The ANGPTL3-4-8 Axis in Normal Gestation and in Gestational Diabetes, and Its Potential Involvement in Fetal Growth.

Dyslipidemia in gestational diabetes has been associated with worse perinatal outcomes. The ANGPTL3-4-8 axis regulates lipid metabolism, especially in the transition from fasting to feeding. In this study, we evaluated the response of ANGPTL3, 4, and 8 after the intake of a mixed meal in women with normal glucose tolerance and gestational diabetes, and we assessed their gene expressions in different placental locations. Regarding the circulating levels of ANGPTL3, 4, and 8, we observed an absence of ANGPTL4 response after the intake of the meal in the GDM group compared to its presence in the control group. At the placental level, we observed a glucose tolerance-dependent expression pattern of ANGPTL3 between the two placental sides. When we compared the GDM pregnancies with the control pregnancies, a downregulation of the maternal side ANGPTL3 expression was observed. This suggests a dysregulation of the ANGPTL3-4-8 axis in GDM, both at the circulating level after ingestion and at the level of placental expression. Furthermore, we discerned that the expressions of ANGPTL3, 4, and 8 were related to birth weight and placental weight in the GDM group, but not in the control group, which suggests that they may play a role in regulating the transplacental passage of nutrients.

Pregnancy homocysteine and cobalamin status predict childhood metabolic health in the offspring.

BACKGROUND: Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce. METHODS: Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads. RESULTS: Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys. CONCLUSIONS: Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight. IMPACT: Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights.

BACKGROUND: The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE). METHODS: A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015-2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs. RESULTS: Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between - 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%. CONCLUSIONS: The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE.

DNA Methylation in Gestational Diabetes and its Predictive Value for Postpartum Glucose Disturbances.

CONTEXT: DNA methylation in the diagnosis of gestational diabetes. OBJECTIVE: To assess the value of DNA methylation in the diagnosis of gestational diabetes (GDM) and in the prediction of maternal postpartum glucose disturbances. METHODS: Two-stage observational study performed between July 2006 and December 2010, at University Hospital. Forty-eight randomly selected pregnant women formed the discovery cohort (24 with GDM and 24 controls) and 252 pregnant women (94 with GDM and 158 controls) formed the replication cohort. GDM women were re-evaluated 4 years postpartum. The main outcome measures were GDM, type 2 diabetes or prediabetes at 4 years postpartum. RESULTS: We identified 3 CpG sites related to LINC00917, TRAPPC9, and LEF1 that were differentially methylated in women with GDM and abnormal glucose tolerance; and sites associated with LINC00917 and TRAPPC9 were independently associated with an abnormal glucose tolerance status 4 years postpartum after controlling for clinical variables. Moreover, the site associated with LINC00917 and the combination of the 3 sites had the highest predictive values. CONCLUSION: Our results suggest that some of these sites may be implicated in the development of GDM and postpartum abnormal glucose tolerance.

Cord Blood Advanced Lipoprotein Testing Reveals an Interaction between Gestational Diabetes and Birth-Weight and Suggests a New Early Biomarker of Infant Obesity.

Abnormal lipid metabolism is associated with gestational diabetes mellitus (GDM) and is observed in neonates with abnormal fetal growth. However, the underlying specific changes in the lipoprotein profile remain poorly understood. Thus, in the present study we used a novel nuclear magnetic resonance (NMR)-based approach to profile the umbilical cord serum lipoproteins. Two-dimensional diffusion-ordered 1H-NMR spectroscopy showed that size, lipid content, number and concentration of particles within their subclasses were similar between offspring born to control (n = 74) and GDM (n = 62) mothers. Subsequent data stratification according to newborn birth-weight categories, i.e., small (n = 39), appropriate (n = 50) or large (n = 49) for gestational age (SGA, AGA and LGA, respectively), showed an interaction between GDM and birth-weight categories for intermediate-density lipoproteins (IDL)-cholesterol content and IDL- and low-density lipoproteins (LDL)-triglyceride content, and the number of medium very low-density lipoproteins (VLDL) and LDL particles specifically in AGA neonates. Moreover, in a 2-year follow-up study, we observed that small LDL particles were independently associated with offspring obesity at 2 years (n = 103). Collectively, our data demonstrate that GDM disturbs triglyceride and cholesterol lipoprotein content across birth-weight categories, with AGA neonates born to GDM mothers displaying a profile more similar to that of adults with dyslipidemia. Furthermore, an altered fetal lipoprotein pattern was associated with the development of obesity at 2 years.

