Beneath the surface: Amino acid variation underlying two decades of dengue virus antigenic dynamics in Bangkok, Thailand.

Neutralizing antibodies are important correlates of protection against dengue. Yet, determinants of variation in neutralization across strains within the four dengue virus serotypes (DENV1-4) is imperfectly understood. Studies focus on structural DENV proteins, especially the envelope (E), the primary target of anti-DENV antibodies. Although changes in immune recognition (antigenicity) are often attributed to variation in epitope residues, viral processes influencing conformation and epitope accessibility also affect neutralizability, suggesting possible modulating roles of nonstructural proteins. We estimated effects of residue changes in all 10 DENV proteins on antigenic distances between 348 DENV collected from individuals living in Bangkok, Thailand (1994-2014). Antigenic distances were derived from response of each virus to a panel of twenty non-human primate antisera. Across 100 estimations, excluding 10% of virus pairs each time, 77 of 295 positions with residue variability in E consistently conferred antigenic effects; 52 were within ±3 sites of known binding sites of neutralizing human monoclonal antibodies, exceeding expectations from random assignments of effects to sites (p = 0.037). Effects were also identified for 16 sites on the stem/anchor of E which were only recently shown to become exposed under physiological conditions. For all proteins, except nonstructural protein 2A (NS2A), root-mean-squared-error (RMSE) in predicting distances between pairs held out in each estimation did not outperform sequences of equal length derived from all proteins or E, suggesting that antigenic signals present were likely through linkage with E. Adjusted for E, we identified 62/219 sites embedding the excess signals in NS2A. Concatenating these sites to E additionally explained 3.4% to 4.0% of observed variance in antigenic distances compared to E alone (50.5% to 50.8%); RMSE outperformed concatenating E with sites from any protein of the virus (ΔRMSE, 95%IQR: 0.01, 0.05). Our results support examining antigenic determinants beyond the DENV surface.

Design and development of a new pictorial tool to facilitate communication around advance care planning.

BACKGROUND: Advance care planning (ACP) aims to ensure that people with chronic or advanced disease receive medical care that is consistent with their values and preferences. However, professionals may find it challenging to engage these patients in conversations about the end of life. We sought to develop a pictorial tool to facilitate communication around ACP. METHODS: This was a three-phase study. In phase 1, we used the nominal group and Delphi techniques to achieve expert consensus regarding the conceptual content of the tool. In phase 2, a professional cartoonist was commissioned to create a series of cartoons representing each of the content areas resulting from the Delphi process. The pictorial tool was then administered (phase 3) with a sample of individuals with advanced/chronic disease to explore whether the cartoons were easy to understand and conveyed the intended message. RESULTS: Following a three-round Delphi process, consensus was reached regarding a set of 12 key content areas that should be considered in the context of an ACP interview. The cartoons created to represent each of the 12 areas were then reviewed and ordered so as to reflect the typical stages of an end-of-life care interview. After administering the pictorial tool with 24 frail older adults with advanced/chronic disease, changes were made to 9 of the 12 cartoons. CONCLUSIONS: The new pictorial tool comprises a set of 12 cartoons that can guide professionals as they seek to engage frail older adults with advanced/chronic disease in conversations about the end of life and ACP.

Efficacy and Safety of Methadone as a Second-Line Opioid for Cancer Pain in an Outpatient Clinic: A Prospective Open-Label Study.

INTRODUCTION: Most clinical reports on methadone rotation describe outcomes in hospitalized patients. The few studies that have included outpatients are retrospective. The aim of this study was to assess the efficacy and safety of methadone as a second-line opioid in adult patients with advanced cancer after rotation in routine clinical practice at a palliative care outpatient clinic. PATIENTS AND METHODS: This was a prospective, open-label study of 145 patients whose treatment was rotated from other opioids to methadone. Informed consent was obtained in all cases. The main outcome measure was change in the variable "worst pain" at day 28. Pain and pain interference were assessed with the Brief Pain Inventory, with side effects evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Pain levels were evaluated at study entry and at days 3, 7, 9, 14, 21, and 28. RESULTS: Rotation to methadone was performed for the following reasons: poor pain control (77.9%), opioid side effects (2.1%), or both (20%). The mean daily oral morphine equivalent dose before rotation was 193.7 mg. The median worst and average pain scores decreased significantly (p < .0001) from baseline to day 28: The median worst pain score decreased from 9 (interquartile range [IQR]: 8-10) to 6 (IQR: 3-8), and the median average pain score decreased from 6 (IQR: 5-7) to 4 (IQR: 2-5). The proportions of patients with moderate to severe worst and average pain decreased by 30.3% and 47.5%, respectively, by day 28. No increase in opioid toxicity was observed during the study. CONCLUSION: In outpatients with advanced cancer, rotation to methadone as a second-line opioid was efficacious and safe when using a tiered scheme with close follow-up by experienced health professionals. IMPLICATIONS FOR PRACTICE: The results of this study, conducted prospectively under real clinical conditions, support the efficacy and safety of oral methadone as a second-line opioid in ambulatory patients with cancer. Moreover, these findings corroborate previously reported outcomes in retrospective outpatient studies and prospective studies that evaluated inpatient populations. Although more research into methadone rotation strategies is still needed, this study describes a successful tiered scheme of oral methadone rotation that was proven safe and effective during follow-up.

