronary heart disease, there were no differences in the clinical presentation between sexes. In conclusion, younger women are more likely than men to present ACS with non-obstructive coronary arteries, whereas no significant difference exists between sexes regarding the prevalence of ACS with obstructive coronary artery disease.

Intramyocardial Dissecting Hematoma: A Mechanical Complication Needing Surgical Therapy?

Intramyocardial dissecting hematoma is a form of cardiac rupture caused by myocardial infarction, percutaneous coronary intervention, or trauma. It is a cavity between myocardial fibers caused by partial rupture of the ventricular wall. Therapeutic management, including the timing for surgical approach, has not been standardized. We present a case series describing 4 patients. (Level of Difficulty: Intermediate.).

High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial.

BACKGROUND: The role of oral vitamin D3 supplementation for hospitalized patients with COVID-19 remains to be determined. The study was aimed to evaluate whether vitamin D3 supplementation could prevent respiratory worsening among hospitalized patients with COVID-19. METHODS AND FINDINGS: We designed a multicentre, randomized, double-blind, sequential, placebo-controlled clinical trial. The study was conducted in 17 second and third level hospitals, located in four provinces of Argentina, from 14 August 2020 to 22 June 2021. We enrolled 218 adult patients, hospitalized in general wards with SARS-CoV-2 confirmed infection, mild-to-moderate COVID-19 and risk factors for disease progression. Participants were randomized to a single oral dose of 500 000 IU of vitamin D3 or matching placebo. Randomization ratio was 1:1, with permuted blocks and stratified for study site, diabetes and age (≤60 vs >60 years). The primary outcome was the change in the respiratory Sepsis related Organ Failure Assessment score between baseline and the highest value recorded up to day 7. Secondary outcomes included the length of hospital stay; intensive care unit admission; and in-hospital mortality. Overall, 115 participants were assigned to vitamin D3 and 105 to placebo (mean [SD] age, 59.1 [10.7] years; 103 [47.2%] women). There were no significant differences in the primary outcome between groups (median [IQR] 0.0 [0.0-1.0] vs 0.0 [0.0-1.0], for vitamin D3 and placebo, respectively; p = 0.925). Median [IQR] length of hospital stay was not significantly different between vitamin D3 group (6.0 [4.0-9.0] days) and placebo group (6.0 [4.0-10.0] days; p = 0.632). There were no significant differences for intensive care unit admissions (7.8% vs 10.7%; RR 0.73; 95% CI 0.32 to 1.70; p = 0.622), or in-hospital mortality (4.3% vs 1.9%; RR 2.24; 95% CI 0.44 to 11.29; p = 0.451). There were no significant differences in serious adverse events (vitamin D3 = 14.8%, placebo = 11.7%). CONCLUSIONS: Among hospitalized patients with mild-to-moderate COVID-19 and risk factors, a single high oral dose of vitamin D3 as compared with placebo, did not prevent the respiratory worsening. TRIAL REGISTRATION: ClincicalTrials.gov Identifier: NCT04411446.

Applying systems thinking to identify enablers and challenges to scale-up interventions for hypertension and diabetes in low-income and middle-income countries: protocol for a longitudinal mixed-methods study.

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and diabetes outcomes. A systematic inquiry of these projects will provide necessary scientific insights into the enablers and challenges in the scale up of complex NCD interventions. METHODS AND ANALYSIS: We will apply systems thinking (a holistic approach to analyse the inter-relationship between constituent parts of scaleup interventions and the context in which the interventions are implemented) and adopt a longitudinal mixed-methods study design to explore the planning and early implementation phases of scale up projects. Data will be gathered at three time periods, namely, at planning (TP), initiation of implementation (T0) and 1-year postinitiation (T1). We will extract project-related data from secondary documents at TP and conduct multistakeholder qualitative interviews to gather data at T0 and T1. We will undertake descriptive statistical analysis of TP data and analyse T0 and T1 data using inductive thematic coding. The data extraction tool and interview guides were developed based on a literature review of scale-up frameworks. ETHICS AND DISSEMINATION: The current protocol was approved by the Monash University Human Research Ethics Committee (HREC number 23482). Informed consent will be obtained from all participants. The study findings will be disseminated through peer-reviewed publications and more broadly through the GACD network.