A Reporting Tool for Adapted Guidelines in Health Care: The RIGHT-Ad@pt Checklist.

BACKGROUND: Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines. OBJECTIVE: To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for the reporting of adapted guidelines (including recommendations that have been adopted, adapted, or developed de novo), the RIGHT-Ad@pt checklist. DESIGN: A multistep process was followed to develop the checklist: establishing a working group, generating an initial checklist, optimizing the checklist (through an initial assessment of adapted guidelines, semistructured interviews, a Delphi consensus survey, an external review, and a final assessment of adapted guidelines), and approval of the final checklist by the working group. SETTING: International collaboration. PARTICIPANTS: A total of 119 professionals participated in the development process. MEASUREMENTS: Participants' consensus on items in the checklist. RESULTS: The RIGHT-Ad@pt checklist contains 34 items grouped in 7 sections: basic information (7 items); scope (6 items); rigor of development (10 items); recommendations (4 items); external review and quality assurance (2 items); funding, declaration, and management of interest (2 items); and other information (3 items). A user guide with explanations and real-world examples for each item was developed to provide a better user experience. LIMITATION: The RIGHT-Ad@pt checklist requires further validation in real-life use. CONCLUSION: The RIGHT-Ad@pt checklist has been developed to improve the reporting of adapted guidelines, focusing on the standardization, rigor, and transparency of the process and the clarity and explicitness of adapted recommendations. PRIMARY FUNDING SOURCE: None.

Coste-efectividad del desfibrilador automático implantable para la prevención primaria de la muerte súbita cardiaca / Cost-effectiveness of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death

Introducción y objetivos: El desfibrilador automático implantable (DAI) es una alternativa coste-efectiva para la prevención secundaria de la muerte súbita cardiaca, pero sigue habiendo dudas sobre su eficiencia en prevención primaria, sobre todo en pacientes con cardiopatía no isquémica.Métodos: Análisis de coste-utilidad del DAI más tratamiento médico convencional frente a tratamiento médico convencional para la prevención primaria de arritmias cardiacas desde la perspectiva del Sistema Nacional de Salud. Se simuló el curso de la enfermedad mediante modelos de Markov en pacientes con y sin cardiopatía isquémica. Los parámetros del modelo se basaron en los resultados obtenidos mediante metanálisis de los ensayos clínicos publicados entre 1996 y 2018 en los que se comparaba el DAI con el tratamiento médico convencional, los resultados de seguridad del ensayo DANISH y el análisis de la práctica clínica habitual en un hospital terciario.Resultados: Se estimó un beneficio del DAI sobre la muerte por cualquier causa con HR = 0,70 (IC95%, 0,58-0,85) en cardiopatía isquémica y HR = 0,79 (IC95%, 0,66-0,96) en no isquémica. La razón de coste-efectividad incremental estimada mediante análisis probabilístico fue de 19.171 euros/año de vida ajustado por calidad (AVAC) en pacientes con cardiopatía isquémica, 31.084 euros/AVAC en pacientes con miocardiopatía dilatada no isquémica y 23.230 euros/AVAC en los menores de 68 años.Conclusiones: La eficiencia del DAI monocameral ha mejorado en la última década y este resulta coste-efectivo para los pacientes con disfunción ventricular izquierda de origen isquémico o no isquémico menores de 68 años considerando una disposición a pagar 25.000 euros/AVAC. En pacientes no isquémicos mayores, la razón de coste-efectividad incremental estimada se sitúa alrededor de los 30.000 euros/AVAC (AU)