Physical and psychological factors and the wish to hasten death in advanced cancer patients.

BACKGROUND: Qualitative research suggests that the wish to hasten death (WTHD) in the advanced stages of disease is mainly related to overall suffering. This quantitative study explores the relationship between the WTHD and psychological and physical factors, including survival, in patients with advanced cancer. METHODS: Cross-sectional study of 101 advanced cancer patients admitted to an acute Palliative Care Unit (PCU) and followed-up for survival. Patients were assessed using the Schedule of Attitudes toward Hastened Death (SAHD). The Hospital Anxiety and Depression Scale (HADS), Eastern Cooperative Oncology Group Performance Status, and the Barthel Index were used to assess psychological and physical status. Survival prognosis was based on the Palliative Prognostic score. RESULTS: The Spanish adaptation of SAHD showed good psychometric properties (Cronbach's alpha 0.92; similar concurrent/discriminant validity to the original). The mean total score on SAHD was 4.9 (standard deviation [SD] = 5.3). SAHD scores were positively correlated with HADS-Total (r = 0.332, p < 0.01), HADS-Depression (r = 0.397, p < 0.01), Eastern Cooperative Oncology Group Performance Status (r = 0.276, p < 0.01), and Palliative Prognostic score (r = 0.248, p < 0.05) and negatively correlated with the Barthel Index (r = -0.324, p < 0.01). Women scored higher than men on SAHD (6.2, SD = 5.9 vs. 4.2, SD = 4.8, p < 0.01). No association was found between WTHD and survival (r = -0.12, p > 0.05). CONCLUSIONS: Both psychological and physical impairment (as well as poorer prognosis) are associated with higher scores on SAHD, supporting the idea that WTHD emerges in response to overall suffering. Although we observed a direct relationship between physical status and survival, the latter was not related to any of the psychological factors or WTHD.

Left Atrial Peak Systolic Strain as an Indicator Pathway of Diastolic Dysfunction of the Left Ventricle.

BACKGROUND: Left atrial peak systolic strain (LA-PSS) imaging is an emerging index of left atrial function, and it was shown to be decreased in heart failure with preserved ejection fraction (EF). We aimed to determine whether LA-PSS could be used as an additional diagnostic parameter to current existing guidelines for the presence of left ventricle diastolic dysfunction (LVDD). MATERIALS AND METHODS: A total of 190 consecutive adult patients with cardiovascular risk factors and normal left ventricle EF with no prior history of heart failure were included in the study. Speckle tracking software was used to study ventricular parietal deformity, left ventricle global longitudinal systolic strain, and LA-PSS. RESULTS: The median left ventricle global longitudinal systolic strain was -19%, with a significant difference ( P < 0.001) between patients with normal diastolic function versus those with LVDD. The median LA-PSS was 33% (30% to 38%) ( P < 0.001). Most patients (61%) had grade 1 atrial dysfunction based on PSS (range 24%-35%). The analysis of the area under the receiver operating characteristic curve of the LA-PSS as a potential indicator pathway of LVDD was 67% [95% confidence interval (CI), 62-72], and 75% (95% CI, 70-80), when the indeterminate pattern was included. The decreased LA-PSS made it possible to reclassify patients with an indeterminate pattern of diastolic function in 96% of cases. CONCLUSIONS: These results support the potential role of LA-PSS as an additional parameter for the diagnosis of LVDD in patients with normal EF, and may be integrated into the guidelines for routine evaluation of patients.

Role of the Electrocardiographic MVP Risk Score (Morphology-Voltage-P Wave Duration) in Predicting the Development of Atrial Fibrillation in Patients With Systemic Arterial Hypertension.

