Integración del modelo biopsicosocial en la implantación de Comprehensive Medication Management para pacientes tratados en una institución oncológica en Colombia / Biopsychosocial Model Integration in the implementation of Comprehensive Medication Management for patients treated in an oncological institution in Colombia

Introducción: Las personas con cáncer necesitan recibir cuidados enfocados en aspectos biopsi-cosociales considerando la experiencia con la medicación (MedExp), la evolución de esta enfermedad y la calidad de vida relacionada con la salud (CRVS). Se presentan los resultados del Compre-hensive Medication Management (CMM) implanta-do en una institución colombiana especializada en oncología. Método: Diseño cuali-cuantitativo mixto observacional, descriptivo y prospectivo. Los datos se obtuvieron mediante triangulación de técnicas cualitativas (entrevistas en profundidad y observación participante) y cuantitativas (entrevistas clínicas con cuestionarios validados). Las entrevistas fueron presenciales y telemáticas por la pandemia (febrero-octubre 2021). Según los estándares del CMM, se generó la historia farmacoterapéutica, se registró la información biopsicosocial y se analizó la MedExp y la CVRS utilizando Medicines Optimisation Software®. Resultados: Se evaluaron los estándares antes y después de su implantación. La valoración inicial tuvo un análisis DAFO (Debilidades, Amenazas, Fortalezas, Oportunidades) consensuando estrategias para desarrollar CMM. El servicio de oncología derivó 17 personas, 10 mujeres aceptaron participar. Se completaron 30 entrevistas recogiendo narrativas sobre experiencias, observaciones y datos clínicos contextualizados a partir de las que se realizaron intervenciones biopsicosociales. Se resolvieron 2 condiciones clínicas, 2 mejoraron, 7 permanecieron estables, 9 mejoraron parcialmente y 4 no tuvieron mejoría. Tras recibir CMM, las participantes mejoraron su autopercepción en salud, y mejoraron principalmente las dimensiones de movilidad, realización de actividades cotidianas y ansiedad/depresión. Conclusiones: En la implantación del CMM se integró el modelo biopsicosocial considerando las experiencias reales de padecer cáncer alcanzando mejoría en condiciones clínicas y en CVRS de las pacientes atendidas. (AU)

Introduction: People with cancer need to receive care focused on biopsychosocial aspects, consid-ering medication experience (MedExp), disease and illness progression, and health-related quality of life (HRQoL). The results of the Comprehensive Medication Management (CMM) implemented in a Colombian institution specialized in oncology are presented. Method: Mixed observational, descriptive, and pro-spective qualitative-quantitative design. Data were obtained by triangulating qualitative (in-depth inter-views and participant observation) and quantitative techniques (clinical interviews with validated ques-tionnaires). Data was collected through interviews carried out face-to-face and remotely due to the pandemic situation during February-October 2021. According to CMM standards, the pharmacothera-peutic history was obtained, recorded, and MedExp and HRQoL were analyzed using Medicines Optimi-zation Software®. Results: The standards of pharmaceutical care practice were established through the implemen-tation of a SWOT analysis to support care process. The oncology service referred 17 people; 10 women agreed to participate. Thirty interviews were completed collecting narratives about experiences, observations and contextualized clinical data from which biopsychosocial interventions were carried out. Clinical results obtained were: 2 clinical condi-tions resolved, 2 improved, 7 stable, 9 partially im-proved and 4 unimprovement. After receiving CMM, the participants improved their self-perception of health, and HRQoL dimensions of mobility, daily activities, and anxiety/depression improved. Conclusions: Through the implementing of CMM, clinical conditions related to the patients’ medica-tions were improved. Results guided the actions to be followed when implementing this biopsychoso-cial model in the institution. Providing benefits for patients and caregivers, in terms of avoiding the deterioration of quality of life despite suffering from of oncological diseases.

The Genomic Shock Hypothesis: Genetic and Epigenetic Alterations of Transposable Elements after Interspecific Hybridization in Plants.