Introduction and objective: Implantable cardioverter-defibrillators (ICD) are a cost-effective alternative for secondary prevention of sudden cardiac death, but their efficiency in primary prevention, especially among patients with nonischemic heart disease, is still uncertain.Methods: We performed a cost-effectiveness analysis of ICD plus conventional medical treatment (CMT) vs CMT for primary prevention of cardiac arrhythmias from the perspective of the national health service. We simulated the course of the disease by using Markov models in patients with ischemic and nonischemic heart disease. The parameters of the model were based on the results obtained from a meta-analysis of clinical trials published between 1996 and 2018 comparing ICD plus CMT vs CMT, the safety results of the DANISH trial, and analysis of real-world clinical practice in a tertiary hospital.Results: We estimated that ICD reduced the likelihood of all-cause death in patients with ischemic heart disease (HR, 0.70; 95%CI, 0.58-0.85) and in those with nonischemic heart disease (HR, 0.79; 95%CI, 0.66–0.96). The incremental cost-effectiveness ratio (ICER) estimated with probabilistic analysis was €19 171/quality adjusted life year (QALY) in patients with ischemic heart disease and €31 084/QALY in those with nonischemic dilated myocardiopathy overall and €23 230/QALY in patients younger than 68 years.Conclusions: The efficiency of single-lead ICD systems has improved in the last decade, and these devices are cost-effective in patients with ischemic and nonischemic left ventricular dysfunction younger than 68 years, assuming willingness to pay as €25 000/QALY. For older nonischemic patients, the ICER was around €30 000/QALY (AU)

Cost-effectiveness of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death.

INTRODUCTION AND OBJECTIVES: Implantable cardioverter-defibrillators (ICD) are a cost-effective alternative for secondary prevention of sudden cardiac death, but their efficiency in primary prevention, especially among patients with nonischemic heart disease, is still uncertain. METHODS: We performed a cost-effectiveness analysis of ICD plus conventional medical treatment (CMT) vs CMT for primary prevention of cardiac arrhythmias from the perspective of the national health service. We simulated the course of the disease by using Markov models in patients with ischemic and nonischemic heart disease. The parameters of the model were based on the results obtained from a meta-analysis of clinical trials published between 1996 and 2018 comparing ICD plus CMT vs CMT, the safety results of the DANISH trial, and analysis of real-world clinical practice in a tertiary hospital. RESULTS: We estimated that ICD reduced the likelihood of all-cause death in patients with ischemic heart disease (HR, 0.70; 95%CI, 0.58-0.85) and in those with nonischemic heart disease (HR, 0.79; 95%CI, 0.66-0.96). The incremental cost-effectiveness ratio (ICER) estimated with probabilistic analysis was €19 171/quality adjusted life year (QALY) in patients with ischemic heart disease and €31 084/QALY in those with nonischemic dilated myocardiopathy overall and €23 230/QALY in patients younger than 68 years. CONCLUSIONS: The efficiency of single-lead ICD systems has improved in the last decade, and these devices are cost-effective in patients with ischemic and nonischemic left ventricular dysfunction younger than 68 years, assuming willingness to pay as €25 000/QALY. For older nonischemic patients, the ICER was around €30 000/QALY.

The angiogenic properties of human amniotic membrane stem cells are enhanced in gestational diabetes and associate with fetal adiposity.

BACKGROUND: An environment of gestational diabetes mellitus (GDM) can modify the phenotype of stem cell populations differentially according to their placental localization, which can be useful to study the consequences for the fetus. We sought to explore the effect of intrauterine GDM exposure on the angiogenic properties of human amniotic membrane stem cells (hAMSCs). METHODS: We comprehensively characterized the angiogenic phenotype of hAMSCs isolated from 14 patients with GDM and 14 controls with normal glucose tolerance (NGT). Maternal and fetal parameters were also recorded. Hyperglycemia, hyperinsulinemia and palmitic acid were used to in vitro mimic a GDM-like pathology. Pharmacological and genetic inhibition of protein function was used to investigate the molecular pathways underlying the angiogenic properties of hAMSCs isolated from women with GDM. RESULTS: Capillary tube formation assays revealed that GDM-hAMSCs produced a significantly higher number of nodes (P = 0.004), junctions (P = 0.002) and meshes (P < 0.001) than equivalent NGT-hAMSCs, concomitant with an increase in the gene/protein expression of FGFR2, TGFBR1, SERPINE1 and VEGFA. These latter changes were recapitulated in NGT-hAMSCs exposed to GDM-like conditions. Inhibition of the protein product of SERPINE1 (plasminogen activator inhibitor 1, PAI-1) suppressed the angiogenic properties of GDM-hAMSCs. Correlation analyses revealed that cord blood insulin levels in offspring strongly correlated with the number of nodes (r = 0.860; P = 0.001), junctions (r = 0.853; P = 0.002) and meshes (r = 0.816; P = 0.004) in tube formation assays. Finally, FGFR2 levels correlated positively with placental weight (r = 0.586; P = 0.028) and neonatal adiposity (r = 0.496; P = 0.014). CONCLUSIONS: GDM exposure contributes to the angiogenic abilities of hAMSCs, which are further related to increased cord blood insulin and fetal adiposity. PAI-1 emerges as a potential key player of GDM-induced angiogenesis.

