Increased PAI-1 plasma levels and risk of death from dengue: no association with the 4G/5G promoter polymorphism

BACKGROUND: Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue. METHODS: A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis. RESULTS: Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue. CONCLUSION: These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored

Epidemiology of Febrile Diseases in the Emergency Department of a Caribbean Island: The Curaçao Experience

Objective: The aetiology of febrile diseases in tropical countries often remains poorly characterized. We aim to describe the aetiology and outcome of febrile illnesses at the Emergency Department (ED) in Curaçao. Methods: From April 2008 – April 2009, all adult febrile patients (T > 38.5°C) at the ED of the St Elisabeth Hospital, Curaçao, Netherlands Antilles, were included. Clinical data were recorded, routine laboratory measurements and blood cultures were taken. Final diagnoses were made at discharge by an independent physician and in retrospect by the main investigator. Results: Four hundred and three patients were included: 223 patients (55.6%) were hospitalized, 32 patients (7.9%) died and 18 patients (4.5%) were admitted to the Intensive Care Unit. In 129 febrile patients (32.0%), infection was proven; 84.4% of patients had bacterial (29.0% urinary tract infection, 23.2% pneumonia infection), 5.6% viral and 10.0% parasitic or fungal infections. Twenty-one patients (5.2%) were discharged with a non-infectious diagnosis and 172 patients (42.7%) without a clear diagnosis. Conclusion: A high mortality rate of 7.9% was observed. We found a high prevalence of bacterial infections, with pneumonia and urinary tract infections as the most common causes of fever. One in 20 patients did not have an infectious disease. Keywords: Caribbean region, emergency medicine, epidemiology, fever "Epidemiología de las Enfermedades Febriles en el Departamento de Emergencias de una Isla Caribeña: la Experiencia de Curazao" RESUMEN Objetivo: La etiología de las enfermedades febriles en los países tropicales posee aún una pobre caracterización. El presente trabajo se propone describir la etiología y la evolución clínica de las enfermedades febriles en el Departamento de Emergencias (DE) de Curazao. Métodos: De abril 2008 – abril 2009, todos los pacientes febriles adultos (T > 38.5°C) en el DE del Hospital Saint Elisabeth, de Curazao, Antillas Holandesas, fueron incluidos. Se registraron los datos clínicos, se tomaron las medidas de rutina de laboratorio y los cultivos de sangre. Los diagnósticos finales se hicieron a la hora del alta por un médico independiente y en retrospectiva por el investigador principal. Resultados: Se incluyeron cuatrocientos tres pacientes: 223 pacientes (55.6%) fueron hospitalizados, 32 pacientes (7.9%) murieron, y 18 pacientes (4.5%) fueron ingresados en la Unidad de Cuidados Intensivos. En 129 pacientes febriles (32.0%) se comprobó la infección; 84.4% de los pacientes tenían infección bacteriana (29.0% infección de las vías urinarias, 23.2% infección por pneumonia), 5.6% viral y 10.0% infección parasitaria o fúngica. Veintiún pacientes (5.2%) fueron dados de alta con un diagnóstico no infeccioso, y 172 pacientes (42.7%) sin un diagnóstico claro. Conclusión: Se observó una alta tasa de mortalidad de 7.9%. Se halló una alta prevalencia de infecciones bacterianas, siendo la pneumonía y las infecciones de las vías urinarias las causas más comunes de fiebre. Uno de cada 20 pacientes no tenía una enfermedad infecciosa. Palabras claves: región del Caribe, medicina de emergencia, epidemiología, fiebr

Correction to: The early identification of disease progression in patients with suspected infection presenting to the emergency department: A multi-centre derivation and validation study (Critical Care (2019) 23 (40) DOI: 10.1186/s13054-019-2329-5)

In the publication of this article [1], there are two errors in contributing author affiliations. This has now been included in this correction article

Use of Non-vitamin K Antagonist Oral Anticoagulants for Stroke Prevention across the Stroke Spectrum: Progress and Prospects.

Multiple randomized controlled trials and many real-world evidence studies have consistently shown that non-vitamin K antagonist oral anticoagulants (NOACs) are preferable to vitamin K antagonists for thromboembolic stroke prevention in the majority of patients with atrial fibrillation (AF). However, their role in the management of patients with AF and comorbidities, as well as in other patient populations with a high risk of stroke, such as patients with prior embolic stroke of undetermined source (ESUS) and those with atherosclerosis, is less clear. There is now increasing evidence suggesting that NOACs have a beneficial effect in the prevention of stroke in patients with AF and comorbidities, such as renal impairment and diabetes. In addition, while studies investigating the efficacy and safety of NOACs for the prevention of secondary stroke in patients with a history of ESUS demonstrated neutral results, subanalyses suggested potential benefits in certain subgroups of patients with ESUS. One NOAC, rivaroxaban, has also recently been found to be effective in reducing the risk of stroke in patients with chronic cardiovascular disease including coronary artery disease and peripheral artery disease, further broadening the patient groups that may benefit from NOACs. In this article, we will review recent evidence for the use of NOACs across the stroke spectrum in detail, and discuss the progress and future prospects in the different stroke areas

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log <sub>10</sub> increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline