Model-based evaluation and optimization of cardiac monitoring protocols for adjuvant treatment of breast cancer with trastuzumab.

Purpose: Trastuzumab treatment is associated with occurrence of cardiac toxicity, for which monitoring of the left ventricular ejection fraction (LVEF) is indicated. The performance of the currently used monitoring protocol as defined in the summary of product characteristics (SPC) is however unknown. The objective of this analysis was to develop a model-based framework for evaluation and optimization of cardiac monitoring strategies.

A model of hypertension and proteinuria in cancer patients treated with the anti-angiogenic drug E7080.

Hypertension and proteinuria are commonly observed side-effects for anti-angiogenic drugs targeting the VEGF pathway. In most cases, hypertension can be controlled by prescription of anti-hypertensive (AH) therapy, while proteinuria often requires dose reductions or dose delays. We aimed to construct a pharmacokinetic-pharmacodynamic (PK-PD) model for hypertension and proteinuria following treatment with the experimental VEGF-inhibitor E7080, which would allow optimization of treatment, by assessing the influence of anti-hypertensive medication and dose reduction or dose delays in treating and avoiding toxicity.

Contraindications for anticoagulation in older patients with atrial fibrillation; a narrative review.

Background: Oral anticoagulation (OAC) is the most effective treatment to prevent strokes in patients with atrial fibrillation (AF). Many older patients are not prescribed OAC.

Objective: To explore which co-morbid conditions in older patients with AF have been associated with under-treatment with OAC, or were used as exclusion criteria for trials, or have been associated with increased risk of bleeding.

Reasons for undertreatment with oral anticoagulants in frail geriatric outpatients with atrial fibrillation: a prospective, descriptive study.

Objectives: The main aims of the study were to explore whether oral anticoagulation (OAC) for atrial fibrillation (AF) in geriatric outpatients is prescribed in accordance with international (American College of Cardiology/American Heart Association/European Society of Cardiology [ACC/AHA/ESC]) and Dutch national guidelines for the general practitioner (GP) and to identify whether age and selected co-morbid conditions are associated with undertreatment. As a secondary objective, we wanted to establish how many patients discontinue OAC because of major bleeding.

Methods: In 2004, at the first visit of all patients to the geriatric day clinic of the Slotervaart Hospital in Amsterdam, the Netherlands, demographic data, Mini-Mental State Examination score, medical history, Charlson Comorbidity Index score, and data on medication use and changes were documented.

Treatment of hypertension in an elderly outpatient population in the Netherlands.

Background: The treatment of older patients with hypertension has been controversial-in addition to uncertainty regarding appropriate blood pressure (BP) targets in the very old, there are concerns that excessive BP lowering could result in adverse events such as falls, stroke, and cognitive problems. The Hypertension in the Very Elderly Trial (HYVET), however, found that lowering BP in patients aged > or =80 years was associated with decreased morbidity and mortality.

Objective: This study compared the findings of HYVET with data from a population of elderly outpatients with hypertension in a clinical practice setting.

Cardiopulmonary imaging, functional and laboratory studies in sickle cell disease associated pulmonary hypertension.

Pulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle cell disease (SCD) and is an independent risk factor for early death. In this study, we aimed to determine the value of general laboratory testing, plain chest radiography, electrocardiography (ECG), high-resolution computer tomography (HRCT) of the thorax, pulmonary function testing, and plasma N-terminal brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in patients with SCD-related PHT. A cohort of 85 ambulatory sickle cell patients were prospectively screened for PHT with echocardiography (defined as a tricuspid regurgitation flow velocity of > or =2.

Sickle cell disease-related organ damage occurs irrespective of pain rate: implications for clinical practice.

In daily clinical practice, the frequency of painful crises (pain rate) is an important parameter of sickle cell disease severity. We assessed the prevalence of sickle cell disease-related organ damage and complications and their relation to pain rate. Organ damage and history of vaso-occlusive complications were obtained via systematic screening of consecutive patients and by chart review.

Large and medium-sized pulmonary artery obstruction does not play a role of primary importance in the etiology of sickle-cell disease-associated pulmonary hypertension.

Background: Pulmonary hypertension (PHT) occurs in approximately 30% of adult patients with sickle-cell disease (SCD) and is a risk factor for early death. The potential role of pulmonary artery obstruction, whether due to emboli or in situ thrombosis, in the etiology of SCD-related PHT is unknown.

Methods: Consecutive SCD patients were screened for PHT (defined as a tricuspid regurgitant jet flow velocity > or = 2.

Dengue disease severity in Indonesian children: an evaluation of the World Health Organization classification system.

Background: Dengue disease severity is usually classified using criteria set up by the World Health Organization (WHO). We aimed to assess the diagnostic accuracy of the WHO classification system and modifications to this system, and evaluated their potential practical usefulness.

Methods: Patients, admitted consecutively to the hospital with severe dengue, were classified using the WHO classification system and modifications to this system.

ADAMTS13 activity in sickle cell disease.

Sickle red blood cell (SRBC)-endothelial adhesion plays a central role in sickle cell disease (SCD)-related vaso-occlusion. As unusually large von Willebrand factor (ULVWF) multimers mediate SRBC-endothelial adhesion, we investigated the activity of ADAMTS13, the metalloprotease responsible for cleaving ULVWF multimers, in SCD. ADAMTS13 activity was determined using a quantitative immunoblotting assay.

Prognostic value of echocardiographically assessed right ventricular dysfunction in patients with pulmonary embolism.

Background: Echocardiographically assessed right ventricular dysfunction is increasingly used to guide more aggressive therapy in hemodynamically stable patients with acute pulmonary embolism (PE). However, the prognostic value of right ventricular dysfunction in these patients is still unclear.

Methods: We systemically reviewed the literature to assess the prevalence of echocardiographic right ventricular dysfunction and the association with adverse outcomes in patients with PE who had this condition.

Anti-inflammatory and anticoagulant effects of pravastatin in patients with type 2 diabetes.

Objective: Type 2 diabetes is associated with increased plasma concentrations of coagulation and inflammation markers. Different studies have shown that treatment with hydroxymethylglutaryl-CoA reductase inhibitors (statins) is associated with antithrombotic and anti-inflammatory effects in addition to a cholesterol-lowering effect. Our objective was to evaluate the effect of pravastatin (40 mg/day) on coagulation and inflammation markers in type 2 diabetic patients.

Oral contraceptives and inherited thrombophilia: a gene-environment interaction with a risk of venous thrombosis?

There are indications in the literature that asymptomatic women with an inherited thrombophilic defect who use oral contraceptive have an increased risk of venous thrombosis. There are no consistent data regarding the thrombotic risk in users of oral contraceptives with an inherited thrombophilic defect and personal history of venous thrombosis. Selective genetic screening on the basis of clinical judgment, and family and personal history, instead of universal screening, may be useful before oral contraceptives are prescribed.

Travel and the risk of symptomatic venous thromboembolism.

Whether long-distance travel and symptomatic venous thromboembolism (VTE) are associated is debated. On the basis of the available literature a fair risk estimate cannot be obtained. We estimated an accurate odds ratio for the relationship between recent travelling and symptomatic VTE.

Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism.

D-dimer blood tests have been suggested to rule out pulmonary embolism. Despite evidence of the safety of withholding anticoagulant treatment in patients with suspected pulmonary embolism and a normal D-dimer assay result, clinicians remain reluctant to use a D-dimer assay as a sole diagnostic test. This prospective study in 314 consecutive inpatients and outpatients investigates the relation between the diagnostic accuracy of D-dimer plasma concentration and pulmonary embolus location.