Current practices and challenges in adaptation of clinical guidelines: a qualitative study based on semistructured interviews.

OBJECTIVE: This study aims to better understand the current practice of clinical guideline adaptation and identify challenges raised in this process, given that published adapted clinical guidelines are generally of low quality, poorly reported and not based on published frameworks. DESIGN: A qualitative study based on semistructured interviews. We conducted a framework analysis for the adaptation process, and thematic analysis for participants' views and experiences about adaptation process. SETTING: Nine guideline development organisations from seven countries. PARTICIPANTS: Guideline developers who have adapted clinical guidelines within the last 3 years. We identified potential participants through published adapted clinical guidelines, recommendations from experts, and a review of the Guideline International Network Conference attendees' list. RESULTS: We conducted ten interviews and identified nine adaptation methodologies. The reasons for adapting clinical guidelines include developing de novo clinical guidelines, implementing source clinical guidelines, and harmonising and updating existing clinical guidelines. We identified the following core steps of the adaptation process (1) selection of scope and source guideline(s), (2) assessment of source materials (guidelines, recommendations and evidence level), (3) decision-making process and (4) external review and follow-up process. Challenges on the adaptation of clinical guidelines include limitations from source clinical guidelines (poor quality or reporting), limitations from adaptation settings (lacking resources or skills), adaptation process intensity and complexity, and implementation barriers. We also described how participants address the complexities and implementation issues of the adaptation process. CONCLUSIONS: Adaptation processes have been increasingly used to develop clinical guidelines, with the emergence of different purposes. The identification of core steps and assessment levels could help guideline adaptation developers streamline their processes. More methodological research is needed to develop rigorous international standards for adapting clinical guidelines.

Teaching and learning how to make informed health choices: Protocol for a context analysis in Spanish primary schools.

Introduction The Informed Health Choices (IHC) project developed learning resources to teach primary school children (10 to 12-year-olds) to assess treatment claims and make informed health choices. The aim of our study is to explore the educational context for teaching and learning critical thinking about health in Spanish primary schools. Methods During the 2020-2021 school year, we will conduct 1) a systematic assessment of educational documents and resources, and 2) semi-structured interviews with key education and health stakeholders. In the systematic assessment of educational documents and resources, we will include state and autonomous communities' curriculums, school educational projects, and commonly used textbooks and other health teaching materials. In the semi-structured interviews, we will involve education and health policy makers, developers of learning resources, developers of health promotion and educational interventions, head teachers, teachers, families, and paediatric primary care providers. We will design and pilot a data extraction form and a semi-structured interview guide to collect the data. We will perform a quantitative and a qualitative analysis of the data to explore how critical thinking about health is being taught and learned in Spanish primary schools. Conclusion We will identify opportunities for and barriers to teaching and learning critical thinking about health in Spanish primary schools. We will formulate recommendations-for both practice and research purposes-on how to use, adapt (if needed), and implement the IHC resources in this context.

What Influences the Sustainable Food Consumption Behaviours of University Students? A Systematic Review.

Objectives: Global environmental challenges demand sustainable behaviours and policies to protect human and planetary health. We aimed to summarize the evidence about the factors related to Sustainable Food Consumption (SFC) behaviours of university students, and to propose an operational categorization of SFC behaviours. Methods: Seven databases were searched for observational studies evaluating Sustainable Food Consumption (SFC) among university students and that reported at least one behavioural outcome measure. Qualitative synthesis was conducted, and PRISMA guidelines for reporting were followed. Results: Out of 4,479 unique references identified, 40 studies were selected. All studies examined personal factors, while 11 out of 40 also measured social or situational factors. Except for food waste, females had higher levels of SFC behaviours, but situational factors moderated this association. Knowledge and attitudes showed mixed results. Overall, sustainable food consumers reported healthier lifestyles. Conclusions: Healthy lifestyle of sustainable food consumers suggests possible synergies between human health and sustainability in terms of motivations for food choice. Moderation effects of social and situational factors on personal factors reveal opportunities to design and examine the effects of choice architecture interventions.