Transposable elements (TEs) are major components of plant genomes with the ability to change their position in the genome or to create new copies of themselves in other positions in the genome. These can cause gene disruption and large-scale genomic alterations, including inversions, deletions, and duplications. Host organisms have evolved a set of mechanisms to suppress TE activity and counter the threat that they pose to genome integrity. These includes the epigenetic silencing of TEs mediated by a process of RNA-directed DNA methylation (RdDM). In most cases, the silencing machinery is very efficient for the vast majority of TEs. However, there are specific circumstances in which TEs can evade such silencing mechanisms, for example, a variety of biotic and abiotic stresses or in vitro culture. Hybridization is also proposed as an inductor of TE proliferation. In fact, the discoverer of the transposons, Barbara McClintock, first hypothesized that interspecific hybridization provides a "genomic shock" that inhibits the TE control mechanisms leading to the mobilization of TEs. However, the studies carried out on this topic have yielded diverse results, showing in some cases a total absence of mobilization or being limited to only some TE families. Here, we review the current knowledge about the impact of interspecific hybridization on TEs in plants and the possible implications of changes in the epigenetic mechanisms.

Absence of major epigenetic and transcriptomic changes accompanying an interspecific cross between peach and almond.

Hybridization has been widely used in breeding of cultivated species showing low genetic variability, such as peach (Prunus persica). The merging of two different genomes in a hybrid often triggers a so-called "genomic shock" with changes in DNA methylation and in the induction of transposable element expression and mobilization. Here, we analysed the DNA methylation and transcription levels of transposable elements and genes in leaves of Prunus persica and Prunus dulcis and in an F1 hybrid using high-throughput sequencing technologies. Contrary to the "genomic shock" expectations, we found that the overall levels of DNA methylation in the transposable elements in the hybrid are not significantly altered compared with those of the parental genomes. We also observed that the levels of transcription of the transposable elements in the hybrid are in most cases intermediate as compared with that of the parental species and we have not detected cases of higher transcription in the hybrid. We also found that the proportion of genes whose expression is altered in the hybrid compared with the parental species is low. The expression of genes potentially involved in the regulation of the activity of the transposable elements is not altered. We can conclude that the merging of the two parental genomes in this Prunus persica x Prunus dulcis hybrid does not result in a "genomic shock" with significant changes in the DNA methylation or in the transcription. The absence of major changes may facilitate using interspecific peach x almond crosses for peach improvement.

Síndrome de Wellens: o infarto agudo do miocárdio iminente / Wellens Syndrome: impending acute myocardial infarction

A síndrome de Wellens foi descrita em 1982 por Zwaan, Bär e Wellens. No eletrocardiograma, observam-se alterações morfológicas da onda T nas derivações precordiais, sugerindo estenose proximal grave da artéria coronária descendente anterior que representa iminente risco de infarto agudo do miocárdio e/ou morte súbita, com discreta ou nenhuma alteração da troponina sérica. Seu reconhecimento antecipado e a abordagem com reperfusão miocárdica precoce evitam desfechos desfavoráveis. A intervenção coronária percutânea e a revascularização miocárdica cirúrgica são as estratégias mais utilizadas para tratamento. Os autores descrevem dois casos de síndrome de Wellens tipos A e B tratados por diferentes estratégias de reperfusão.

Wellens syndrome was described by Zwaan, Bär and Wellens, in 1982. On the electrocardiogram, T wave morphological alterations are observed in precordial leads, suggesting severe proximal stenosis of the left anterior descending coronary artery and an imminent risk of acute myocardial infarction and/or sudden death, with slight or no alteration in serum troponin. Its early recognition and management with early myocardial reperfusion avoid unfavorable outcomes. Percutaneous coronary intervention and surgical myocardial revascularization are the most used strategies for treatment. The authors describe two cases of types A and B Wellens syndrome treated with different reperfusion strategies.

