[Managing Superwarfarin Poisoning: A Challenging Case]. / Relato de caso de intoxicación con superwarfarinas: un desafío terapéutico.

Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a 42-year-old man who ingested a toxic dose of rodenticide in a suicide attempt, evolving with epistaxis, INR of 11.6, and needing hospitalization. For seven days, serial controls of coagulation tests were carried out, with optimization of different doses of Vitamin K supplementation. The case highlights this type of anticoagulant's potency and prolonged half-life (approximately six weeks), which requires regular clinical control and satisfactory treatment adherence.

Dermoscopy of Juvenile Xanthogranuloma.

BACKGROUND: Dermoscopy is useful for the evaluation of juvenile xanthogranuloma (JXG). The classical "setting sun" pattern is characteristic of JXG, but its sensibility appears to be limited. An extensive description of other dermoscopic findings is not available in the literature. OBJECTIVES: The aim of this study was to valuate and describe the clinical and dermoscopic characteristics of a series of JXG cases. METHODS: This is a retrospective descriptive study, including cases with histopathologic diagnosis of JXG, and the availability of clinical and dermoscopic images, assessed for the presence of dermoscopic features based on the available literature. RESULTS: A total of 17 lesions were analyzed. 70.6% showed global symmetry, 35.3% presented the typical "setting sun" pattern. All lesions showed yellow-orange and/or pink-red structureless color. Other dermoscopic features were yellow globules (35.3%), shiny white streaks (23.5%), brown globules (17.6%), pale-brown network (11.8%), negative network (11.8%), erosion/ulceration (11.8%), rosettes (5.9%), and hemorrhage (5.9%). Scales were seen in 64.7% of patients. Vascular structures were observed in all the lesions, mostly in an irregular distribution (76.5%). The observed vessel types were dotted (52.9%), linear (52.9%), branching-arboriform (29.4%), comma-like (23.5%), hairpin-like (17.6%), globular (17.6%), coiled (11.8%), and milky-red globules (5.9%). CONCLUSIONS: Symmetry, yellow/orange-pink/red color, yellow globules, shiny white streaks, and irregularly distributed different types of vascular structures are the main dermoscopic features of JXG. This is the largest dermoscopic registry of JXG published to date.

Microbial electrolysis cells for return flow: Simultaneous nitrogen and carbon removal.

The concentration of solids in secondary sludge before anaerobic digestion in a wastewater treatment plant, bring about the production of a return flow, which contains high concentrations of all the common pollutant parameters. This return flow could unfavourably affect the performance of the processes and effluent quality of the waterline. Here, we report the utilisation of three similar microbial electrolysis cells reactors that performs simultaneous carbon and nitrogen removal to reduce the impact of the return flow in the plant. The result of the batch-fed (72 h) experiment showed COD and total nitrogen removal efficiencies that reached 90% and 80%, respectively, supporting the premise that return flows are suitable substrates for a bioelectrochemical treatment. The three reactors followed similar trends, showing good replicability and confirming the potential of MECs as a feasible technology for return flow treatment. Furthermore, when cathodic conversion efficiency was higher than 80%, the pure hydrogen production allows to recover the electric energy consumption, indicating that the system could be theoretically energy neutral.

[Quality of life in people with depression and physical comorbidity from a gender perspective]. / Calidad de vida en personas con depresión y comorbilidad física desde una perspectiva de género.