Next Generation Cytogenetics in Myeloid Hematological Neoplasms: Detection of CNVs and Translocations.

Conventional cytogenetics are the gold standard for the identification of chromosomal alterations recurrent in myeloid neoplasms. Some next-generation sequencing (NGS) panels are designed for the detection of copy number variations (CNV) or translocations; however, their use is far from being widespread. Here we report on the results of a commercial panel including frequent mutations, CNVs and translocations in myeloid neoplasms. Frequent chromosomal alterations were analyzed by NGS in 135 patients with myeloid neoplasms and three with acute lymphoblastic leukemia. NGS analysis was performed using the enrichment-capture Myeloid Neoplasm-GeneSGKit (Sistemas Genómicos, Spain) gene panel including 35 genes for mutational analysis and frequent CNVs and translocations. NGS results were validated with cytogenetics and/or MLPA when possible. A total of 66 frequent alterations included in NGS panel were detected, 48 of them detected by NGS and cytogenetics. Ten of them were observed only by cytogenetics (mainly trisomy 8), and another eight only by NGS (mainly deletion of 12p). Aside from this, 38 secondary CNVs were detected in any of the genes included mainly for mutational analysis. NGS represents a reliable complementary source of information for the analysis of CNVs and translocations. Moreover, NGS could be a useful tool for the detection of alterations not observed by conventional cytogenetics.

Benefits and harms of breast cancer mammography screening for women at average risk of breast cancer: A systematic review for the European Commission Initiative on Breast Cancer.

OBJECTIVES: Mammography screening is generally accepted in women aged 50-69, but the balance between benefits and harms remains controversial in other age groups. This study systematically reviews these effects to inform the European Breast Cancer Guidelines. METHODS: We searched PubMed, EMBASE and Cochrane Library for randomised clinical trials (RCTs) or systematic reviews of observational studies in the absence of RCTs comparing invitation to mammography screening to no invitation in women at average breast cancer (BC) risk. We extracted data for mortality, BC stage, mastectomy rate, chemotherapy provision, overdiagnosis and false-positive-related adverse effects. We performed a pooled analysis of relative risks, applying an inverse-variance random-effects model for three age groups (<50, 50-69 and 70-74). GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used to assess the certainty of evidence. RESULTS: We identified 10 RCTs including 616,641 women aged 38-75. Mammography reduced BC mortality in women aged 50-69 (relative risk (RR) 0.77, 95%CI (confidence interval) 0.66-0.90, high certainty) and 70-74 (RR 0.77, 95%CI 0.54-1.09, high certainty), with smaller reductions in under 50s (RR 0.88, 95%CI 0.76-1.02, moderate certainty). Mammography reduced stage IIA+ in women 50-69 (RR 0.80, 95%CI 0.64-1.00, very low certainty) but resulted in an overdiagnosis probability of 23% (95%CI 18-27%) and 17% (95%CI 15-20%) in under 50s and 50-69, respectively (moderate certainty). Mammography was associated with 2.9% increased risk of invasive procedures with benign outcomes (low certainty). CONCLUSIONS: For women 50-69, high certainty evidence that mammography screening reduces BC mortality risk would support policymakers formulating strong recommendations. In other age groups, where the net balance of effects is less clear, conditional recommendations will be more likely, together with shared decision-making.