Genome-wide identification of Reverse Transcriptase domains of recently inserted endogenous plant pararetrovirus (Caulimoviridae).

Endogenous viral elements (EVEs) are viral sequences that have been integrated into the nuclear chromosomes. Endogenous pararetrovirus (EPRV) are a class of EVEs derived from DNA viruses of the family Caulimoviridae. Previous works based on a limited number of genome assemblies demonstrated that EPRVs are abundant in plants and are present in several species. The availability of genome sequences has been immensely increased in the recent years and we took advantage of these resources to have a more extensive view of the presence of EPRVs in plant genomes. We analyzed 278 genome assemblies corresponding to 267 species (254 from Viridiplantae) using tBLASTn against a collection of conserved domains of the Reverse Transcriptases (RT) of Caulimoviridae. We concentrated our search on complete and well-conserved RT domains with an uninterrupted ORF comprising the genetic information for at least 300 amino acids. We obtained 11.527 sequences from the genomes of 202 species spanning the whole Tracheophyta clade. These elements were grouped in 57 clusters and classified in 13 genera, including a newly proposed genus we called Wendovirus. Wendoviruses are characterized by the presence of four open reading frames and two of them encode for aspartic proteinases. Comparing plant genomes, we observed important differences between the plant families and genera in the number and type of EPRVs found. In general, florendoviruses are the most abundant and widely distributed EPRVs. The presence of multiple identical RT domain sequences in some of the genomes suggests their recent amplification.

Anemia in patients with high-risk acute coronary syndromes admitted to Intensive Cardiac Care Units.

BACKGROUND: Little information exists about the role of anemia in patients with acute coronary syndromes (ACS) admitted to Intensive Cardiac Care Units (ICCU). The aim of this study was to assess the prevalence of anemia and its impact on management and outcomes in this clinical setting. METHODS: All consecutive patients admitted to eight different ICCUs with diagnosis of non-ST segment elevation ACS (NSTEACS) were prospectively included. Anemia was defined as hemoglobin < 130 g/L in men and < 120 g/L in women. The association between anemia and mortality or readmission at six months was assessed by the Cox regression method. RESULTS: A total of 629 patients were included. Mean age was 66.6 years. A total of 197 patients (31.3%) had anemia. Coronary angiography was performed in most patients (96.2%). Patients with anemia were significantly older, with a higher prevalence of comorbidities, poorer left ventricle ejection fraction and higher GRACE score values. Patients with anemia underwent less often coronary angiography, but underwent more often intraaortic counterpulsation, non-invasive mechanical ventilation and renal replacement therapies. Both ICCU and hospital stay were significantly longer in patients with anemia. Both the incidence of mortality (HR = 3.36, 95% CI: 1.43-7.85, P = 0.001) and the incidence of mortality/readmission were significantly higher in patients with anemia (HR = 2.80, 95% CI: 2.03-3.86, P = 0.001). After adjusting for confounders, the association between anemia and mortality/readmission remained significant (P = 0.031). CONCLUSIONS: Almost one of three NSTEACS patients admitted to ICCU had anemia. Most patients underwent coronary angiography. Anemia was independently associated to poorer outcomes at 6 months.

Comorbidity and low use of new antiplatelets in acute coronary syndrome.