High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial (CARED-TRIAL).

OBJECTIVES: To evaluate whether a single high dose of oral cholecalciferol improves the respiratory outcomes as compared with placebo among adults COVID-19 patients at moderate risk of clinical complications. TRIAL DESIGN: The CARED trial is an investigator-initiated, multicentre, randomized, parallel, two-arm, sequential, double-blind and placebo-controlled clinical trial. It was planned as a pragmatic trial since the inclusion criteria are broad and the study procedures are as simple as possible, in order to be implemented in the routine clinical practice in general wards in the pandemic setting and a middle-income country context. The sequential design involves two stages. The first stage will assess the effects of vitamin D supplementation on blood oxygenation (physiological effects). The second stage will assess the effects on clinical outcomes. PARTICIPANTS: Participants of either gender admitted to general adult wards in 21 hospital sites located in four provinces of Argentina are invited to participate in the study if they meet the following inclusion criteria and none of the exclusion criteria: Inclusion criteria SARS-CoV-2 confirmed infection by RT-PCR; Hospital admission at least 24 hours before; Expected hospitalization in the same site ≥24 hours; Oxygen saturation ≥90% (measured by pulse oximetry) breathing ambient air; Age ≥45 years or at least one of the following conditions: ○ Hypertension; ○ Diabetes; ○ At least moderate COPD or asthma; ○ Cardiovascular disease (history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or valve replacement surgery); ○ Body mass index ≥30; Willingness to sign informed consent (online supplementary material 1 and 2). EXCLUSION CRITERIA: Age <18 years; Women in childbearing age; >= 72 hs since current admission; Requirement for a high dose of oxygen (>5 litres/minute) or mechanical ventilation (non-invasive or invasive); History of chronic kidney disease requiring haemodialysis or chronic liver failure; Inability for oral intake. Chronic supplementation with pharmacological vitamin D; Current treatment with anticonvulsants; History of: ○ Sarcoidosis; ○ Malabsorption syndrome; ○ Known hypercalcemia or serum calcium >10.5 mg/dL; Life expectancy <6 months; Known allergy to study medication; Any condition at discretion of investigator impeding to understand the study and give informed consent. INTERVENTION AND COMPARATOR: The intervention consists in a single oral dose of 500.000 IU of commercially available cholecalciferol soft gel capsules (5 capsules of 100.000 IU) or matching placebo MAIN OUTCOMES: The primary outcome for the first stage is the change in the respiratory Sepsis-related Organ Failure Assessment (SOFAr) score between pre-treatment value and the worst value recorded during the first 7 seven days of hospitalization, the death or discharge, whichever occurs first. The SOFAr score measured as the ratio between the pulse oximetry saturation (SpO2) and FiO2 (27, 28) is used instead of the arterial partial pressure of oxygen (PaO2). SOFAr score is a 4-points scale, with higher values indicating deeper respiratory derangement as follows: 1 PaO2 <400; 2 PaO2 <300; 3 PaO2 <200; 4 PaO2 <100. The primary outcome for the second stage is the combined occurrence of requirement ≥40% of FiO2, invasive or non-invasive ventilation, up to 30 days or hospital discharge. RANDOMISATION: A computer-generated random sequence and the treatment assignment is performed through the web-based randomization module available in the electronic data capture system (Castor®). A randomization ratio 1:1, stratified and with permuted blocks was used. Stratification variables were diabetes (yes/no), age (≤60/>60 years) and the site. BLINDING (MASKING): Double-blind was achieved by using placebo soft gel capsules with the same organoleptic properties as the active medication. Central management of the medication is carried out by a pharmacist in charge of packaging the study drug in unblinded fashion, who have no contact with on-site investigators. Medication is packaged in opaque white bottles, each containing five soft gel capsules of the active drug or matching placebo, corresponding to complete individual treatment. Treatment codes are kept under the pharmacist responsibility, and all researchers are unaware of them. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The first stage is planned to include 200 patients (100 per group), the second stage is planned to include 1064 additional patients. The total sample size is 1264 patients. TRIAL STATUS: Currently the protocol version is the number 1.4 (from October 13th, 2020). The recruitment is ongoing since August 11th, 2020, and the first subject was enrolled on August 14th. Since then, 21 sites located in four provinces of Argentina were initiated, and 167 patients were recruited by January 11th, 2021. We anticipate to finish the recruitment for the first stage in mid-February, 2021, and in August, 2021 for the second stage. TRIAL REGISTRATION: The study protocol is registered in ClinicalTrials.gov (identifier number NCT04411446 ) on June 2, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Association Between Vitamin D Deficiency and COVID-19 Incidence, Complications, and Mortality in 46 Countries: An Ecological Study.