Healthcare professionals' opinions, barriers and facilitators towards low-value clinical practices in the hospital setting / Opiniones, barreras y facilitadores de los profesionales de la salud hacia las prácticas clínicas de poco valor en el ámbito hospitalario

OBJECTIVE: To explore healthcare professionals' opinions about low-value practices, identify practices of this kind possibly present in the hospital and barriers and facilitators to reduce them. Low-value practices include those with little or no clinical benefit that may harm patients or lead to a waste of resources. METHOD: Using a mixed methodology, we carried out a survey and two focus groups in a tertiary hospital. In the survey, we assessed doctors' agreement, subjective adherence and perception of usefulness of 134 recommendations to reduce low-value practices from local and international initiatives. We also identified low-value practices possibly present in the hospital. In the focus groups with professionals from surgical and medical fields, using a phenomenological approach, we identified additional low-value practices, barriers and facilitators to reduce them. RESULTS: 169 doctors of 25 specialties participated (response rate: 7%-100%). Overall agreement with recommendations, subjective adherence and usefulness were 83%, 90% and 70%, respectively. Low-value practices form 22 recommendations (16%) were considered as possibly present in the hospital. In the focus groups, the professionals identified seven more. Defensive medicine and scepticism due to contradictory evidence were the main barriers. Facilitators included good leadership and coordination between professionals. CONCLUSIONS: High agreement with recommendations to reduce low-value practices and high perception of usefulness reflect great awareness of low-value care in the hospital. However, there are several barriers to reduce them. Interventions to reduce low-value practices should foster confidence in decision-making processes between professionals and patients and provide trusted evidence

OBJETIVO: Explorar las opiniones de profesionales sanitarios sobre las prácticas de poco valor, identificar aquellas posiblemente presentes en el hospital y las barreras y los facilitadores para reducirlas. Las prácticas de poco valor incluyen aquellas con poco beneficio clínico que pueden perjudicar a los pacientes o desperdiciar recursos. MÉTODO: Usando una metodología mixta se llevaron a cabo una encuesta y varios grupos focales en un hospital terciario. En la encuesta se evaluó el grado de acuerdo, la adherencia subjetiva y la percepción de utilidad de 134 recomendaciones para reducir las prácticas de poco valor de iniciativas locales e internacionales, y se identificaron aquellas que podrían estar realizándose en el hospital. En dos grupos focales con profesionales de campos médicos y quirúrgicos, utilizando un enfoque fenomenológico, se identificaron prácticas de poco valor adicionales, barreras y facilitadores para reducirlas. RESULTADOS: En la encuesta participaron 169 médicos de 25 especialidades (tasa de respuesta: 7-100%). El acuerdo con las recomendaciones, la adherencia subjetiva y la utilidad fueron del 83%, el 90% y el 70%, respectivamente. Se identificaron prácticas de poco valor de 22 recomendaciones (16%) posiblemente presentes en el hospital. En los grupos focales se identificaron siete prácticas de poco valor adicionales; la medicina defensiva y el escepticismo debido a evidencia contradictoria como principales barreras; y un buen liderazgo y la coordinación entre profesionales como facilitadores. CONCLUSIONES: El alto grado de acuerdo con las recomendaciones para reducir las prácticas de poco valor y la alta percepción de utilidad reflejan una gran concienciación sobre este problema en el hospital. Sin embargo, existen numerosas barreras para eliminarlas. Las intervenciones para reducirlas deberían fomentar la confianza en la toma de decisiones entre profesionales y pacientes, y proporcionar una evidencia confiable

COVID-19 coagulopathy: An in-depth analysis of the coagulation system.

BACKGROUND: Abnormal coagulation parameters have been reported in COVID-19-infected patients. Although the underlying mechanism of COVID-19 coagulopathy remains unknown, it has been suggested to be a form of disseminated intravascular coagulation (DIC). OBJECTIVES: The aim of our study was to analyze the coagulation parameters of patients with COVID-19, determine whether coagulation factors consumption occurs and identify potential prognostic biomarkers of the disease. PATIENTS/METHODS: Blood samples from hospitalized patients with COVID-19 pneumonia were collected. We performed basic coagulation tests and quantification of coagulation factors and physiological inhibitor proteins. Laboratory data were compared with clinical data and outcomes. RESULTS: The study involved 206 patients (63.6% male). D-dimer was particularly elevated (median 450 ng/mL; IQR 222.5-957.3). Free protein S levels were below the normal range (median 56.6%; IQR: 43.6-68.9), and factor VIII showed an increasing trend (median 173.4%; IQR: 144.1-214.9). However, all coagulation factors were within normal limits. We found no correlation between abnormal coagulation parameters and thrombosis, except for higher D-dimer (HR 1.99; 95% CI 1.3-3.1; P = .002). CONCLUSIONS: COVID-19 is associated with coagulopathy that correlates with poor prognosis. However, we did not demonstrate a consumption of coagulation factors, as seen in DIC.

