Corrigendum to "Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births".

[This corrects the article DOI: 10.1155/2017/2810202.].

Diagnosing and treating antiphospholipid syndrome: a consensus paper.

INTRODUCTION: The antiphospholipid syndrome (APS) is defined by the occurrence of venous and/or arterial thrombosis and/or pregnancy-related morbidity, combined with the presence of antiphospholipid antibodies (aPL) and/or a lupus anticoagulant (LAC). Large, controlled, intervention trials in APS are limited. This paper aims to provide clinicians with an expert consensus on the management of APS. METHODS: Relevant papers were identified by literature search. Statements on diagnostics and treatment were extracted. During two consensus meetings, statements were discussed, followed by a Delphi procedure. Subsequently, a final paper was written. RESULTS: Diagnosis of APS includes the combination of thrombotic events and presence of aPL. Risk stratification on an individual base remains challenging. 'Triple positive' patients have highest risk of recurrent thrombosis. aPL titres > 99th percentile should be considered positive. No gold standard exists for aPL testing; guidance on assay characteristics as formulated by the International Society on Thrombosis and Haemostasis should be followed. Treatment with vitamin K-antagonists (VKA) with INR 2.0-3.0 is first-line treatment for a first or recurrent APS-related venous thrombotic event. Patients with first arterial thrombosis should be treated with clopidogrel or VKA with target INR 2.0-3.0. Treatment with direct oral anticoagulants is not recommended. Patients with catastrophic APS, recurrent thrombotic events or recurrent pregnancy morbidity should be referred to an expert centre. CONCLUSION: This consensus paper fills the gap between evidence-based medicine and daily clinical practice for the care of APS patients.

Identifying patients with bacterial infections using a combination of C-reactive protein, procalcitonin, TRAIL, and IP-10 in the emergency department: a prospective observational cohort study.

OBJECTIVES: The aim was to effectively reduce the unnecessary use of broad spectrum antibiotics in the emergency department (ED), patients with bacterial infections need to be identified accurately. We investigated the diagnostic value of a combination of biomarkers for bacterial infections, C-reactive protein (CRP), and procalcitonin (PCT), together with biomarkers for viral infections, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and interferon-gamma-induced protein-10 (IP-10), in identifying suspected and confirmed bacterial infections in a general ED population with fever. METHODS: This is a sub-study in the HiTEMP cohort. Patients with fever were included during ED triage, and blood samples were obtained. Using both diagnostics and expert panel analysis, all patients were classified as having either suspected or confirmed bacterial infections, or non-bacterial disease. Using multivariable logistic regression analysis, three biomarker models were analysed: model 1, CRP, TRAIL, IP-10; model 2, PCT, TRAIL, IP-10; and model 3, CRP, PCT, TRAIL, IP-10. RESULTS: A total of 315 patients were included, of whom 228 patients had a suspected or confirmed bacterial infection. The areas under the curve for the combined models were the following: model 1, 0.730 (95% CI 0.665-0.795); model 2, 0.748 (95% CI 0.685-0.811); and model 3, 0.767(95% CI 0.704-0.829). CONCLUSIONS: These findings show that a combination of CRP, PCT, TRAIL and IP-10 can identify bacterial infections with higher accuracy than single biomarkers and combinations of a single bacterial biomarkers combined with TRAIL and IP-10.

Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicentre non-inferiority randomized clinical trial (HiTEMP study).

OBJECTIVES: Overuse of broad-spectrum antibiotics in emergency departments (EDs) results in antibiotic resistance. We determined whether procalcitonin (PCT) -guided therapy can be used to reduce antibiotic regimens in EDs by investigating efficacy, safety and accuracy. METHODS: This was a non-inferiority multicentre randomized clinical trial, performed in two Dutch hospitals. Adult patients with fever ≥38.2°C (100.8°F) in triage were randomized between standard diagnostic workup (control group) and PCT-guided therapy, defined as standard workup with the addition of one single PCT measurement. The treatment algorithm encouraged withholding antibiotic regimens with PCT <0.5 µg/L, and starting antibiotic regimens at PCT ≥0.5 µg/L. Exclusion criteria were immunocompromised conditions, pregnancy, moribund patients, patients <72 h after surgery or requiring primary surgical intervention. Primary outcomes were efficacy, defined as number of prescribed antibiotic regimens; safety, defined as combined safety end point consisting of 30 days mortality, intensive-care unit admission, ED return visit within 2 weeks; accuracy, defined as sensitivity, specificity and area-under-the-curve (AUC) of PCT for bacterial infections. Non-inferiority margin for safety outcome was 7.5%. RESULTS: Between August 2014 and January 2017, 551 individuals were included. In the PCT-guided group (n = 275) 200 (73%) patients were prescribed antibiotic regimens, in the control group (n = 276) 212 (77%) patients were prescribed antibiotics (p 0.28). There was no significant difference in combined safety end point between the PCT-guided group, 29 (11%), and control group, 46 (16%) (p 0.16), with a non-inferiority margin of 0.46% (n = 526). AUC for confirmed bacterial infections for PCT was 0.681 (95% CI 0.633-0.730), and for CRP was 0.619 (95% CI 0.569-0.669). CONCLUSIONS: PCT-guided therapy was non-inferior in terms of safety, but did not reduce prescription of antibiotic regimens in an ED population with fever. In this heterogeneous population, the accuracy of PCT in diagnosing bacterial infections was poor. TRIAL REGISTRATION IN NETHERLANDS TRIAL REGISTER: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4949.

