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This paper presents the results of the modelling and analysis of the reading process within the Italian publishing house Einaudi after the Second World War, with a special focus on Natalia Ginzburg (1916-1991). More specifically, the corpus of sources consists of the reading reports concerning contemporary narrative works, which represent a fundamental step in the decision-making process that leads to the publication of a work and therefore to the construction of the catalogue of a publishing house. The examination of Natalia Ginzburg’s reading reports, mostly unpublished, provides the basis for a critical reflection on her editorial activity, a reflection which is rooted in the belief that editorial writing represents a complex critical genre that deserves to be investigated by specific methods. The tools (in the present case UML, PostgreSQL, XML TEI) and methods of the Digital Humanities have made a major contribution to the realisation of the scientific objectives of the research work. On the one hand, they have made it possible to model, represent and interrogate the corpus of documents in a relevant and efficient way; on the other hand, they were fundamental and indispensable from a methodological, heuristic and interpretative point of view.

Introduction Scaling up interventions targeting non-communicable diseases (NCDs) is a global health priority, and implementation research can contribute to that effort. In 2019, the Global Alliance for Chronic Diseases funded 27 implementation research studies to improve evidence for scaling up interventions targeting prevention and/or control of hypertension and/or diabetes in low-resource settings. We examined these studies to improve the understanding of the implementation factors, including challenges and facilitators, that influence the early implementation phase of scale-up research projects targeting NCDs.Methods This qualitative study was undertaken between August 2020 and July 2021. 43 semi-structured interviews were conducted with project investigators, implementers and policymakers, across 19 diverse scale-up projects, being implemented in 20 countries. The transcripts were inductively, open-coded using thematic analysis. Generated themes were mapped systematically to four out of five domain categorisations of the Consolidated Framework for Implementation Research (CFIR); the innovation domain fell outside the scope of this study.Results Highlighted findings using CFIR are: (i) outer setting: influence of politics, lack of coordination between government departments and differing agendas towards NCDs hindered implementation while reliable and trustworthy government connections proved useful; (ii) inner setting: commitment of resources for implementation was a challenge while research capacity, work culture and trustworthy networks facilitated implementation; (iii) individuals: high-level stakeholder support and leadership was essential; (iv) process: extensive time and efforts required for stakeholder engagement towards local contextualisation was challenging, while collaborating, joint reflection, effective communication and adaptation facilitated. COVID-19 provided both challenges and opportunities and these varied depending on the intervention characteristics and study objectives.Conclusion Researchers supporting the scale-up of complex interventions targeting NCDs need to leverage on existing trusting relationships and foster equitable stakeholder partnerships through research. Interpersonal skills and good communication are essential complements to research expertise and must be considered during capacity building.

BackgroundChagas 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.MethodsWe 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.ResultsDifferences 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.ConclusionsOur 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.

Aim: To evaluate angiotensin II (Ang II) and Ang-(1-7) levels and the cytokine profile in patients hospitalized with mild coronavirus disease 2019 (COVID-19) and contrast them with patients with identical clinical conditions but treated with high doses of vitamin D (vitD). Methods: From the 218 patients recruited (ClinicalTrials.gov NCT04411446), 16 participated in this sub-study and were randomized to a single oral dose of 500,000 IU vitD (n = 10) or placebo (n = 6). Plasmatic Ang II and Ang-(1-7) levels were determined by radioimmunoassay and interleukins (ILs) 1, 6, 8, and 10 and tumor necrosis factor alpha (TNF-α) by enzyme-linked immunosorbent assay before and after treatment. Parallel, serum 25-hydroxyvitamin D3 (25-OH vitD) concentrations as vitD status was measured by a chemiluminescence immunoassay. Results: A trend towards an increase in Ang-(1-7) and a decrease in Ang II levels were observed in placebo- and vitD-treated COVID-19 patients compared to baseline values. There was no difference in Ang II and Ang-(1-7) levels between placebo- and vitD-treated COVID-19 patients. Similar results were obtained with ILs profile. COVID-19 patients showed an increase in the protective component of the RAS which was not improved by vitD treatment. Conclusions: VitD did not improve RAS disbalance in COVID-19. Notwithstanding, the authors visualize that acute treatment with high doses of vitD may show a trend to a decline in inflammatory ILs and an increase in protective markers. Finally, the authors would like to highlight the limitations of this preliminary study, namely the small number of patients and the use of a large single bolus dose of vitD rather than lower daily doses for extended periods with prolonged follow-up times. All these factors need special consideration in the designs of new vitD supplementation trials. All these factors need special consideration in the designs of new vitD supplementation trials (ClinicalTrials.gov identifier: NCT04411446).

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.

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.

Objetivo. Identificar y sistematizar la evidencia empírica disponible sobre 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. Métodos. Revisión rápida de revisiones, seleccionadas según criterios de pertinencia, elegibilidad e inclusión con búsquedas en bases de datos electrónicas, de literatura gris y manual. Se empleó el AMSTAR I para evaluar la calidad de revisiones sistemáticas y un análisis temático para síntesis de resultados. Resultados. Se incluyeron 16 revisiones, una de las cuales contenía a su vez 14 revisiones. Del total, 20 revisiones analizaron factores y 9 evaluaron efectividad de intervenciones. La evidencia sobre factores es abundante, pero de limitada calidad. Los factores individuales, familiares y la “exposición rural previa” se asociaron a mayor captación; factores organizacionales y del contexto externo fueron gravitantes en la retención. El trabajo en red y el apoyo profesional incidieron en la captación y retención. La evidencia sobre efectividad de intervenciones fue limitada, en cantidad y calidad. El tipo de intervención más frecuentemente empleada fueron los incentivos. Conclusiones. La evidencia sobre factores que se relacionan positivamente con la captación y retención de trabajadores en el primer nivel de atención de áreas rurales, remotas o desatendidas es suficiente y debería ser tenida en cuenta al diseñar intervenciones. La evidencia de calidad sobre la efectividad de intervenciones es escasa. Se requieren más estudios controlados con rigurosidad metodológica, particularmente en las Américas.

BackgroundThe 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 findingsWe 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%).ConclusionsAmong 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 registrationClincicalTrials.gov Identifier: NCT04411446.

Abstract 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 = 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 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).

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]).

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.