BACKGROUND: There is a global tendency to emphasize the prevention and early diagnosis of diseases that have a great impact on public health. Atrial fibrillation (AF) has a prevalence affecting 1.5-2% of the general population. Certain variables of the P wave allow us to identify and stratify patients at risk of developing AF. MATERIALS AND METHODS: This is an observational, descriptive, and longitudinal study to determine the applicability of the electrocardiographic (ECG) morphology, voltage, and P wave duration (MVP) risk score to predict the development of AF in consecutive patients with systemic hypertension (SH) in an initial follow-up of 12 months. RESULTS: Initially, 104 patients were included, of whom 12 died during follow-up and 17 did not attend subsequent checkups during the COVID-19 pandemic; therefore, they were excluded. The study patients were 75, of whom AF was detected in 25 patients (33%). The average duration of the P wave was 120 ± 26 ms, the average voltage was 0.1 ± 0.5 Mv. The high-risk MVP ECG score had an [area under the curve, 0.69; 95% confidence intervals (CI), 0.59-0.79] and demonstrated a specificity and a positive predictive value of 100%, a negative predictive value of 76%, and a sensitivity of 40% for predicting the development of AF. CONCLUSIONS: The present study establishes for the first time that SH patients who possess a high-risk MVP ECG score have a significantly higher incidence of developing AF. The high-risk MVP Score has a specificity and a positive predictive value of 100% and a high negative predictive value with a moderate sensitivity for the prediction of the development of AF in SH patients.

Relationship of the T-wave Tpeak-Tend interval with conduction system disorders in arterial hypertension.

PURPOSE: The Tpeak-Tend interval of the T wave has emerged as a new electrocardiographic marker of increased transmural dispersion of ventricular repolarization. We aimed to determine the presence of cardiac conduction system disorders in patients with systemic arterial hypertension (SAH) who have altered Tpeak-Tend interval of the T wave. METHODS: The 67 patients with SAH were divided into two groups. Those with prolonged (≥ 77 ms) Tpeak-Tend intervals, 21 (31%) patients were in the study group. Those with normal (< 77 ms) Tpeak-Tend intervals, 46 (69%) patients were in the control group. Alteration of ventricular repolarization manifested as a prolongation of the Tpeak-Tend interval was detected by computerized electrocardiographic analysis tools. RESULTS: The median value of QRS complex duration was significantly wider in the study group as compared to the control group (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). There was a significantly greater incidence of left anterior hemiblock in the study group (14% vs. 0% p < 0.04). The median value of the QTc interval was significantly greater in the study group (440 ± 26 vs. 422 ± 15 p < 0.01). There was a significantly greater incidence of patients with prolonged QTc interval in the study group (33% vs. 11% p < 0.02). The median value of the Tpeak-Tend interval was significantly greater in the study group (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), as well as, the Tpeak-Tend/QTc ratio in the study group (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). CONCLUSION: There is a significantly greater ventricular repolarization disorders and abnormalities of the cardiac conduction system in SAH patients who possess altered Tpeak-Tend interval of the T wave.

OBJETIVO: El intervalo Tpico-Tfinal de la onda T es un marcador electrocardiográfico de la dispersión transmural aumentada de la repolarización ventricular. Investigamos la presencia de trastornos del sistema de conducción cardíaca en pacientes con hipertensión arterial sistémica (HA) que poseen alterado el intervalo Tpico-Tfinal de la onda T. MÉTODOS: Los 67 pacientes con HA fueron divididos en dos grupos. Aquellos con intervalos de Tpico-Tfinal prolongados (≥ 77 ms), 21 (31%) pacientes (grupo de estudio). Aquellos con intervalos normales (< 77 ms) Tpico-Tfinal, 46 (69%) pacientes (grupo control). Los intervalos Tpico-Tfinal fueron medidos por herramientas de análisis electrocardiográfico computarizado. RESULTADOS: El valor mediano de la duración del complejo QRS fue significativamente más amplio en el grupo de estudio (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). Hubo una incidencia significativamente mayor de hemibloqueo anterior izquierdo en el grupo de estudio (14% vs. 0% p < 0.04). El valor mediano del intervalo QTc fue significativamente mayor en el grupo de estudio (440 ± 26 vs. 422 ± 15 p < 0.01). Hubo una incidencia significativamente mayor de pacientes con intervalo QTc prolongado en el grupo de estudio (33% vs. 11% p < 0.02). El valor mediano del intervalo Tpico-Tfinal fue significativamente mayor en el grupo de estudio (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), así como el cociente Tpico-Tfinal/QTc (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). CONCLUSIÓN: Existe una alteración de la repolarización ventricular significativamente mayor y anomalías del sistema de conducción cardíaca en pacientes con HA que poseen alteración del intervalo Tpico-Tfinal de la onda T.

The wish to hasten death: a review of clinical studies.