The UpPriority tool was developed to guide the prioritization of clinical guideline questions for updating.

OBJECTIVE: The objective of the study is to develop a pragmatic tool to prioritize clinical guideline (CG) questions for updating, the UpPriority tool. STUDY DESIGN AND SETTING: The development of this tool consisted of the following: (1) establishment of the working group, (2) generation of the initial version, (3) optimization of the tool (including an initial feasibility test, semistructured interviews, Delphi consensus survey, second feasibility test, external review, and pilot test), and (4) approval of the final version. RESULTS: A total of 87 participants including methodologists, clinicians, and other relevant stakeholders contributed to the development of the UpPriority tool. The tool consists of six items: (1) impact of outdated recommendations on safety, (2) availability of new relevant evidence, (3) context relevance of the clinical question, (4) methodological applicability of the clinical question, (5) user's interest, and (6) impact on access to health care. The UpPriority tool includes detailed guidance for using the tool and rating each item (using a 7-point Likert scale), for calculating and ranking the questions, and for summarizing results. CONCLUSION: The UpPriority tool could be useful for standardizing prioritization processes when updating CGs and for fostering more efficient use of resources in the CG field.

Moderately elevated first trimester fasting plasma total homocysteine is associated with increased probability of miscarriage. The Reus-Tarragona Birth Cohort Study.

The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n = 544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded. Miscarriages were diagnosed by ultrasound scan and gestational age at the time of miscarriage estimated by embryo size, where possible. Cases in which blood samples were collected more than a week after the miscarriage, or the miscarriage was of known cause, were excluded. Fasting plasma folate, vitamin B12, tHcy, cotinine (biomarker of smoking), red blood cell (RBC) folate, MTHFR 677C > T (rs1801133) and SLC19A1 80G>A (rs1051266) genotypes were determined. The exposed group consisted of participants with first trimester tHcy ≥ P90 (7.1 µmol/L) (n = 57) and unexposed of those with tHcy < P90 (n = 487). Adherence to folic acid supplement recommendations, plasma folate, plasma vitamin B12, RBC folate and prevalence of optimal RBC folate status (≥ 906 µmol/L) were lower in the exposed compared to unexposed group. The prevalences of the MTHFR 677 TT genotype and miscarriage were higher in the exposed group. The relative risks (95% CI) of pregnancy ending in miscarriage were 2.5 (1.1, 5.7) and 2.1 (1.0, 4.5) for participants in the high tHcy and suboptimal RBC folate groups (compared to the reference groups) respectively. Adherence to folic acid supplement recommendations was positively associated, while the MTHFR 677 TT versus CC genotype and smoking versus non-smoking were negatively associated, with RBC folate status.

The effect of prenatal smoke exposure on child neuropsychological function: a prospective mother-child cohort study.

Objective: To study prospectively the effect of prenatal smoke exposure (PSE) on child neuropsychological function and intelligence quotient (IQ).Background: PSE has been associated with adverse effects on child neurodevelopment. However, some studies reported that these associations disappear after adjustment for potential confounders.Methods: A cohortof 248 mothers-child dyad was followed from the first trimester of pregnancy until children were 7.5 years old. PSE was recorded during pregnancy by questionnaire and plasma cotinine. The Wechsler Intelligence Scale for Children, the Neuropsychological Assessment of Executive Functions for Children (ENFEN) and the School Neuropsychological Maturity Questionnaire were administered at 7.5 years of age. The effect of PSE on child IQ and neuropsychological function was assessed with ANCOVA, adjusting for obstetric, neonatal and sociodemographic factors.Results: Children whose mothers smoked throughout pregnancy scored lower in interference (ENFEN) compared to unexposed children (F = 4.1; p = .008). The results showed no differences in other executive functions, verbal and visual memory and IQ between the PSE groups.Conclusion: PSE had little effect on child neuropsychological outcome and was limited to mental flexibility. Nevertheless, these findings support further efforts aimed at encouraging mothers to quit smoking in pregnancy.