Authors/Task Force Members: Adam Torbicki, Chairperson (Poland)*, Arnaud Perrier (Switzerland), Stavros Konstantinides (Germany), Giancarlo Agnelli (Italy), Nazzareno Galiè (Italy), Piotr Pruszczyk (Poland), Frank Bengel (USA), Adrian J.B. Brady (UK), Daniel Ferreira (Portugal), Uwe Janssens (Germany), Walter Klepetko (Austria), Eckhard Mayer (Germany), Martine Remy-Jardin (France), and Jean-Pierre Bassand (France)

Guidelines on diagnosis and management of acute pulmonary embolism

Despite the known higher risk of cardiovascular disease (CVD) in individuals with type 1 diabetes mellitus (T1DM), the pathophysiology underlying the relationship between cardiovascular events, CVD risk factors, and T1DM is not well understood. Management approaches to CVD reduction have been extrapolated in large part from experience in type 2 diabetes mellitus (T2DM), despite the longer duration of disease in T1DM than in T2DM and the important differences in the underlying pathophysiology. Furthermore, the phenotype of T1DM is changing. As a result of the findings of the Diabetes Control and Complications Trial (DCCT), which compared intensive glycemic control with usual care, and its follow-up observational study, Epidemiology of Diabetes Interventions and Complications (EDIC), intensive management of diabetes mellitus (DM) has become the standard of care and has led to increasing longevity. However, our understanding of CVD in T1DM comes in large part from the previous era of less intensive glycemic control. More intensive glycemic control is associated with significant risk of weight gain, which may be magnified by the obesity epidemic. There is growing interest in better understanding the adverse effects of glycemia, the prevalence and type of lipid abnormalities in T1DM, the prognostic role of albuminuria and renal insufficiency, and the role of blood pressure (BP) in CVD. Obesity-associated metabolic abnormalities such as the proinflammatory state likely modify CVD risk in T1DM; however, the effect may be different from what is seen in T2DM. These concepts, and how they may affect management, have not been fully explored.

The present review will focus on the importance of CVD in patients with T1DM. We will summarize recent observations of potential differences in the pathophysiology of T1DM compared with T2DM, particularly with regard to atherosclerosis. We will explore the implications of these concepts for treatment of CVD risk factors in patients with …

Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association.

Background: Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated. Methods and Findings: The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults ($18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with $1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean6SD CHADS2 score was 1.961.2, and 57.2% had a score $2. Mean CHA2DS2-VASc score was 3.261.6, and 8,957 (84.4%) had a score $2. Overall, 38.0% of patients with a CHADS2 score $2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy. Conclusions: These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke.

/pdf/risk-profiles-and-antithrombotic-treatment-of-patients-newly-33pkkx1y6h.pdf

Risk Profiles and Antithrombotic Treatment of Patients Newly Diagnosed with Atrial Fibrillation at Risk of Stroke: Perspectives from the International, Observational, Prospective GARFIELD Registry

This paper reviews the published experience with plasma measurement of D-dimer (DD), a specific degradation product of crosslinked fibrin, in the diagnostic approach of venous thromboembolism (VTE). Pooling 11 studies (with weighting of the figures according to sample size) with a total of 1337 patients clinically suspected of deep venous thrombosis (DVT) (prevalence of DVT 35%) disclosed an average weighted sensitivity of 96.8% (95% CI: 95.2-98.4) and specificity of 35.2% (95% CI: 32.0-38.4) for the presence of DVT when the ELISA technique was used. In 908 patients suspected of pulmonary embolism (PE) from 9 trials (prevalence of PE 38%), the ELISA technique was associated with a weighted sensitivity of 96.8% (95% CI: 95.0-98.6) and specificity of 45.1% (95% CI: 40.8-49.4) for the disease. Figures obtained with latex assays were definitely lower, precluding their use in the diagnostic approach of VTE. These results show that a low concentration of plasma DD measured by the ELISA technique (usually less than 500 micrograms/l) might be used to rule out VTE in clinically suspected patients. Increased plasma concentrations are of no utility because of the low specificity of this test result. The clinical usefulness of the DD ELISA test should now be assessed in management trials under routine conditions, in the frame of clinical decision-making diagnostic processes. Lastly, the promising data obtained in a small number of asymptomatic, postoperative patients at risk of VTE deserve confirmation before the test can be recommended for initial screening in thrombo-prophylactic trials.

Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview.