Each patient's immune defenses play a major role in mitigating the impact (ie, morbidity and mortality) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Vitamin D is an important modulator of the immune system. Although serum 25-hydroxyvitamin D levels can be raised through diet or supplements, most vitamin D in the body is the result of dermal synthesis from ultraviolet radiation. The production of vitamin D in the skin, however, can be limited by latitude, skin-covering clothes, the use of sunblock, and skin pigmentation. Vitamin D deficiency affects a high percentage of the world population. Serum 25-hydroxyvitamin D levels are suboptimal, not only in specific risk groups but also in adults from many countries. Low vitamin D levels, therefore, represent a risk factor for several different pathologies, including SAR-CoV-2. This study used an ecological design to assess the association between vitamin D deficiency and COVID-19 incidence, complications, and mortality across 46 countries. All data were obtained from published sources. The results of the study suggest an association at the population level between the prevalence of vitamin D deficiency and the risk of being infected with COVID-19, severity of the disease, and risk of dying from it.

[Concerns and demands regarding COVID-19. Survey of health personnel]. / Preocupaciones y demandas frente a COVID-19. Encuesta al personal de salud.

The COVID-19 pandemic affected the organization of health services and had consequences for health teams, according to the pre-existing safety and working conditions. During the first week of April 2020, a cross sectional study was carried out with a qualitative-quantitative approach. The aim was to explore the conditions determining the organizational climate: leadership, communication, institutional resources, cohesion/conflict management, and training; and how these were perceived by health personnel to deal with the pandemic. A total of 5670 healthcare workers participated in an online survey and 50 were interviewed, from all subsectors of the Argentinean health system (public, private and union-health insurance); 72.9% were women, 51.4% were physicians, and the predominant age group was under 40 years. In the qualitative sample (interviews), 52% were men, 62% were physicians, and the average age was 44.8 years. The dimensions of the organizational climate were stratified and five independent predictors of perception of conditions were identified: age, gender, tasks performed, health system subsector, and jurisdiction. The condition most frequently perceived as inadequate were the inaccessibility of institutional resources and the access to personal protective equipment was a major concern. Claims included the need of institutional strategies to support healthcare workers and of a clear and uniform communication. In conclusion, at the time of the study, the health personnel perceived serious deficits in their organizations regarding the conditions necessary to confront COVID-19, with differences among subsectors of the health system.

La pandemia por COVID-19 afectó la organización de los servicios de salud y tuvo consecuencias en los equipos de salud, según las condiciones laborales y de bioseguridad pre-existentes en cada institución. Durante la primera semana de abril de 2020 se realizó un estudio de corte transversal. El objetivo fue indagar acerca de las condiciones que determinan el clima organizacional: liderazgo, comunicación, recursos institucionales, cohesión/gestión de conflictos y capacitación; y cómo éstas eran percibidas por el personal de salud para hacer frente a la pandemia. Se realizaron 5670 encuestas a trabajadores/as y 50 entrevistas a informantes clave de los tres subsectores del sistema de salud (público, privado y de seguridad social). En las encuestas, el 72.9% fueron mujeres, el 51.4% médicos/as y el grupo etario predominante fue el de menores de 40 años. El 47.8% de los/as participantes refirió pluriempleo. En las entrevistas, el 52% fueron varones, el 60% médicos/ as, la edad media 44.8 años. Se estratificaron las dimensiones y se identificaron predictores independientes de percepción: edad, género, tipo de tareas, subsector y jurisdicción. La dimensión percibida con mayor frecuencia como inadecuada fue la de recursos institucionales y la disponibilidad de equipos de protección personal fue identificada como una de las principales preocupaciones. Surgieron demandas de estrategias de contención para el personal de salud y de comunicación institucional clara y uniforme. En conclusión, al momento del estudio el personal de salud percibía serios déficits en sus organizaciones respecto de las condiciones necesarias para enfrentar la pandemia, con diferencias entre subsectores del sistema.