INTRODUCTION: Despite the use of the new generation P2Y12 inhibitors (Ticagrelor and Prasugrel) with aspirin is the recommended therapy in acute NSTE-ACS patients, their current use in clinical practice remains quite low and might be related, among several variables, with increased comorbidity burden. We aimed to assess the prevalence of these treatments and whether their use could be associated with comorbidity. METHOD: A multicentric prospective registry was conducted at 8 Cardiac Intensive Care Units (October 2017-April 2018) in patients admitted with non ST elevation myocardial infarction. Antithrombotic treatment was recorded and the comorbidity risk was assessed using the Charlson Comorbidity Index. We created a multivariate model to identify the independent predictors of the use of new inhibitors of P2Y12. RESULTS: A total of 629 patients were included, median age 67 years, 23.2% women, 359 patients (57.1%) treated with clopidogrel and 40.6% with new P2Y12 inhibitors: ticagrelor (228 patients, 36.2%) and prasugrel (30 patients, 4.8%). Among the patients with very high comorbidity (Charlson Score > 6) clopidogrel was the drug of choice (82.6%), meanwhile in patients with low comorbility (Charlson Score 0-1) was the ticagrelor or prasugrel (63.6%). Independent predictors of the use of ticagrelor or prasugrel were a low Charlson Comorbidity Index, a low CRUSADE score and the absence of prior bleeding. CONCLUSION: Antiplatelet treatment with Ticagrelor or Pasugrel was low in patients admitted with NSTE-ACS. Comorbidity calculated with Charlson Comorbidity Index was a powerful predictor of the use of new generation P2Y12 inhibitors in this population.

Diabetes mellitus is not independently associated with mortality in elderly patients with ST-segment elevation myocardial infarction. Insights from the Codi Infart registry.

BACKGROUND: Diabetes mellitus predicts poorer outcomes in patients with acute coronary syndrome (ACS), but the magnitude of this association in patients at older ages remains controversial. METHODS: Data were extracted from the Codi Infart database. All consecutive patients with diagnosis of ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) between 2010 and 2015 were included. We assessed the impact of diabetes mellitus on 30-day and one-year mortality in patients aged less than and at least 75 years. RESULTS: A total of 12 792 cases were registered, of whom 3023 (23.6%) were aged at least 75 years. About 20% patients had previous diabetes mellitus diagnosis. Patients aged at least 75 years had higher prevalence of comorbidities, higher proportion of heart failure at admission, a more extensive coronary artery disease and significant delay to reperfusion (P < 0.001). Diabetes mellitus was associated with higher 30-day mortality both in young [odds ratio (OR) 1.97, 95% confidence interval (CI): 1.43-2.70] and in elderly patients (OR 1.43, 95% CI: 1.07-1.91). After adjusting for potential confounders, this association remained significant in young patients (OR 1.47, 95% CI: 1.00-2.16, P = 0.047), but not in the elderly (OR 1.14, P = 0.43). Likewise, a crude association between diabetes mellitus and one-year mortality was observed in both groups (young patients: HR = 1.93; 95% CI: 1.51-2.46; older patients: HR = 1.33; 95% CI: 1.08-1.64). However, after adjusting for potential confounders, this association remained significant in younger patients (HR = 1.46; 95% CI: 1.13-1.89; P < 0.001), but not in the elderly (HR = 1.16; P = 0.17). CONCLUSION: A significant proportion of these nonselected patients with STEMI had previous diabetes mellitus. The association between diabetes mellitus and outcomes is different according to age.

An eight-gene blood expression profile predicts the response to infliximab in rheumatoid arthritis.

BACKGROUND: TNF alpha blockade agents like infliximab are actually the treatment of choice for those rheumatoid arthritis (RA) patients who fail standard therapy. However, a considerable percentage of anti-TNF alpha treated patients do not show a significant clinical response. Given that new therapies for treatment of RA have been recently approved, there is a pressing need to find a system that reliably predicts treatment response. We hypothesized that the analysis of whole blood gene expression profiles of RA patients could be used to build a robust predictor to infliximab therapy. METHODS AND FINDINGS: We performed microarray gene expression analysis on whole blood RNA samples from RA patients starting infliximab therapy (n = 44). The clinical response to infliximab was determined at week 14 using the EULAR criteria. Blood cell populations were determined using flow cytometry at baseline, week 2 and week 14 of treatment. Using complete cross-validation and repeated random sampling we identified a robust 8-gene predictor model (96.6% Leave One Out prediction accuracy, P = 0.0001). Applying this model to an independent validation set of RA patients, we estimated an 85.7% prediction accuracy (75-100%, 95% CI). In parallel, we also observed a significantly higher number of CD4+CD25+ cells (i.e. regulatory T cells) in the responder group compared to the non responder group at baseline (P = 0.0009). CONCLUSIONS: The present 8-gene model obtained from whole blood expression efficiently predicts response to infliximab in RA patients. The application of the present system in the clinical setting could assist the clinician in the selection of the optimal treatment strategy in RA.