Percutaneous Left Atrial Appendage Suture Ligation Using the LARIAT Device in Patients With Atrial Fibrillation: Initial Clinical Experience

The main aims of the study were to explore whether oral anti-coagulation (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. 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. The presence of AF was established by assessment of medical history information obtained by the GP, the history taken from patients and their caregivers, and the results of clinical evaluation, including ECG findings. Associations between the use of OAC, demographic data and co-morbid conditions registered in the Dutch NHG (Nederlands Huisartsen Genootschap [Dutch College of General Practitioners]) standard for GPs as risk factors for stroke or contraindications to the use of OAC were analysed. The reasons for discontinuing OAC were assessed after 4 years by requesting the information from the anticoagulation services or the GP. At the time of the initial visit, 17.5% of the 807 outpatients had chronic AF (n= 135) or were known to have paroxysmal AF (n = 6). The mean age of the 141 patients in this cohort was 84.3 years (SD 6.2 years). Co-morbid conditions increasing the risk of stroke were present in 129 patients (91.5%). Contraindications to the use of OAC were observed in 118 patients (83.7%). Of the 116 patients with AF in their history before their visit, 57.8% were being treated with OAC at the time of their visit. After comprehensive geriatric assessment, 73 (51.8%) of the 141 patients with chronic or paroxysmal AF were continued on OAC. Of the 141 patients with chronic or paroxysmal AF, 110 (78.0%) had both extra stroke risk factors and contraindications to the use of OAC. Only increasing age was significantly and independently associated with not being prescribed anticoagulants (p<0.001). At the 4-year follow-up, OAC had been discontinued in 5.5% of patients because of major bleeding; three patients (4.1%) taking OAC had died as a result of major bleeding, and one other patient had discontinued treatment because of a major, non-lethal bleeding episode. Applying the NHG standard for appropriate prescription, and disregarding age as a risk factor or contraindication, in this population, 14 of 141 patients (9.9%) were inappropriately prescribed OAC, salicylates or no prophylaxis. Since only patient age was associated with not prescribing OAC in this study, higher age still seems to be considered the most important contraindication to anticoagulation therapy. Implementation of better models for stratifying bleeding risk in the frail elderly is needed. After 4 years, the cumulative rate of bleeding causing discontinuation of anticoagulation therapy in this usual-care study of frail older patients was not alarmingly higher than in other usual-care studies.

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

To avoid angiography in patients with clinically suspected pulmonary embolism and non-diagnostic lung scan results, the use of D-dimer has been advocated. We assessed plasma samples of 151 consecutive patients with clinically suspected pulmonary embolism. Lung scan results were: normal (43), high probability (48) and non-diagnostic (60; angiography performed in 43; 12 pulmonary emboli). Reproducibility, cut-off values, specificity, and percentage of patients in whom angiography could be avoided (with sensitivity 100%) were determined for two latex and four ELISA assays. The latex methods (cut-off 500 micrograms/l) agreed with corresponding ELISA tests in 83% (15% normal latex, abnormal ELISA) and 81% (7% normal latex, abnormal ELISA). ELISA methods showed considerable within- (2-17%) and between-assay variation (12-26%). Cut-off values were 25 micrograms/l (Behring), 50 micrograms/l (Agen), 300 micrograms/l (Stago) and 550 micrograms/l (Organon). Specificity was 14-38%; in 4-15% of patients angiography could be avoided. We conclude that latex D-dimer assays appear not useful, whereas ELISA methods may be of limited value in the exclusion of pulmonary embolism.

A comparative analysis of D-dimer assays in patients with clinically suspected pulmonary embolism.

Background: Increased age is associated with polypharmacy. Polypharmacy is a risk factor for severe adverse drug reactions (ADRs) and is associated with an increased risk of mortality. Objectives: The main goal of the current study was to describe the frequency and relevancy of discrepancies in drug use in Dutch geriatric outpatients as reported by the patients and their caregivers, documented by the referring general practitioner (GP), and registered by the public pharmacy. The frequency of medication discrepancy adverse patient events (MDAPEs) was also recorded. In addition, possible contributing factors—such as increasing age, cognitive status and depressive symptoms, the number of medications used, the number of physicians visited by the patient, and the presence of a caregiver to supervise medication use—were studied. Methods: This was a prospective descriptive study conducted at the geriatric outpatient clinic of a teaching hospital. Between January 1 and May 1, 2005, consecutive patients were included if they were aged >65 years, reported use of ≥1 medication, and if they could understand the goals and consequences of participating in the study. The medications described by geriatric patients and their caregivers were compared with the drugs listed by their GP. The pharmacies of the referred patients were asked to send a description of the drugs distributed in the 6 months preceding the patient's visit to the geriatric outpatient clinic. The classification of ADRs and undertreatment as clinically relevant was done by study investigators who were blinded for the presence of discrepancy. Results: A total of 120 outpatients were included. The mean (SD) age of the study patients was 82.3 (6.8) years; 71.7% were women. Of the 120 patients, 113 patients (94.2%) reported taking >1 drug and 88 (73.3%) were prescribed ≥4 drugs. At least 1 discrepancy between the medication lists of the patients, GP, or pharmacy was present in 104 of the 120 patients (86.7%). In 90 patients (75.0%), there was ≥1 discrepancy between the medication reported by the patient and the GP. Patients with ≥1 discrepancy reported taking a higher mean number of drugs and had more prescribing physicians in addition to their GP. Twenty-nine patients (24.2%) experienced an MDAPE involving the use of drugs the GP had not correctly described in the letter of referral. The pharmacy was unaware of the use of medication involved in an MDAPE in 2 patients. Conclusions: Geriatricians should assume that the medication lists supplied by GPs are incomplete or incorrect, and be aware that in ~25% of patients, symptoms may be caused by medication use inaccurately described in the referral. Reports by the community pharmacy may supply valuable additional information. Because there are also discrepancies between patients and pharmacies, medication use from a database—with data from prescribing physicians and pharmacy systems—will still have to be confirmed by the patient.