It is common for patients who are faced with physical or psychological suffering, particularly those in the advanced stages of a disease, to have some kind of wish to hasten death (WTHD). This paper reviews and summarises the current state of knowledge about the WTHD among people with end-stage disease, doing so from a clinical perspective and on the basis of published clinical research. Studies were identified through a search strategy applied to the main scientific databases. Clinical studies show that the WTHD has a multi-factor aetiology. The literature review suggests-perhaps in line with better management of physical pain-that psychological and spiritual aspects, including social factors, are the most important cause of such a wish. One of the difficulties facing clinical research is the lack of terminological and conceptual precision in defining the construct. Indeed, studies frequently blur the distinction between a generic wish to die, a WTDH (whether sporadic or persistent over time), the explicit expression of a wish to die, and a request for euthanasia or physician-assisted suicide. A notable contribution to knowledge in this field has been made by scales designed to evaluate the WTHD, although the problems of conceptual definition may once again limit the conclusions, which can be drawn from the results. Studies using qualitative methodology have also provided new information that can help in understanding such wishes. Further clinical research is needed to provide a complete understanding of this phenomenon and to foster the development of suitable care plans.

Psychometric properties of the Spanish form of the Schedule for Meaning in Life Evaluation (SMiLE).

OBJECTIVE: The objective of this study was to validate the Spanish version of the SMiLE (Schedule for Meaning in Life Evaluation). The SMiLE is a respondent-generated instrument: respondents are first asked to list three to seven areas, which provide meaning to their lives, and then to rate their current satisfaction with the listed areas, as well as the individual importance of each one. Indices of total weighting (IoW), total satisfaction (IoS), and total weighted satisfaction (IoWS) are calculated. METHODS: Two hundred and fifty University students responded to the Spanish version of the SMiLE, as well as to instruments for measuring self-esteem, quality of life, depression, and anxiety. RESULTS: The Cronbach alphas (α = 0.61 for IoS and α = 0.41 for IoW) and test-retest correlations were comparable to those found in the initial validation of the instrument (IoS: r = 0.55; IoW: r = 0.61). The SMiLE showed positive correlations with self-esteem (r = 0.28, P < 0.05 for IoS) and the mental dimension of the quality of life scale (r = 0.31, P < 0.05 for IoS), while negative correlations were observed with depression (r = -0.23, P < 0.01) and anxiety (r = -0.17, P < 0.05). CONCLUSIONS: The results support the validity of the Spanish version of the SMiLE as an instrument for assessing meaning in life.

The relation between QRS complex fragmentation and segmental abnormalities of the myocardial contractility in patients with coronary artery disease.

BACKGROUND: Fragmented QRS (fQRS) is defined as any QRS complex with duration of less than 120 ms (ms) and at least one notch in the R or S wave in two or more leads belonging to the same coronary territory. The fQRS represents a delay in ventricular conduction caused by a myocardial scar associated to arrhythmic events. METHODS: This is a descriptive, retrospective, cross-sectional study of a total of 123 patientsadmitted with ischemic heart disease. The aim was to correlate the presence of fQRS in a conventional 12-leads electrocardiogram (ECG) with myocardial regional motility disorders. RESULTS: A total of 62% of the patients were male, the mean age was 63 ± 12 SD. fQRS was observed in 44% (64% men and 36% women), the most frequent location being the inferior wall (61%), followed by the anteroseptal and lateral walls (14% for both). Of the 36 patients with fQRS, 30 had segmental disorders, while 6 did not. Of the 45 patients without fQRS, 28 had segmental disorders, but 17 did not, which gives us a sensitivity of 52% (moderate SnNout) and specificity of 74% (high SpPin), with a positive predictive value of 83%, a negative predictive value of 38% and a prevalence of 72%. CONCLUSION: The presence of fQRS in the ECG has high specificity and a high positive predictive value of the existence of segmental myocardial motility disorders in patients with documented coronary artery disease.

[Orthostatic and postprandial hypotension in elderly patients with chronic diseases and disability: prevalence and related factors]. / Hipotensión ortostática e hipotensión posprandial en pacientes ancianos con discapacidad y enfermedades crónicas: prevalencia y factores relacionados.

INTRODUCTION: To assess the prevalence of orthostatic hypotension (OH) and postprandial hypotension (PPH) in patients admitted to an intermediate care unit, as well as to analyze the characteristics of these patients. PATIENTS AND METHODS: Sixty patients were analyzed according to the following criteria: age >65 years, able to take food orally, stand up and/or sit down, and clinically stable. A comprehensive geriatric assessment was carried out and the main diagnosis and the presence of autonomic neuropathy symptoms (ANS) were registered. Blood pressure (BP) was registered in the morning in supine position during the first 3min of postural change (standing or sitting). OH was defined as a decrease in systolic blood pressure (SBP) of 20mm Hg or a decrease in diastolic blood pressure (DBP) of 10mmHg. BP was registered after 15min of sitting and 60min after breakfast. PPH was defined as a decrease in SBP of 20mmHg. RESULTS: The mean age was 79.1+/-7.8 years. Nine patients (15%) had OH and 29 (48.3%) had PPH. The mean Lawton index (LI) score in patients with OH was 3.1+/-2.1 and was 5.2+/-2.6 in the remaining patients (P<.02). The mean body mass index (BMI) was 23.3+/-3.1 vs. 26.2+/-5.1 (P<.04). ANS was present in all nine patients (100%) with OH but in only 30 (58.8%) of the remaining 51 patients (chi-square=5.71; P<.03). CONCLUSIONS: PPH was more frequent than OH. Patients with OH had a significantly lower LI score and BMI. The presence of ANS was significantly more frequent in patients with OH. There was no significant relationship between HO and PPH or among the remaining variables studied.