Statins for prevention of cardiovascular disease in systemic lupus erythematosus.

OBJECTIVE: In systemic lupus erythematosus (SLE), cardiovascular disease (CVD) is an important cause of long-term morbidity, which could be affected by statin use. Here we review the evidence for the use of statins for the prevention of CVD in patients with SLE. METHODS: The PubMed database was searched using a query combining SLE and statins. RESULTS: The search yielded nine relevant clinical studies. Seven studies reported on radiological findings that correlate with atherosclerosis and mainly revealed that statin treatment resulted in a slight decrease in progression of carotid intima-media thickness and an increase in flow-mediated vasodilatation. Two studies investigated CVD and mortality. In a group of SLE patients that had received a kidney transplantation, three of 23 statin-treated SLE patients experienced cardiac events compared with four of ten placebo- reated controls. Moreover, in a retrospectively studied cohort of SLE patients with dyslipidaemia, statin treatment in 777 patients was associated with a large decrease in coronary heart disease (hazard ratio [HR] = 0.20), cerebrovascular disease (HR = 0.14), end-stage renal disease (HR = 0.22) and mortality (HR = 0.44) compared with 1317 patients that had not been prescribed statins. However, the latter retrospective study was subject to bias and causality can only be proven in a randomised trial. Statins showed a good safety profile in SLE patients. CONCLUSION: Whilst awaiting new prospective randomised studies, we recommend prescription of statins in SLE patients with increased cardiovascular risk according to the current recommendations for cardiovascular risk management in rheumatoid arthritis.

Hydroxychloroquine Use in Lupus Patients during Pregnancy Is Associated with Longer Pregnancy Duration in Preterm Births.

OBJECTIVE: To investigate the effect of hydroxychloroquine (HCQ) in pregnant women with systemic lupus erythematosus (SLE). METHODS: In SLE pregnancies of a single Dutch center (2000-2015), lupus activity and flares before and during pregnancy and postpartum were assessed using the SLE Disease Activity Index (SLEDAI)/SLEPDAI (SLEDAI adjusted for pregnancy). The association between HCQ use and pregnancy outcomes (early spontaneous abortion, fetal death, and preterm and term live birth) was analyzed using generalized estimating equations (GEE) accounting for the occurrence of multiple pregnancies per patient. Analyses were adjusted for antiphospholipid antibody (aPL) status. RESULTS: 110 pregnancies (63 mostly Caucasian patients) were included, of which, in 30, HCQ was used; overall occurrence of flares was low (non-HCQ group: 5 mild (6.4%) and 2 severe (2.6%); HCQ group: 2 mild (6.7%) and no severe flares). The HCQ group showed a trend towards lower dosage of prednisone (OR 0.2 (95% CI 0.0-1.4); p = 0.10). Pregnancy outcomes were comparable between groups. Among preterm live births, pregnancy duration was significantly longer in HCQ users (2.4 weeks (95% CI 1.0-3.8; p ≤ 0.001)). CONCLUSION: HCQ use was associated with longer pregnancy duration in the vulnerable preterm birth population, underscoring the beneficial effect of HCQ use during pregnancy.

Climate Factors as Important Determinants of Dengue Incidence in Curaçao.