OBJECTIVE: The aim of the study is to describe from a gender perspective how people with depression and physical comorbidity perceive their quality of life. The study included 380 people over 49 years of age with at least one of the following pathologies: diabetes, chronic obstructive pulmonary disease and ischemic heart disease. Participants were recruited from 31 teams the primary care of in Catalonia. Quality of life was measured using the EuroQol Scale. In addition, sociodemographic variables were collected, as well as the severity of depression, the index of economic deprivation and area of residence. The adjusted relationship between sex and dimensions of quality of life was assessed by means of multivariate logistic regression. RESULTS: 81.3% were women; the mean age was 68.4 years (SD: 8.8). The mean on the Visual Analogue Scale was 57.8 (SD: 17.4) in men and 55.8 (SD: 18.6) in women. The mean of the EQ-Health Index was 0.74 (SD: 0.17) in men and 0.65 (SD: 0.2) in women (p = 0.001). The probability of having problems of the EQ-5D showed sex as the most important factor (woman = 1/man = 0) in: self-care OR: 2.29 (95% CI 1.04-5.07) and daily activities OR: 3.09 (95% CI 1.67-5.71). Mobility was associated with age OR: 1.87 (95% CI 1.22-2.86), pain with area of residence OR: 2.51 (95% CI 1.18-5,34) and the BDI with anxiety/depression OR: 4,77 (95% CI 1.77-12,88). CONCLUSION: The perception quality of life of women with depression and physical comorbidity is lower than that of men and, in both cases, it is lower than that of the general population.

[Translation and cross-cultural adaptation into Spanish, Catalan and Galician of the Hopkins Symptom Checklist-25 to identify depression in Primary Care]. / Traducción y adaptación transcultural al español, catalán y gallego de la escala Hopkins Symptom Checklist-25 para la detección de depresión en Atención Primaria.

AIM: To describe the translation and cross-cultural adaptation process of the Hopkins Symptom Checklist-25 (HSCL-25) scale into Spanish, Catalan and Galician. DESIGN: Translation, cross-cultural adaption and comprehensibility analysis through cognitive debriefing. LOCATION: Research Units of Primary Care in Barcelona and Vigo. PARTICIPANTS: Family doctors and Primary Care patients. MAIN MEASUREMENTS: Following the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR): 1) Direct translation. 2) Pilot study based on Delphi methodology with family doctors. 3) Back-translation. 4) Equivalence analysis. 5) Comprehension analysis of versions obtained in Spanish, Catalan and Galician through cognitive debriefing in a sample of patients. 6) Transcultural harmonization. RESULTS: 73 family doctors participated in the Delphi study. The consensus was established in the first round for the Spanish and Catalan translations, and in the second round for the Galician. The back-translations were similar in all 3languages. All versions were equivalent between them and compared to the original English version. In the cognitive interview, 10 patients participated for each language, without modifying the writing of the items. CONCLUSIONS: The translations of the HSCL-25 scale in Spanish, Catalan and Galician are semantically and conceptually equivalent to the original version. Translations are understandable and well accepted by patients.

Analysis of miRNA signatures in CSF identifies upregulation of miR-21 and miR-146a/b in patients with multiple sclerosis and active lesions.

BACKGROUND: MicroRNAs (miRNAs) have been reported as deregulated in active brain lesions derived from patients with multiple sclerosis (MS). In there, these post-transcriptional regulators may elicit very important effects but proper identification of miRNA candidates as potential biomarkers and/or therapeutic targets is scarcely available. OBJECTIVE: The aim of the study was to detect the presence of a set of candidate miRNAs in cell-free cerebrospinal fluid (CSF) and to determine their association with gadolinium-enhancing (Gd+) lesions in order to assess their value as biomarkers of MS activity. METHODS: Assessment of 28 miRNA candidates in cell-free CSF collected from 46 patients with MS (26 Gd+ and 20 Gd- patients) was performed by TaqMan assays and qPCR. Variations in their relative abundance were analyzed by the Mann-Whitney U test and further evaluated by receiver operating characteristic (ROC) analysis. Signaling pathways and biological functions of miRNAs were analyzed using bioinformatic tools (miRTarBase, Enrichr, REVIGO, and Cytoscape softwares). RESULTS: Seven out of 28 miRNA candidates were detected in at least 75% of CSF samples. Consistent increase of miR-21 and miR-146a/b was found in Gd+ MS patients. This increase was in parallel to the number of Gd+ lesions and neurofilament light chain (NF-L) levels. Gene Ontology enrichment analysis revealed that the target genes of these miRNAs are involved in biological processes of key relevance such as apoptosis, cell migration and proliferation, and in cytokine-mediated signaling pathways. CONCLUSION: Levels of miR-21 and miR-146a/b in cell-free CSF may represent valuable biomarkers to identify patients with active MS lesions.