Factores asociados a la calidad de vida en adultos mayores con insuficiencia orgánica crónica avanzada en un hospital de Lima-Perú

Objetivo: Determinar los factores asociados a la calidad de vida en adultos mayores con insuficiencia orgánica crónica avanzada en un hospital de Lima-Perú. Materiales y métodos: Investigación observacional, analítica transversal, cuya población la conformaron 100 adultos mayores, la técnica de recolección fue la entrevista y el instrumento el cuestionario a través de la aplicación del índice de Barthel y WHOQoL-Bref. Para responder a los objetivos de estudio se aplicaron las pruebas no paramétricas u de Mann Whitney, Kruskal Wallis y Rho de Spearman, considerando la significancia del 5%. Resultados: El (44) 44% de adultos mayores tuvieron más de 80 años, el (59) 59% fueron varones, el (31) 31% estudiaron nivel técnico superior, el (57) 57% fueron titulares en la marina de guerra, el (74) 74% tuvo hipertensión arterial. Los síndromes geriátricos más frecuentes fueron déficit visual o auditivo (82) 82%, insomnio (59) 59%, estreñimiento (52) 52% y malnutrición (47) 47%. El (50) 50% de los adultos mayores presentó dependencia funcional grave. El (63)63% presentó calidad de vida a nivel medio. Los factores epidemiológicos asociados a la baja calidad de vida, fueron la edad mayor a 80 años (p=0,032, RP=1,818), sexo femenino (p=0,009, RP=2,056), el grado de instrucción dado por analfabeto, primaria y secundaria (p=0,025, RP=1,930) y la relación con la marina de guerra como familiar (p=0,022, RP=1,894). Los síndromes geriátricos asociados fueron el insomnio (p=0,034, RP=1,930), el estreñimiento (p=0,000, RP=3,560), la lesión por presión (p=0,000, RP=2,788) y la dependencia funcional grave (p=0,000, RP=4,667). Sin embargo, el análisis multivariado evidenció que el insomnio (p=0,002; RPa=1,166), la lesión por presión (p=0,016; RPa=1,248) y la dependencia grave (p=0,000; RPa=1,207) fueron los factores asociados significativamente a la baja calidad de vida en los adultos mayores. Conclusiones: Los factores insomnio, la lesión por presión y la dependencia grave estuvieron asociados significativamente a la calidad de vida baja en los adultos mayores con insuficiencia orgánica crónica avanzada en un hospital de lima-Perú.

Objective: To determine the factors associated with the quality of life in older adults with advanced chronic organ failure in a hospital in Lima-Peru. Materials and methods: Observational research, cross-sectional analysis, whose population was made up of 100 older adults, the collection technique was the interview and the instrument the questionnaire through the application of the Barthel index and WHOQoL-Bref. To respond to the study objectives, the non-parametric Mann Whitney u, Kruskal Wallis and Spearman's Rho tests were applied, considering the significance of 5%. Results: (44) 44% of older adults were over 80 years old, (59) 59% were men, (31) 31% studied a higher technical level, (57) 57% were incumbents in the navy, (74) 74% had arterial hypertension. The most frequent geriatric syndromes were visual or auditory deficit (82) 82%, insomnia (59) 59%, constipation (52) 52% and malnutrition (47) 47%. The (50) 50% of the older adults presented severe functional dependence. (63) 63% presented quality of life at a medium level. The epidemiological factors associated with low quality of life were age over 80 years (p=0.032, RP=1.818), female sex (p=0.009, RP=2.056), the level of education given by illiterate, primary and secondary school (p=0.025, RP=1.930) and the relationship with the navy as a family member (p=0.022, RP=1.894). Associated geriatric syndromes were insomnia (p=0.034, RP=1.930), constipation (p=0.000, RP=3.560), pressure injury (p=0.000, RP=2.788) and severe functional dependence (p= 0.000, PR=4.667). However, the multivariate analysis showed that insomnia (p=0.002; RPa=1.166), pressure injury (p=0.016; RPa=1.248) and severe dependence (p=0.000; RPa=1.207) were the associated factors. Significantly to the low quality of life in older adults. Conclusions: The factors insomnia, pressure injury and severe dependency were significantly associated with low quality of life in older adults with advanced chronic organ failure in a hospital in Lima-Peru.