Discrepancies in reported drug use in geriatric outpatients: relevance to adverse events and drug-drug interactions.

The growing prevalence rate of pediatric obesity, which is frequently accompanied by several cardiometabolic risk factors, has become a serious global health issue. To date, little is known regarding differences for cardiometabolic risk factors (prevalence and means) in children from different countries. In the present review, we aimed to provide a review for the available evidence regarding cardiometabolic risk factors in overweight pediatric populations. We therefore provided information with respect to the prevalence of impaired fasting glucose/impaired glucose tolerance, high triglycerides, low HDL-cholesterol and hypertension (components of the metabolic syndrome) among cohorts from different countries. Moreover, we aimed to compare the means of glucose and lipid levels (triglycerides and HDL-cholesterol) and systolic/diastolic blood pressure values. After careful selection of articles describing cohorts with comparable age and sex, it was shown that both prevalence rates and mean values of cardiometabolic risk factors varied largely among cohorts of overweight children. After ranking for high/low means for each cardiometabolic risk parameter, Dutch-Turkish children and children from Turkey, Hungary, Greece, Germany and Poland were in the tertile with the most unfavorable risk factor profile overall. In contrast, cohorts from Norway, Japan, Belgium, France and the Dominican Republic were in the tertile with most favorable risk profile. These results should be taken with caution, given the heterogeneity of the relatively small, mostly clinical cohorts and the lack of information concerning the influence of the values of risk parameters on true cardiometabolic outcome measures in comparable cohorts. The results of our review present a fair estimation of the true differences between cardiometabolic risk profiles among pediatric cohorts worldwide, based on available literature.

/pdf/cardiometabolic-risk-variables-in-overweight-and-obese-36xxq5jmci.pdf

Cardiometabolic risk variables in overweight and obese children: a worldwide comparison

Background
Laparoscopic Roux-en-Y gastric bypass (LRYGB) is an effective treatment for morbid obesity, but might aggravate gastrointestinal complaints and food intolerance. The long-term prevalence of these symptoms has not been well studied.

Methods
In a cross-sectional study, all patients who underwent primary LRYGB from May to October 2012 were approached 2 years after surgery to complete a general health questionnaire, the Gastrointestinal Symptom Rating Scale (GSRS), and a food intolerance questionnaire. The results were compared with those for a control group of morbidly obese patients.

Results
A total of 249 patients were included for analysis, representing a response rate of 93·9 per cent. Mean(s.d.) total weight loss was 30·8(8·7) per cent. The total mean GSRS score was higher in patients who had LRYGB (median 2·19 versus 1·75 in unoperated patients; P < 0·001); the difference in symptoms of indigestion was most notable (P < 0·001). Food intolerance for specific products was reported by 70·7 (95 per cent c.i. 64·8 to 76·0) per cent of the postoperative patients, for a median of 4 foods. There was a positive correlation between food intolerance and score on the GSRS. There was no correlation between either food intolerance or the total mean GSRS score and weight loss, but there was a correlation between weight loss and abdominal pain.

Conclusion
At 2 years after surgery, patients undergoing LRYGB for morbid obesity have more gastrointestinal complaints than obese controls. Food intolerance is a common side-effect of LRYGB independent of degree of weight loss or the presence of other abdominal symptoms.

/pdf/gastrointestinal-symptoms-and-food-intolerance-2-years-after-z4otvu5tq6.pdf

Desiderius P M Brandjes

Papers

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

A comparative analysis of D-dimer assays in patients with clinically suspected pulmonary embolism.

Discrepancies in reported drug use in geriatric outpatients: relevance to adverse events and drug-drug interactions.

Cardiometabolic risk variables in overweight and obese children: a worldwide comparison

Gastrointestinal symptoms and food intolerance 2 years after laparoscopic Roux-en-Y gastric bypass for morbid obesity