Macro- and microclimates may have variable impact on dengue incidence in different settings. We estimated the short-term impact and delayed effects of climate variables on dengue morbidity in Curaçao. Monthly dengue incidence data from 1999 to 2009 were included to estimate the short-term influences of climate variables by employing wavelet analysis, generalized additive models (GAM) and distributed lag nonlinear models (DLNM) on rainfall, temperature and relative humidity in relation to dengue incidence. Dengue incidence showed a significant irregular 4-year multi-annual cycle associated with climate variables. Based on GAM, temperature showed a U-shape, while humidity and rainfall exhibited a dome-shaped association, suggesting that deviation from mean temperature increases and deviation from mean humidity and rainfall decreases dengue incidence, respectively. Rainfall was associated with an immediate increase in dengue incidence of 4.1% (95% CI: 2.2-8.1%) after a 10-mm increase, with a maximum increase of 6.5% (95% CI: 3.2-10.0%) after 1.5 month lag. A 1 °C decrease of mean temperature was associated with a RR of 17.4% (95% CI: 11.2-27.0%); the effect was inversed for a 1°C increase of mean temperature (RR= 0.457, 95% CI: 0.278-0.752). Climate variables are important determinants of dengue incidence and provide insight into its short-term effects. An increase in mean temperature was associated with lower dengue incidence, whereas lower temperatures were associated with higher dengue incidence.

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 degrees 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.

Epidemiology of febrile diseases in the emergency department of a Caribbean Island: the Curaçao experience / Epidemiología de las enfermedades febriles en el departamento de emergencias de una Isla Caribeña: la experiencia de Curazao

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.

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.

Procalcitonin as a potent marker of bacterial infection in febrile Afro-Caribbean patients at the emergency department.

Procalcitonin (PCT) has been shown to be of additional value in the work-up of a febrile patient. This study is the first to investigate the additional value of PCT in an Afro-Caribbean febrile population at the emergency department (ED) of a general hospital. Febrile patients were included at the ED. Prospective, blinded PCT measurements were performed in patients with a microbiologically or serologically confirmed diagnosis or a strongly suspected diagnosis on clinical grounds. PCT analysis was performed in 93 patients. PCT levels differentiated well between confirmed bacterial and confirmed viral infection (area under the curve [AUC] of 0.82, sensitivity 85%, specificity 69%, cut-off 0.24 ng/mL), between confirmed bacterial infection and non-infectious fever (AUC of 0.84, sensitivity 90%, specificity 71%, cut-off 0.21 ng/mL) and between all bacterial infections (confirmed and suspected) and non-infectious fever (AUC of 0.80, sensitivity 85%, specificity 71%, cut-off 0.21 ng/mL). C-reactive protein (CRP) levels were shown to be less accurate when comparing the same groups. This is the first study showing that, in a non-Caucasian febrile population at the ED, PCT is a more valuable marker of bacterial infection than CRP. These results may improve diagnostics and eventually decrease antibiotic prescriptions in resource-limited settings.

One-year epidemiology of fever at the Emergency Department.

BACKGROUND: Although fever is recognised as a major presentation symptom at Emergency Departments (EDs) and is often used as a rationale for the institution of antibiotics, few studies describing patients with fever as the sole inclusion criterion at the ED of a general hospital have been performed. The objective of this study is to describe epidemiology of non-surgical febrile patients at the ED and to identify risk factors for adverse outcome. METHODS: Blood, sputum, urine and faeces cultures, urine sediments and throat swaps for viral diagnostics were obtained from febrile ED patients. Outcome parameters were bacterial/viral infection, non-bacterial/non-viral infection, non-infectious febrile disease; mortality, hospital admission, admission to the intensive care unit (ICU) and length of hospital stay. RESULTS: 213 Patients were included (87.8% were hospitalised, 8.5% were admitted to ICU, 4.2% died). In 75 patients (35.2%), bacterial infection was confirmed; in 78 patients (36.6%) bacterial infection was suspected. In nine patients (4.2%), viral diagnosis was confirmed; in six patients (2.8%), a viral condition was suspected. The most frequently encountered infection was bacterial pneumonia (58 patients, 27.2%). Only older age was correlated with mortality (ρ=0.176, p=0.01). CONCLUSION: A majority of the febrile patients were admitted to the hospital, mostly for bacterial infection. An overall mortality rate of 4.2% was registered. Only a few risk factors for adverse outcome could be identified in this cohort. Overall, the outcome of patients presenting with fever at the ED is rather benign.

The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from non-infectious fever.

Fever is not only observed in the course of a bacterial or viral infection, but can be a symptom of, for instance, auto-immune, malignant or thromboembolic disease. Determining the etiology of fever in a fast and reliable way is of pivotal importance, as different causes of fever may ask for different therapies. Neither clinical signs and symptoms, nor traditional biomarkers, such as CRP, leukocytes and ESR have sufficient sensitivity and specificity to guide treatment decisions. In this review we focus on the value of traditional and newer biomarkers in non-infectious febrile diseases. Procalcitonin (PCT) seems to be the most helpful laboratory marker for the differentiation of causes of fever, particularly in autoimmune, autoinflammatory and malignant diseases.