Viridot: An automated virus plaque (immunofocus) counter for the measurement of serological neutralizing responses with application to dengue virus.

The gold-standard method for quantifying neutralizing antibody responses to many viruses, including dengue virus (DENV), is the plaque reduction neutralization test (PRNT, also called the immunofocus reduction neutralization test). The PRNT conducted on 96-well plates is high-throughput and requires a smaller volume of antiserum than on 6- or 24-well plates, but manual plaque counting is challenging and existing automated plaque counters are expensive or difficult to optimize. We have developed Viridot (Viridot package), a program for R with a user interface in shiny, that counts viral plaques of a variety of phenotypes, estimates neutralizing antibody titers, and performs other calculations of use to virologists. The Viridot plaque counter includes an automatic parameter identification mode (misses <10 plaques/well for 87% of diverse DENV strains [n = 1521]) and a mode that allows the user to fine-tune the parameters used for counting plaques. We compared standardized manual and Viridot plaque counting methods applied to the same wells by two analyses and found that Viridot plaque counts were as similar to the same analyst's manual count (Lin's concordance correlation coefficient, ρc = 0.99 [95% confidence interval: 0.99-1.00]) as manual counts between analysts (ρc = 0.99 [95% CI: 0.98-0.99]). The average ratio of neutralizing antibody titers based on manual counted plaques to Viridot counted plaques was 1.05 (95% CI: 0.98-1.14), similar to the average ratio of antibody titers based on manual plaque counts by the two analysts (1.06 [95% CI: 0.84-1.34]). Across diverse DENV and ZIKV strains (n = 14), manual and Viridot plaque counts were mostly consistent (range of ρc = 0.74 to 1.00) and the average ratio of antibody titers based on manual and Viridot counted plaques was close to 1 (0.94 [0.86-1.02]). Thus, Viridot can be used for plaque counting and neutralizing antibody titer estimation of diverse DENV strains and potentially other viruses on 96-well plates as well as for formalization of plaque-counting rules for standardization across experiments and analysts.

Relationship of the T-wave Tpeak-Tend interval with conduction system disorders in arterial hypertension / Relación del intervalo Tpico-Tfinal de la onda T con trastornos del sistema de conducción en hipertensión arterial

Abstract Purpose: The Tpeak-Tend interval of the T wave has emerged as a new electrocardiographic marker of increased transmural dispersion of ventricular repolarization. We aimed to determine the presence of cardiac conduction system disorders in patients with systemic arterial hypertension (SAH) who have altered Tpeak-Tend interval of the T wave. Methods: The 67 patients with SAH were divided into two groups. Those with prolonged (≥ 77 ms) Tpeak-Tend intervals, 21 (31%) patients were in the study group. Those with normal (< 77 ms) Tpeak-Tend intervals, 46 (69%) patients were in the control group. Alteration of ventricular repolarization manifested as a prolongation of the Tpeak-Tend interval was detected by computerized electrocardiographic analysis tools. Results: The median value of QRS complex duration was significantly wider in the study group as compared to the control group (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). There was a significantly greater incidence of left anterior hemiblock in the study group (14% vs. 0% p < 0.04). The median value of the QTc interval was significantly greater in the study group (440 ± 26 vs. 422 ± 15 p < 0.01). There was a significantly greater incidence of patients with prolonged QTc interval in the study group (33% vs. 11% p < 0.02). The median value of the Tpeak-Tend interval was significantly greater in the study group (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), as well as, the Tpeak-Tend/QTc ratio in the study group (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). Conclusion: There is a significantly greater ventricular repolarization disorders and abnormalities of the cardiac conduction system in SAH patients who possess altered Tpeak-Tend interval of the T wave.

Resumen Objetivo: El intervalo Tpico-Tfinal de la onda T es un marcador electrocardiográfico de la dispersión transmural aumentada de la repolarización ventricular. Investigamos la presencia de trastornos del sistema de conducción cardíaca en pacientes con hipertensión arterial sistémica (HA) que poseen alterado el intervalo Tpico-Tfinal de la onda T. Métodos: Los 67 pacientes con HA fueron divididos en dos grupos. Aquellos con intervalos de Tpico-Tfinal prolongados (≥ 77 ms), 21 (31%) pacientes (grupo de estudio). Aquellos con intervalos normales (< 77 ms) Tpico-Tfinal, 46 (69%) pacientes (grupo control). Los intervalos Tpico-Tfinal fueron medidos por herramientas de análisis electrocardiográfico computarizado. Resultados: El valor mediano de la duración del complejo QRS fue significativamente más amplio en el grupo de estudio (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). Hubo una incidencia significativamente mayor de hemibloqueo anterior izquierdo en el grupo de estudio (14% vs. 0% p < 0.04). El valor mediano del intervalo QTc fue significativamente mayor en el grupo de estudio (440 ± 26 vs. 422 ± 15 p < 0.01). Hubo una incidencia significativamente mayor de pacientes con intervalo QTc prolongado en el grupo de estudio (33% vs. 11% p < 0.02). El valor mediano del intervalo Tpico-Tfinal fue significativamente mayor en el grupo de estudio (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), así como el cociente Tpico-Tfinal/QTc (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). Conclusión: Existe una alteración de la repolarización ventricular significativamente mayor y anomalías del sistema de conducción cardíaca en pacientes con HA que poseen alteración del intervalo Tpico-Tfinal de la onda T.