Ëxido nítrico, función endotelial y trastorno depresivo mayor / Nitric oxide, endothelial function and mayor depressive disorder

El trastorno depresivo mayor en una de las enfermedades mentales más prevalentes en el mundo. Por otro lado, las enfermedades cardiovasculares son la primera causa de mortalidad en Colombia, y observaciones epidemiológicas han permitido plantear que la depresión y las enfermedades cardiovasculares tienen una relación bidireccional. El endotelio mantiene el tono vascular, inhibe el crecimiento excesivo del músculo liso, inhibe la adhesión y migración de células blancas y tiene un efecto antiadhesivo plaquetario por medio de la producción de óxido nítrico. De esta manera, niveles disminuidos de óxido nítrico están directamente asociados a disfunción endotelial y por ende a riesgo cardiovascular. Ademßs, es bien conocido que este gas tiene efectos sobre los neurotransmisores monoaminÚrgicos implicados en enfermedades neuropsiquiátricas. Existen estudios que encuentran una asociación entre niveles disminuidos de óxido nítrico en pacientes deprimidos, lo que sugiere que existe un mecanismo fisiopatológico común entre las enfermedades cardiovasculares y los trastornosdepresivos. En el presente artículo revisamos las evidencias que soportan la propuesta de que una alteración de la vía L-arginina-NO a nivel endotelial y neuronal, es el mecanismo fisiopatológico común entre las enfermedades cardiovasculares y los trastornos depresivos.

[Analysis with the propensity score of the association between likelihood of treatment and event of interest in observational studies. An example with myocardial reperfusion]. / Análisis de la asociación entre un tratamiento y un acontecimiento de interés en estudios observacionales utilizando la probabilidad de recibir el tratamiento (Propensity Score). Un ejemplo con la reperfusión miocárdica.

INTRODUCTION AND OBJECTIVES: Analysis of the effect of treatment in observational studies is complex due to differences between treated and nontreated patients. Calculating the probability of receiving treatment conditioned on relevant covariates (propensity score [PS]) has been proposed as a method to control for these differences. We report an application of PS to assess the association between reperfusion treatment and 28-day case fatality in patients with acute myocardial infarction (AMI). METHOD: We describe the procedure used to calculate PS for receiving reperfusion treatment, and different strategies to analyze the association between PS and case fatality with regression modeling and matching. Data were from a population-based registry of 6307 patients with AMI in Spain during 1997-98. RESULTS: The PS for reperfusion was calculated in 5622 patients. In the multivariate analysis, reperfusion was associated with lower case fatality (OR = 0.59; 95% confidence interval [95% CI]: 0.46-0.77). When PS was included as a covariate, this association became non- significant (OR = 0.76; 95% CI: 0.57-1.01). In the subgroup of matched patients with a similar PS (n = 3138), treatment was not associated with case fatality (OR = 0.95; 95% CI: 0.72-1.26). When the influence of cases with missing data on PS was controlled for, reperfusion treatment was associated with lower fatality (OR = 0.66; 95% CI: 0.55-0.80). CONCLUSIONS: Calculating propensity score is a method that controls for differences between treated and nontreated patients. This score has limitations when matching is incomplete and when data are missing. Results of the present example suggest that reperfusion treatment reduces AMI case fatality.