Multicap to improve adherence after acute coronary syndromes: results of a randomized controlled clinical trial.

BACKGROUND: Adherence to treatment after a myocardial infarction (MI) is poor, even in the early postinfarction period. Combining evidence-based drugs into a multicap could improve adherence in this population. No previous randomized trial assessing fixed-dose combination therapy has included patients early after a MI. We aimed to assess if a multicap containing four secondary prevention drugs increases adherence to treatment at 6 months after MI hospitalization. The study was designed as a randomized, parallel, open-label, controlled trial. METHODS: Patients were randomized within 7 days of a MI to either multicap or control group. The multicap group received a capsule containing aspirin, atenolol, ramipril, and simvastatin. The control group received each drug in separate pills. The primary outcome was adherence at 6 months. We also measured blood pressure, heart rate, serum cholesterol levels, C-reactive protein, and platelet aggregation. RESULTS: The study was stopped prematurely when 100 patients were included for futility. At 6 months, 92 (95.8%) patients were adherent to medical treatment: 98.0% in the multicap group and 93.5% in the control group [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.14; p = 0.347]. There were no differences between groups in systolic blood pressure (p = 0.662), diastolic blood pressure (p = 0.784), heart rate (p = 0.533), total cholesterol (p = 0.760), LDL-c (p = 0.979), C-reactive protein (p = 0.399), or in the proportion of patients with adequate platelet aggregation inhibition (p = 0.600). CONCLUSIONS: The study did not find any improvement in the adherence at 6 months after a MI with a multicap-based strategy (Multicap for Increase Adherence After Acute Myocardial Infarction; [ ClinicalTrials.gov identifier: NCT02271178]).

Análisis del síndrome post-COVID-19 en personal de salud: comparación sobre condiciones de género y trabajo / Analysis of long COVID in health personnel: comparing gender and work factors

Resumen Introducción : El objetivo del estudio fue describir la prevalencia del reporte de síndrome post-COVID-19 y sus características según género, profesión y otros de terminantes sociales, en personal de salud. Métodos : Se realizó un estudio de corte transver sal en profesionales de salud con antecedentes de COVID-19 en América Latina, y para este análisis se seleccionaron las 2030 respuestas de Argentina. Se recolectaron datos sociodemográficos, información sobre el curso inicial de la enfermedad COVID-19, y persistencia de 21 síntomas más allá del primer mes, su gravedad, evolución clínica y requerimiento de ser vicios de salud. Resultados : Se identificó que la prevalencia re portada de síndrome post-COVID-19 fue mayor en mujeres para cada uno de los grupos de síntomas explorados. La gravedad del cuadro inicial, el género femenino, la profesión de enfermería, el multiempleo y trabajar en áreas de emergencia fueron variables independientes. Discusión : La mayor sobrecarga del personal de sa lud durante la pandemia -altamente feminizado- y las determinaciones de género asociadas podrían explicar parcialmente estos hallazgos.

Abstract Introduction : This study aimed to describe the re ported prevalence of post-COVID-19 syndrome and its characteristics by gender, profession, and other deter minants among health care workers. Methods : A cross-sectional study was conducted among health workers with a history of COVID-19 in Latin America, and the 2030 responses from Argentina were selected for this analysis. Sociodemographic infor mation, as well as data on initial course of COVID-19, and the persistence of 21 symptoms beyond the first month, their severity, clinical evolution, and health care demands were collected. Results : The reported prevalence of post-COVID-19 syndrome was higher in women for each of the symptom clusters studied. Severity of the initial symptoms, female gender, nursing profession, multi-employment, and work ing in emergency areas were all independent variables. Discussion : The greater strain of health care workers during the pandemic -highly feminized- and the as sociated gender conditions may partially explain these findings.