Effectiveness of a psychoeducation group intervention conducted by primary healthcare nurses in patients with depression and physical comorbidity: study protocol for a randomized, controlled trial.

BACKGROUND: Depressive disorders are the third leading cause of consultation in primary care, mainly in patients with chronic physical illnesses. Studies have shown the effectiveness of group psychoeducation in reducing symptoms in depressive individuals. Our primary aim is to evaluate the effectiveness of an intervention based on a psychoeducational program, carried out by primary care nurses, to improve the remission/response rate of depression in patients with chronic physical illness. Secondarily, to assess the cost-effectiveness of the intervention, its impact on improving control of the physical pathology and quality of life, and intervention feasibility. METHODS/DESIGN: A multicenter, randomized, clinical trial, with two groups and one-year follow-up evaluation. Economic evaluation study. SUBJECTS: We will assess 504 patients (252 in each group) aged > 50 years assigned to 25 primary healthcare centers (PHC) from Catalonia (urban, semi-urban, and rural). Participants suffer from major depression (Beck depression inventory: BDI-II 13-28) and at least one of the following: type 2 diabetes mellitus, chronic obstructive pulmonary disease, asthma, and/or ischemic cardiopathy. Patients with moderate/severe suicide risk or severe mental disorders are excluded. Participants will be distributed randomly into the intervention group (IG) and control (CG). INTERVENTION: The IG will participate in the psychoeducational intervention: 12 sessions of 90 min, once a week led by two Primary Care (PC) nurses. The sessions will consist of health education regarding chronic physical illness and depressive symptoms. MAIN MEASUREMENTS: Clinical remission of depression and/or response to intervention (BDI-II). SECONDARY MEASUREMENTS: Improvement in control of chronic diseases (blood test and physical parameters), drug compliance (Morinsky-Green test and number of containers returned), quality of life (EQ-5D), medical service utilization (appointments and hospital admissions due to complications), and feasibility of the intervention (satisfaction and compliance). Evaluations will be blinded, and conducted at baseline, post-intervention, and 12 months follow-up. DISCUSSION: Results could be informative for efforts to prevent depression in patients with a chronic physical illness. TRIAL REGISTRATION: NCT03243799 (registration date August 9, 2017).

Promoting Diversity in the Clinical and Translational Research Workforce.

The positive impact of diversity in increasing the effectiveness of the research workforce has been undeniably demonstrated to be an essential element for achieving health equity. Diversity is also instrumental for the research workforce to advance discovery, eliminate health disparities, improve minority health and achieve effective patient-centered outcomes in the quest for better health. One of the sustainable ways to achieve diversity in the workforce is through training, education and career development of all interested individuals including minority, underserved, underrepresented and populations with special needs. A Hispanic public, academic health center, and a historically black private medical school, have joined efforts in this article to share their experiences in addressing diversity in the clinical and translational research workforce with grant support from the National Institutes of Health. The purpose of this paper is to describe how diversity has been achieved through a concerted effort to recruit and develop underrepresented junior faculty and doctoral candidates for successful careers in clinical and translational research focused on health disparities and minority health. We describe Initiatives designed to achieve diversity in recruitment and development of research teams, together with an evaluation of outcomes to determine the success of the program and its participants.