Análisis de la asociación entre un tratamiento y un acontecimiento de interés en estudios observacionales utilizando la probabilidad de recibir el tratamiento (Propensity Score). Un ejemplo con la reperfusión miocárdica / Analysis with the propensity score of the association between likelihood of treatment and event of interest in observational studies. An example with myocardial reperfusion

Introducción y objetivos. Determinar el efecto de un tratamiento en estudios observacionales es problemático por las diferencias existentes entre tratados y no tratados. Un método propuesto para controlar estas diferenciases calcular la probabilidad condicionada por covariables de recibir el tratamiento, Propensity Score (PS).Presentamos una aplicación de este método analizándola asociación entre reperfusión y letalidad a 28 días en pacientes con infarto agudo de miocardio (IAM).Método. Se presenta cómo calcular la PS de recibir reperfusión y las diferentes estrategias para analizar posteriormente su asociación con la letalidad mediante modelos de regresión y apareamiento. Utilizamos datos de un registro poblacional de IAM realizado en España entre1997 y 1998 que incluyó 6.307 IAM. Resultados. Se calculó la PS de reperfusión en 5.622pacientes. En el análisis multivariado la reperfusión se asoció con menor letalidad (odds ratio [OR] = 0,59; intervalo de confianza [IC] del 95%, 0,46-0,77); al ajustara demás por la PS de reperfusión esta asociación no fue significativa (OR = 0,76; IC del 95%, 0,57-1,01). En el subgrupo de pacientes apareados, tratados y no tratados con PS de reperfusión similar (n = 3.138), este tratamiento no se asoció con letalidad (OR = 0,95; IC del95%, 0,72-1,26). Controlando el impacto de los casos con datos insuficientes en la PS de reperfusión, ésta se asoció con menor letalidad (OR = 0,66; IC del 95%,0,55-0,80).Conclusiones. El cálculo de la PS es un método para controlar las diferencias entre los grupos tratado y no tratado. Tiene limitaciones cuando el apareamiento es incompleto o hay datos insuficientes en la PS calculada. Los resultados del ejemplo presentado indican que la reperfusión reduce la letalidad del IAM

Introduction and objectives. Analysis of the effect of treatment in observational studies is complex due to differences between treated and non-treated patients. Calculating the probability of receiving treatment conditioned on relevant covariates (propensity score [PS]) has been proposed as a method to control for these differences. Were port an application of PS to assess the association between reperfusion treatment and 28-day case fatality in patients with acute myocardial infarction (AMI).Method. We describe the procedure used to calculate PS for receiving reperfusion treatment, and different strategies to analyze the association between PS and case fatality with regression modeling and matching. Data were from a population-based registry of 6307 patients with AMI in Spain during 1997-98.Results. The PS for reperfusion was calculated in 5622patients. In the multivariate analysis, reperfusion was associated with lower case fatality (OR = 0.59; 95% confidence interval [95% CI]: 0.46-0.77). When PS was included as a covariate, this association became non-significant (OR = 0.76; 95% CI: 0.57-1.01). In the subgroup of matched patients with a similar PS (n = 3138),treatment was not associated with case fatality (OR =0.95; 95% CI: 0.72-1.26). When the influence of cases with missing data on PS was controlled for, reperfusion treatment was associated with lower fatality (OR = 0.66;95% CI: 0.55-0.80).Conclusions. Calculating propensity score is a method that controls for differences between treated and non-treated patients. This score has limitations when matching is incomplete and when data are missing. Results of the present example suggest that reperfusion treatment reduces AMI case fatality

Dengue virus: detection and pathogeny

Sequences from a cDNA of dengue virus type 4 were cloned into transcription vectors. These sequences included the E, NS1, NS2A, NS2B, NS3 genes. RNA transcipts produced in vitro from these plasmids were used in hybridization assays to detect dengue viral sequences. With these RNA-probes we have been able to detect molecules of serotype-specific dengue 4 viral RNA. Moreover, the riboprobes detected viral sequences of other serotypes in the following order of sensitivity 4 > 2 > 3 > 1, and might be useful to differentiate serotypes