Síndrome post COVID-19. Gravedad y evolución en 4673 trabajadores sanitarios / Post COVID-19 syndrome. Severity and evolution in 4673 health care workers

Resumen Introducción : La evolución del síndrome post COVID ha sido variable y carecemos de información sobre su impacto en los profesionales de la salud. Métodos : Realizamos una encuesta a través de una red social en profesionales de la salud sobre casos de síndrome post COVID-19 confirmados con PCR. En un cuestionario web, preguntamos sobre 21 síntomas, su gravedad, duración, grado de afectación de la actividad y reincorporación al trabajo. Resultados : Respondieron 4673 profesionales sanita rios de 21 países, edad media de 47 años, 64% mujeres. El curso inicial fue asintomático en el 9%, síntomas leves en el 36%, síntomas moderados sin hospitalización en el 40% o con hospitalización en el 11%, y síntomas graves en el 1%. Los síntomas más prevalentes fueron fatiga (67%), insomnio (44%), ansiedad (42%), mialgia (41%) y anosmia (41%). La prevalencia se redujo a la mitad en los primeros 5 cinco meses, pero en muchos casos se prolongó durante más de un año. En el análisis multi variado los síntomas tendieron a agruparse en clusters (cognitivos, neuropsiquiátricos, cardiorrespiratorios, digestivos, otros). La necesidad de cambiar de área de trabajo fue del 16% y la falta de reincorporación al tra bajo del 7%, relacionadas con la mayor edad, el número de síntomas y la gravedad del curso inicial. Conclusión : En muchos casos la persistencia de los síntomas post COVID-19 puede ser prolongada y te ner un impacto laboral en los profesionales sanitarios, requiriendo la adopción de políticas específicas para reducir el daño.

Abstract Background : The evolution of post COVID-19 syn drome has been variable and we lack information on its impact on healthcare professionals. Methods : We conducted a survey through a social network in health professionals on post COVID-19 syn drome cases confirmed with PCR. In a web-based ques tionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work. Results : 4673 health professionals from 21 countries responded, mean age of 47 years, 64% women. The initial course was asymptomatic in 9%, mild symptoms 36%, moderate symptoms without hospitalization 40% or with hospitalization 11%, and severe symptoms 1%. The most prevalent symptoms were fatigue (67%), insomnia (44%), anxiety (42%), myalgia (41%) and anosmia (41%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the mul 670 tivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7%, related to older age, number of symptoms and severity of the initial course. Conclusion : in many cases the persistence of post- COVID symptoms can be prolonged and have an occu pational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.

Valor pronóstico del ecocardiograma con strain bidimensional por Speckle Tracking en pacientes con amiloidosis asociada a transtiretina / Prognosis value of the echocardiogram with bidimensional strain by speckle tracking in patients with amyloidosis associated with transthyretin