Cardiovascular risk assessment in patients with a severe mental illness: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular risk (CVR) has been observed to be higher in patients with severe mental illness (SMI) than in the general population. However, some studies suggest that CVR is not equally increased in different subgroups of SMI. The purposes of this review are to summarise CVR scores of SMI patients and to determine the differences in CVR between patients with different SMIs and between SMI patients and the control-population. METHODS: MEDLINE (via PubMed) was searched for literature published through August 28, 2014, followed by a snowball search in the Web of Science. Observational and experimental studies that reported CVR assessments in SMI patients using validated tools were included. The risk of bias was reported using STROBE and CONSORT criteria. Pooled continuous data were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Two reviewers independently selected studies, extracted data and assessed methodological quality. RESULTS: A total of 3,608 articles were identified, of which 67 full text papers were assessed for eligibility and 35 were finally included in our review, in which 12,179 psychiatric patients and 225,951 comparative patients had been assessed. The most frequent diagnoses were schizophrenia and related diagnoses (45.7%), depressive disorders (14.7%), SMI (11.4%) and bipolar disorders (8.6%). The most frequent CVR assessment tool used was the Framingham risk score. Subgroups analysis showed a higher CVR in schizophrenia than in depressive disorder or in studies that included patients with multiple psychiatric diagnoses (SMD: 0.63, 0.03, and 0.02, respectively). Six studies were included in the meta-analysis. Total overall CVR did not differ between SMI patients and controls (SMD: 0.35 [95% CI:-0.02 to 0.71], p = 0.06); high heterogeneity was observed (I (2) = 93%; p < 0.001). CONCLUSIONS: The summary of results from studies that assessed CVR using validated tools in SMI patients did not find sufficient data (except for limited evidence associated with schizophrenia) to permit any clear conclusions about increased CVR in this group of patients compared to the general population. The systematic review is registered in PROSPERO: CRD42013003898 .

[Inappropriate prescribing in polymedicated patients over 64 years-old in primary care]. / Prescripción inadecuada en pacientes polimedicados mayores de 64 años en atención primaria.

OBJECTIVE: To describe inappropriate prescribing (IP) in the polymedicated population over 64 years-old in primary care using the STOPP/START criteria. DESIGN: The study design was descriptive, cross-sectional and multicenter. LOCATION: Four urban primary care centers in Barcelona. Participants Patients over 64 years-old with more than 5 prescribed drugs for at least 6 months (n=467). Main measurements Major health problems, chronically prescribed drugs, and percentage of IP using the STOPP/START criteria were studied. Percentage of IP considered as the percentage of patients with at least one STOPP or START non-compliance criterion was calculated with a 95%CI. Chi-square was used for statistical analysis. RESULTS: The mean age was 77.3 (± 7.0 SD) with a mean of 8.9 (± 2.8 SD) prescribed drugs. IP was higher the greater the number of drugs prescribed (p<0,01). 326 patients (76.4% [95%CI: 72.2 to 80.6]) had at least one IP, according to STOPP/START criteria. STOPP IP affected 51.4% of the patients and START IP 53.6%. The most frequent causes of IP were antiplatelet agents, for both over-prescribing (10.2%) and omission (17.9%). Prolonged use of benzodiazepines (6.6%) and duplications (6.4%) followed in prevalence. CONCLUSIONS: IP in polymedicated patients in primary care was very high. IP was similar for drugs that should be withdrawn or started. The most common causes of IP were antiplatelet agents, benzodiazepines and drug duplication.

The effectiveness of lifestyle interventions to reduce cardiovascular risk in patients with severe mental disorders: meta-analysis of intervention studies.

Patients with severe mental illness have higher prevalences of cardiovascular risk factors (CRF). The objective is to determine whether interventions to modify lifestyles in these patients reduce anthropometric and analytical parameters related to CRF in comparison to routine clinical practice. Systematic review of controlled clinical trials with lifestyle intervention in Medline, Cochrane Library, Embase, PsycINFO and CINALH. Change in body mass index, waist circumference, cholesterol, triglycerides and blood sugar. Meta-analyses were performed using random effects models to estimate the weighted mean difference. Heterogeneity was determined using i(2) statistical and subgroups analyses. 26 studies were selected. Lifestyle interventions decrease anthropometric and analytical parameters at 3 months follow up. At 6 and 12 months, the differences between the intervention and control groups were maintained, although with less precision. More studies with larger samples and long-term follow-up are needed.

Cost-effectiveness and cost-utility study of a psychoeducational group intervention for people with depression and physical comorbidity in primary care.