Correction: An International Consensus Definition of the Wish to Hasten Death and Its Related Factors.

[This corrects the article DOI: 10.1371/journal.pone.0146184.].

Multivessel coronary thrombosis and acute myocardial infarction associated to two genetic mutations for thrombophilia / Trombosis coronaria de múltiples vasos e infarto agudo de miocardio asociado a dos mutaciones genéticas para trombofilia

Abstract Several studies suggest that gene mutations from thrombophilia may constitute a significant risk factor for coronary artery disease, especially in young patients with normal coronaries and non-significant lesions. It is presented a case of a 42-year-old male patient who arrived at the emergency room due to an acute myocardial infarction. The electrocardiogram showed an ST elevation with upward convexity of 4 mm from V1 to V4 and of 1 mm at V5 and V6. Cardiac enzymes were positive (troponin I 8.4 ng/dl, normal range < 1 ng/dl). It was found septum and apical hypokinesia, with an ejection fraction of 44%. The culprit lesion of the infarction was treated with primary angioplasty, successfully dilating the left anterior descending coronary artery. However, spontaneous thrombi appeared at the middle third of the circumflex artery, an area without occlusive lesions previously. A full laboratory assessment for prothrombotic state diseases revealed positivity for gene mutations at A1298C from the methylene tetrahydropholate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1). Gene mutations at A1298C from the MTHFR and PAI-1 should be considered in young patients with acute coronary syndrome, mainly when thrombi are found in non-culprit arteries with no or non-significant coronary lesions.

Resumen Las mutaciones genéticas de la trombofilia pueden constituir un factor de riesgo significativo para la enfermedad de la arteria coronaria, especialmente en pacientes jóvenes con arterias coronarias normales y lesiones no significativas. Se presenta el caso de un paciente masculino de 42 años con infarto agudo de miocardio. El electrocardiograma demostró una elevación del ST con convexidad ascendente de 4 mm de V1 a V4 y de 1 mm en V5 y V6. Las enzimas cardíacas fueron positivas (troponina I 8.4 ng/dl, rango normal < 1 ng/dl). Se observó hipocinesia septal y apical con fracción de eyección de 44%. La lesión causante del infarto fue tratada con angioplastia primaria, dilatando con éxito la arteria coronaria descendente anterior. Sin embargo, aparecieron trombos espontáneos en el tercio medio de la arteria circunfleja, que previamente no presentaba lesiones ateroscleróticas oclusivas. Al evaluar enfermedades protrombóticas se reveló positividad para mutaciones del gen A1298C de la metileno tetrahidrofolato reductasa (MTHFR) y del inhibidor del activador del plasminógeno (PAI-1) del genotipo heterocigoto 675G. Las mutaciones en A1298C del gen MTHFR y del PAI-1 deben considerarse en jóvenes con síndrome coronario agudo, principalmente cuando se encuentran trombos en arterias no culpables sin lesiones coronarias significativas.

Rol de la morfología y dispersión de la onda P en la predicción de fibrilación auricular

RESUMEN Las características anisotrópicas ocasionadas por un miocardio auricular patológico pueden jugar un papel importante en la creación de circuitos de reentrada al causar propagación no homogénea y discontinua del impulso en el miocardio auricular. Este miocardio auricular alterado puede generar bloqueo unidireccional, retraso de la conducción y ritmos auriculares reentrantes. En estas condiciones la onda P del electrocardiograma (ECG) puede mostrar alteraciones que pueden asociarse con arritmias auriculares y fibrilación auricular (FA). La dispersión de la onda P (DP) se considera un marcador no invasivo del ECG para el remodelado auricular y es predictor sensible y específico del desarrollo de FA. Se ha demostrado que el aumento de la duración de la onda P y la DP reflejan la prolongación del tiempo de conducción auricular dentro de la aurícula derecha y entre ambas aurículas, y una propagación auricular no homogénea y discontinua de los impulsos sinusales. Un valor de corte de 40 ms de la DP demostró tener una sensibilidad del 83%, una especificidad del 85% y un valor predictivo positivo del 89% para la identificación de pacientes con antecedentes de FA paroxística aislada. Los pacientes con alteración de la morfología de la onda P y dispersión de la onda P en el ECG tienen una gran susceptibilidad a desarrollar FA porque poseen electrogramas endocárdicos auriculares anormalmente prolongados y fraccionados, una duración de onda P significativamente mayor, un tiempo de conducción intraauricular e interauricular significativamente más largo, y una mayor incidencia de inducción de fibrilación auricular sostenida.