[RESUMEN]: La amiloidosis cardíaca asociada a transtiretina (ATTR) es una cardiomiopatía infiltrativa caracterizada por el depósito de fibrillas en el miocardio, asociada a un mal pronóstico, incluye dos subtipos: hereditaria (ATTRh) y natural. La mutación Val30Met es la más frecuente a nivel mundial. El diagnóstico es desafiante, se basa en un alto grado de sospecha clínica, una combinación de técnicas de imagen y en algunos casos una biopsia endomiocárdica. Las nuevas técnicas ecocardiográficas han aportado avances en el diagnóstico gracias a su mejor sensibilidad en comparación con parámetros clásicos. OBJETIVO: Evaluar si el deterioro del strain (deformación) longitudinal global (SLG) del ventrículo izquierdo (VI) evaluada por ecocardiografía en pacientes con ATTRh Val30Met, se asocia a eventos cardiovasculares adversos. METODOLOGÍA: Estudio prospectivo de Cohorte. Se evaluaron en total 53 pacientes con amiloidosis tratados en el Hospital "El Cruce" de Florencio Varela desde junio de 2014 y se incluyeron 26 pacientes con la mutación Val30Met, entre marzo y noviembre del 2019 que cumplían con los criterios de inclusión. RESULTADOS: Se observaron eventos (requerimiento de marcapaso, desarrollo de insuficiencia cardíaca y muerte) en el 53.8 % de los pacientes, de los cuales 71,4 % eran hombres (OR: 0,30 (IC95: 0,05-1,54), p=0.13). De los 5 pacientes con amiloidosis de inicio tardío (>60 años) el 100 % presentó eventos (p 0,03). En el análisis univariado, las variables que mostraron asociación con eventos fueron: edad de inicio de los síntomas (p= <0.001), edad de diagnóstico (p=0.004), inicio temprano (p= 0.02), bajo peso (p= 0.004), disnea (p= <0.001), presencia de HVI (p=0.005), disfunción diastólica (p=0.007), dilatación de la AI (p=0.003) y el SLG promedio (p= 0.003). CONCLUSIONES: La FEY (fracción de eyección) del VI se mantiene normal hasta etapas avanzadas, por lo que se considera inadecuada para la correcta valoración de estos pacientes siendo necesarios métodos alternativos que aumenten la sensibilidad en el período preclínico. El punto de corte de SLG-14.4 ± 4.5% discriminó la evolución a eventos cardiovasculares adversos.

[ABSTRACT]: Transthyretin-associated cardiac amyloidosis (ATTR) is an infi ltrative cardiomyopathy characterized by the deposition of fi brils in the myocardium, associated with a poor prognosis, it includes two subtypes: hereditary (hATTR) and natural. The Val30Met mutation is the most frequent worldwide. The diagnosis is challenging, based on a high degree of clinical suspicion, a combination of imaging techniques, and in some cases an endomyocardial biopsy. The new echocardiographic techniques have brought advances in diagnosis thanks to their better sensitivity compared to classical parameters. OBJECTIVE: To assess whether the deterioration of the global longitudinal strain (deformation) of the left ventricle (LV) evaluated by echocardiography in patients with hATTR Val30Met is associated with adverse cardiovascular events. METHODS: Prospective cohort study. A total of 53 patients with amyloidosis treated at the Hospital "El Cruce" in Florencio Varela since June 2014 were evaluated, 26 patients with the Val30Met mutation were included, between March and November 2019, who met the inclusion criteria. RESULTS: Of the 5 patients with late-onset amyloidosis (> 60 years), 100% had events (p 0.03). Events (requirement for a pacemaker, development of heart failure and death) were observed in 53.8% of the patients, of which 71.4% were men (OR: 0.30 (CI95: 0.05-1.54), p = 0.13). In the univariate analysis, the variables that showed an association with events were: age of onset of symptoms (p = <0.001), age of diagnosis (p = 0.004), early onset (p = 0.02), underweight (p = 0.004), dyspnea (p = <0.001), presence of LVH (p = 0.005), diastolic dysfunction (p = 0.007), LA dilation (p = 0.003) and mean GLS (p = 0.003). CONCLUSIONS: The LV EF (ejection fraction) remains normal until advanced stages, which is why it is considered inadequate for the correct evaluation of these patients, and alternative methods are necessary to increase sensitivity in the preclinical period. The cut-off point of GLS-14.4 ± 4.5% discriminated the evolution to adverse cardiovascular events.

Resistencia a la heparina en pacientes con síndrome respiratorio agudo grave coronavirus tipo 2: a propósito de un caso / Heparin resistance in patients with severe acute respiratory syndrome coronavirus type 2: a case report