OBJECTIVE: To evaluate the cost-effectiveness and cost-utility of a psychoeducational group intervention led by primary care (PC) nurses in relation to customary care to prevent the depression and improve quality of life in patients with physical comorbidity. DESIGN: Economic evaluation based on data from randomized, multicenter clinical trial with blind response variables and a one-year follow-up, carried in the context of the PSICODEP study. LOCATION: 7 PC teams from Catalonia. PARTICIPANTS: >50 year-old patients with depression and some physical comorbidity: diabetes mellitus type 2, ischemic heart disease, chronic obstructive pulmonary disease, and/or asthma. INTERVENTION: 12 psychoeducational group sessions, 1 per week, led by 2 PC nurses with prior training. MEASUREMENTS: Effectiveness: depression-free days (DFD) calculated from the BDI-II and quality-adjusted life years (QALYs) from the Euroqol-5D. Direct costs: PC visits, mental health, emergencies and hospitalizations, drugs. Indirect costs: days of temporary disability (TD). The incremental cost-effectiveness ratios (ICER), cost-effectiveness (ΔCost/ΔDLD) and cost-utility (ΔCost/ΔQALY) were estimated. RESULTS: The study includes 380 patients (intervention group [IG] = 204; control group [CG] = 176). 81.6% women; mean age 68.4 (SD = 8.8). The IG had a higher mean cost of visits, less of hospitalizations and less TD than the CG. The difference in costs between the IG and the CG was -357.95€ (95% CI: -2026.96 to 1311.06) at one year of follow-up. There was a mean of 11.95 (95% CI: -15.98 to 39.88) more DFD in the IG than in the CG. QALYs were similar (difference -0.01, 95% CI -0.04 to 0.05). The ICERs were 29.95€/DLD and 35,795€/QALY. CONCLUSIONS: Psychoeducational intervention is associated with an improvement in DFD, as well as a reduction in costs at 12 months, although not significantly. QALYs were very similar between groups.

Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.

The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes. Here we show that developmental genes and nearby clusters of CTCF sites cooperatively foster the robust insulation of regulatory domains. By genetically dissecting a couple of representative loci in mouse embryonic stem cells, we show that CTCF sites prevent undesirable enhancer-gene contacts (i.e. physical insulation), while developmental genes preferentially contribute to regulatory insulation through non-structural mechanisms involving promoter competition rather than enhancer blocking. Overall, our work provides important insights into the insulation of regulatory domains, which in turn might help interpreting the pathological consequences of certain structural variants.

[Effectiveness of a joint project between primary care and mental health to improve the recording of cardiovascular risk factors in patients with psychosis]. / Efectividad de un proyecto de colaboración entre atención primaria y salud mental para mejorar el registro de factores de riesgo cardiovascular en pacientes con psicosis.

OBJECTIVE: To evaluate the effectiveness of a joint team intervention between primary care (PC) and mental health (MH) to improve information on cardiovascular risk factors (CVRF) in psychotic patients. DESIGN: Multicenter before-after intervention study. LOCATION: Seven primary care and 2 mental health centers in Barcelona participated. PARTICIPANTS: All patients between 18-65 years old with a confirmed diagnosis of psychosis assigned to PC teams (n = 690) are included. INTERVENTION: Shared clinical sessions, developing a joint GP-MH protocol and implement it. VARIABLES: Gender, age, number of Appointments per center/year, smoking, blood pressure, body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, glucose, waist circumference (WC), Cardiovascular Risk. ANALYSIS: Comparison of CVRF records from 2008 to 2010 using statistical tests for paired data. Calculation of CVRF prevalence in accordance with metabolic syndrome criteria and the criteria for referral to GP. RESULTS: The mean age was 42.3 (SD 11.4) years, with 67% males. All CVRF significantly Increased in clinical notes, particularly all blood test parameters and WC. More than 35% of patients had a CVRF according to metabolic syndrome criteria. Criteria to refer to PC physician (2010) identified: obesity 51.9%, 23.9% hypertension, high cholesterol 20.4% and 11.6% diabetes. CONCLUSIONS: CVRF recording improvement. High percentage of patients needed GP intervention due to a CVRF.

COVID-19 Serological Study in Non-infected Vaccinated Subjects: Differences among Age, Sex, and Vaccine Brand.