ABSTRACT The anisotropic characteristics caused by a pathological atrial myocardium can play an important role in the creation of reentry circuits by causing discontinuous and inhomogeneous impulse propagation in the atrial myocardium. This altered atrial myocardium can lead to unidirectional block, conduction delay, and reentrant atrial rhythms. Under these conditions, the P wave of the electrocardiogram (ECG) can demonstrate alterations that can be associated with atrial arrhythmias and atrial fibrillation (AF). The P-wave dispersion (PD) is considered a non-invasive ECG marker for atrial remodeling and is a sensitive and specific predictor of the development of AF. Increased P wave duration and PD have been shown to reflect prolonged atrial conduction time within the right atrium and between both atria, and discontinuous, inhomogeneous atrial propagation of sinus impulses. A cutoff value of 40 ms for PD was shown to have a sensitivity of 83%, a specificity of 85%, and a positive predictive value of 89% for the identification of patients with a history of isolated paroxysmal AF. Patients with abnormal P wave morphology and P wave dispersion on the ECG are highly susceptible to developing AF because they have abnormally prolonged and fractionated atrial endocardial electrograms, significantly longer P wave duration, and significantly longer intra-atrial and inter-atrial conduction time, and a higher incidence of sustained atrial fibrillation induction.

An International Consensus Definition of the Wish to Hasten Death and Its Related Factors.

BACKGROUND: The desire for hastened death or wish to hasten death (WTHD) that is experienced by some patients with advanced illness is a complex phenomenon for which no widely accepted definition exists. This lack of a common conceptualization hinders understanding and cooperation between clinicians and researchers. The aim of this study was to develop an internationally agreed definition of the WTHD. METHODS: Following an exhaustive literature review, a modified nominal group process and an international, modified Delphi process were carried out. The nominal group served to produce a preliminary definition that was then subjected to a Delphi process in which 24 experts from 19 institutions from Europe, Canada and the USA participated. Delphi responses and comments were analysed using a pre-established strategy. FINDINGS: All 24 experts completed the three rounds of the Delphi process, and all the proposed statements achieved at least 79% agreement. Key concepts in the final definition include the WTHD as a reaction to suffering, the fact that such a wish is not always expressed spontaneously, and the need to distinguish the WTHD from the acceptance of impending death or from a wish to die naturally, although preferably soon. The proposed definition also makes reference to possible factors related to the WTHD. CONCLUSIONS: This international consensus definition of the WTHD should make it easier for clinicians and researchers to share their knowledge. This would foster an improved understanding of the phenomenon and help in developing strategies for early therapeutic intervention.

What Gives Meaning in Life to Patients With Advanced Cancer? A Comparison Between Spanish, German, and Swiss Patients.

CONTEXT: Meaning in life (MiL) is a construct that varies across individuals, situations, cultures, and countries, and protects against emotional distress at the end of life. OBJECTIVES: To examine MiL in inpatients with advanced cancer from Barcelona, Spain, and to compare the findings with those obtained in German and Swiss samples. METHODS: This was a cross-sectional study in which the Schedule for Meaning in Life Evaluation (SMiLE) was administered. The SMiLE asks respondents to list individual areas that give meaning in their lives and then to rate their current level of importance and satisfaction with the listed areas. RESULTS: A total of 101 inpatients completed the SMiLE. The Index of Satisfaction was 76.8 ± 21.1, the Index of Weighting was 88.0 ± 13.0, and the Index of Weighted Satisfaction was 76.9 ± 20.7. Family, partnership, well-being, and friends were the four areas listed by the largest proportion of Spanish patients. Compared with the German sample, Spanish patients were more likely to list well-being (P < 0.01) and pleasure (P < 0.05) and less likely to list animals/nature, leisure time, and finances (P < 0.01). With respect to their Swiss counterparts, Spanish patients were more likely to list health (P < 0.01) and less likely to list friends, leisure time, animals/nature, and finances (P < 0.01). CONCLUSION: Differences were identified in the areas of MiL listed by the participants according to country of origin. Compared with their German and Swiss counterparts, the Spanish patients listed more areas involving interpersonal relationships. Interpersonal relationships, at both the family and wider social level, are reported to be the areas that give the greatest MiL to these patients. These aspects, therefore, should be considered when drawing up care plans designed to help patients achieve the maximum possible comfort and quality of life.