[RESUMEN]: Los pacientes con Covid 19 causado por el virus del síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2) desarrollan coagulopatía sobre todo en los casos graves, lo que conlleva un alto riesgo de presentar eventos trombóticos. En estos pacientes, el uso de terapia anticoagulante con heparina no fraccionada (HNF) resulta en ocasiones de difícil manejo. Como sabemos, su utilización debe controlarse mediante el tiempo de tromboplastina parcial activada (APTT), con un valor referencial de 1.5 a 2.5 del valor basal. Debido a la respuesta inflamatoria severa provocada por SARS-CoV-2 hay un aumento en la síntesis de fibrinógeno y/o Factor VIII (FVIII), que puede producir la ausencia de prolongación del APTT a pesar de dosis altas de HNF, fenómeno conocido como resistencia bioquímica a la heparina. Además, en pacientes con Covid 19 se ha descrito disminución de los valores de antitrombina (AT), aunque dentro del rango hemostático, respecto a un grupo control. Se describirá el caso de un paciente internado en nuestra institución, con diagnóstico de Covid 19 grave y resistencia bioquímica a la heparina, lo que resultó en un difícil manejo de la anticoagulación.

[ABSTRACT]: Patients with Covid 19, caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) can develop a coagulopathic state, mostly in severe cases, with a high risk of thrombotic complications. In these patients, the use of anticoagulant therapy with unfractioned heparin (UFH) can be challenging. UFH must be controlled by the activated partial thromboplastin time (aPTT), with a referetial value of 1.5 ­ 2.0 times the baseline value. SARS-CoV-2 produces a severe infl ammatory response which causes an elevation in fi brinogen and Factor VIII (FVIII) liver synthesis. This can interfere with the aPTT, not being able to raise it to therapeutically desired ranges in spite of high doses of UFH, a phenomenon known as heparin laboratory resistance. In Covid 19 patients, a lower level of antithrombin (AT) synthesis with respect to a control group has also been described, although witihn the hemostatic range. We will describe a case report from our hospital, with a diagnosis of severe Covid 19 and heparin laboratory resistance, which led to diffi culties in the anticoagulation therapy management.

Condiciones y medio ambiente de trabajo en salud: modelo conceptual para áreas remotas y rurales

Se propone un modelo conceptual sobre condiciones y medio ambiente de trabajo en salud que integra la evidencia disponible para facilitar el diseño y la evaluación de intervenciones orientadas a mejorar la atracción, captación y retención del personal de salud en el primer nivel de atención de áreas rurales y remotas. Se consultó la evidencia teórica, empírica y testimonial para fundamentar la propuesta y se sintetizaron 15 modelos difundidos en los últimos 20 años. El artículo da cuenta de la diversidad de perspectivas y la complejidad que conlleva establecer las dimensiones que deben considerarse en una propuesta que sea útil para aplicar a las políticas de recursos humanos en salud. El modelo propuesto incluye cuatro categorías de componentes: factores del contexto externo, factores organizacionales, condiciones del empleo y del trabajo, y factores individuales. Los límites entre los componentes –así como el peso y la influencia de cada uno– varían en función de la relación entre ellos y de la interacción con el medio, por lo que su interpretación debe adecuarse al ámbito en que se pretenda aplicar. A partir de este modelo conceptual, el diseño y la evaluación de las intervenciones dirigidas a incrementar la disponibilidad de personal de salud –en particular en el primer nivel de atención de áreas rurales y remotas de la Región de las Américas– deberían surgir de una interacción entre las políticas de salud y empleo, y las realidades y expectativas de los trabajadores y las comunidades.

This report proposes a conceptual model on workplace environment and working conditions that integrates the available evidence to facilitate the design and evaluation of interventions aimed at improving the attraction, recruitment and retention of health personnel at the first level of care in rural and remote areas. Theoretical, empirical and testimonial evidence was consulted to support the model, and 15 frameworks disseminated in the last 20 years were synthesized. The article shows the diversity of perspectives and the complexity involved in establishing the dimensions to be considered in a proposal that is useful to apply to human resources for health policies. The proposed model includes four categories of components: factors of the external context, organizational factors, employment and work conditions, and individual factors. The boundaries between the components – as well as the weight and influence of each one– vary according to the interrelationship among them and the interaction with the environment, and thus its interpretation must be adapted to the context in which it is intended to be applied. Based on this conceptual model, the design and evaluation of interventions aimed at increasing the availability of health personnel –particularly at the primary care level in rural and remote areas of the Region of the Americas– should emerge from an interaction between health and employment policies, and the realities and expectations of workers and the communities.