OBJECTIVE: To evaluate IgG antibody levels against SARS-CoV-2 in non-infected vaccinated subjects among vaccine brand, sex, and age. METHODS: Abbott's AdviseDx SARS-CoV-2 IgG II immunoassay was used to measure IgG levels within 6-9 months after the second dose vaccination; level >50 AU/mL was classified as a positive test. RESULTS: Data of 183 non-infected vaccinated subjects was analyzed according to the vaccine brand, time after second vaccination, sex, and age. Bivariate analysis showed that receiving the Moderna brand vaccine, being female, and younger were associated with higher antibody levels, p<.001. Conversely, no differences were observed between the IgG antibody levels against SARS-CoV-2 and time after second vaccination (6-7 months as compared to 8-9 months), p=.49. CONCLUSION: After six to nine months post-vaccination, receiving the Moderna vaccine, being female, and being younger were significantly associated to higher IgG antibody levels to SARS-CoV-2 in non-infected vaccinated subjects.

miRNA Signature in CSF From Patients With Primary Progressive Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Primary progressive multiple sclerosis (PPMS) displays a highly variable disease progression with a characteristic accumulation of disability, what makes difficult its diagnosis and efficient treatment. The identification of microRNAs (miRNAs)-based signature for the early detection in biological fluids could reveal promising biomarkers to provide new insights into defining MS clinical subtypes and potential therapeutic strategies. The objective of this cross-sectional study was to describe PPMS miRNA profiles in CSF and serum samples compared with other neurologic disease individuals (OND) and relapsing-remitting MS (RRMS). METHODS: First, a screening stage analyzing multiple miRNAs in few samples using OpenArray plates was performed. Second, individual quantitative polymerase chain reactions (qPCRs) were used to validate specific miRNAs in a greater number of samples. RESULTS: A specific profile of dysregulated circulating miRNAs (let-7b-5p and miR-143-3p) was found downregulated in PPMS CSF samples compared with OND. In addition, in serum samples, miR-20a-5p and miR-320b were dysregulated in PPMS against RRMS and OND, miR-26a-5p and miR-485-3p were downregulated in PPMS vs RRMS, and miR-142-5p was upregulated in RRMS compared with OND. DISCUSSION: We described a 2-miRNA signature in CSF of PPMS individuals and several dysregulated miRNAs in serum from patients with MS, which could be considered valuable candidates to be further studied to unravel their actual role in MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that specific miRNA profiles accurately distinguish PPMS from RRMS and other neurologic disorders.

Inhibition of pro-inflammatory signaling in human primary macrophages by enhancing arginase-2 via target site blockers.

The modulation of macrophage phenotype from a pro-inflammatory to an anti-inflammatory state holds therapeutic potential in the treatment of inflammatory disease. We have previously shown that arginase-2 (Arg2), a mitochondrial enzyme, is a key regulator of the macrophage anti-inflammatory response. Here, we investigate the therapeutic potential of Arg2 enhancement via target site blockers (TSBs) in human macrophages. TSBs are locked nucleic acid antisense oligonucleotides that were specifically designed to protect specific microRNA recognition elements (MREs) in human ARG2 3' UTR mRNA. TSBs targeting miR-155 (TSB-155) and miR-3202 (TSB-3202) MREs increased ARG2 expression in human monocyte-derived macrophages. This resulted in decreased gene expression and cytokine production of TNF-α and CCL2 and, for TSB-3202, in an increase in the anti-inflammatory macrophage marker, CD206. Proteomic analysis demonstrated that a network of pro-inflammatory responsive proteins was modulated by TSBs. In silico bioinformatic analysis predicted that TSB-3202 suppressed upstream pro-inflammatory regulators including STAT-1 while enhancing anti-inflammatory associated proteins. Proteomic data were validated by confirming increased levels of sequestosome-1 and decreased levels of phosphorylated STAT-1 and STAT-1 upon TSB treatment. In conclusion, upregulation of Arg2 by TSBs inhibits pro-inflammatory signaling and is a promising novel therapeutic strategy to modulate inflammatory signaling in human macrophages.