Should relational effects be considered in health care priority setting?

It is uncontroversial to claim that the extent to which health care interventions benefit patients is a relevant consideration for health care priority setting. However, when effects accrue to the individual patient, effects of a more indirect kind may accrue to other individuals as well, such as the patient's children, friends, or partner. If, and if so how, such relational effects should be considered relevant in priority setting is contentious. In this paper, we illustrate this question by using disease-modifying drugs for Alzheimer's disease as a case in point. The ethical analysis begins by sketching the so-called prima facie case for ascribing moral weight to relational effects and then moves on to consider a number of objections to it. We argue that, whereas one set of objections may be dismissed, there is another set of arguments that poses more serious challenges for including relational effects in priority setting.

Novel drug candidates targeting Alzheimer's disease: ethical challenges with identifying the relevant patient population.

Intensive research is carried out to develop a disease-modifying drug for Alzheimer's disease (AD). The development of drug candidates that reduce Aß or tau in the brain seems particularly promising. However, these drugs target people at risk for AD, who must be identified before they have any, or only moderate, symptoms associated with the disease. There are different strategies that may be used to identify these individuals (eg, population screening, cascade screening, etc). Each of these strategies raises different ethical challenges. In this paper, we analyse these challenges in relation to the risk stratification for AD necessary for using these drugs. We conclude that the new drugs must generate large health benefits for people at risk of developing AD to justify the ethical costs associated with current risk stratification methods, benefits much larger than current drug candidates have. This conclusion raises a new set of ethical questions that should be further discussed.

Pharmaceuticals and Environment: a web-based decision support for considering environmental aspects of medicines in use.

PURPOSE: The database Pharmaceuticals and Environment is a non-commercial, freely available web-based decision support presenting compiled environmental information for pharmaceutical substances. It was developed by Region Stockholm and launched in 2016 at janusinfo.se. The purpose of this paper is to present the database, report on its current use, and reflect on lessons learned from developing and managing the database. METHODS: A standard operating procedure describes the work and content of the database, e.g., how information is retrieved, processed, and presented. Google Analytics was used for metrics. Issues related to the database have been discussed and handled by a reference group. The experiences from this work are presented. RESULTS: The database contains environmental hazard and risk information, primarily gathered from regulatory authorities and pharmaceutical companies. There are also assessments comparing substances within some groups of pharmaceuticals. The database is used by the Swedish Drug and Therapeutics Committees to include environmental aspects when recommending pharmaceuticals for health care providers. Page views show that users primarily look for information on commonly used substances, e.g., diclofenac and paracetamol/acetaminophen. Major problems for the development of the database are lack of data, lack of transparency, and discrepancies in the available environmental information. CONCLUSION: In the absence of an adequate decision support produced by the regulatory authorities, we find the database Pharmaceuticals and Environment to be useful for Swedish Drug and Therapeutics Committees and health care providers, and it is our belief that the information can be valuable also in other settings.

Long-term quality of life and postthrombotic syndrome in women after an episode of venous thromboembolism.

Objectives To evaluate health-related quality of life after venous thromboembolism. Methods We conducted a cohort study, TEHS follow-up, including 1040 women with a first episode of venous thromboembolism and 994 women unexposed to venous thromboembolism. Patients were recruited from the "Thrombo Embolism Hormonal Study" (TEHS), a Swedish nation-wide case-control study on risk factors for venous thromboembolism in women 18-64 years of age. Quality of life was measured using SF-36 and VEINES-QoL/VEINES-Sym. Results On average there were no difference in mean SF-36 summary scales scores between exposed and unexposed women. Twenty percent of exposed women developed postthrombotic syndrome during follow-up. Women with postthrombotic syndrome had severely impaired quality of life with lower scores on all scales. Other predictors of low quality of life after venous thromboembolism were age, obesity, physical inactivity, and recurrent venous thromboembolism. Conclusion Long-term quality of life after venous thromboembolism in women was severely impaired among those developing postthrombotic syndrome, while quality of life in women not developing postthrombotic syndrome was similar to a control population.

High adherence to the 'Wise List' treatment recommendations in Stockholm: a 15-year retrospective review of a multifaceted approach promoting rational use of medicines.

OBJECTIVES: To present the 'Wise List' (a formulary of essential medicines for primary and specialised care in Stockholm Healthcare Region) and assess adherence to the recommendations over a 15-year period. DESIGN: Retrospective analysis of all prescription data in the Stockholm Healthcare Region between 2000 and 2015 in relation to the Wise List recommendations during the same time period. SETTING: All outpatient care in the Stockholm Healthcare Region. PARTICIPANTS: All prescribers in the Stockholm Healthcare Region. MAIN OUTCOME MEASURES: The number of core and complementary substances included in the Wise List, the adherence to recommendations by Anatomic Therapeutic Chemical (ATC) 1st level using defined daily doses (DDDs) adjusted to the DDD for 2015, adherence to recommendations over time measured by dispensed prescriptions yearly between 2002 and 2015. RESULTS: The number of recommended core substances was stable (175-212). Overall adherence to the recommendations for core medicines for all prescribers increased from 75% to 84% (2000 to 2015). The adherence to recommendations in primary care for core medicines increased from 80% to 90% (2005 to 2015) with decreasing range in practice variation (32% to 13%). Hospital prescriber adherence to core medicine recommendations was stable but increased for the combination core and complementary medicines from 77% to 88% (2007 to 2015). Adherence varied between the 4 therapeutic areas studied. CONCLUSIONS: High and increasing adherence to the Wise List recommendations was seen for all prescriber categories. The transparent process for developing recommendations involving respected experts and clinicians using strict criteria for handling potential conflicts of interests, feedback to prescribers, continuous medical education and financial incentives are possible contributing factors. High-quality evidence-based recommendations to prescribers, such as the Wise List, disseminated through a multifaceted approach, will become increasingly important and should be developed further to include recommendations and introduction protocols for new expensive medicines.

Cardiovascular disease and mortality after a first episode of venous thromboembolism in young and middle-aged women.

BACKGROUND: Patients with a history of venous thromboembolism (VTE) seem to have an increased risk of arterial cardiovascular disease (CVD). OBJECTIVES: To evaluate the risk of CVD and overall mortality after a first episode of VTE in women and to assess common risk factors for VTE and CVD. PATIENTS/METHODS: We performed a cohort study inviting 1433 women with a previous VTE (exposed) and 1402 women without VTE (unexposed). The cohort was derived from TEHS, a Swedish population-based case-control study on risk factors for VTE in women age 18-64years. The women were recruited in 2002-2009. During 2011 information on CVD and mortality was obtained from a questionnaire and from the Swedish Patient Register and the Cause of Death Register. Hazard ratios (HR) for CVD and their 95% confidence intervals (CI) were calculated using Cox regression. In multivariate analyses we adjusted for age, smoking, diabetes mellitus, hypertension and body mass index. RESULTS: 2108 (75%) women (mean age 47±13years) accepted participation. During the total follow up of 11,920 person years 35 (3.2%, 95% CI 0.7-2.1) among the exposed and 14 (1.4%, 95% CI 0.2-4.3) among the unexposed had any CVD event. The adjusted HR for CVD was 2.0 (95% CI 1.1-3.9) the adjusted HR for mortality was 2.3 (95% CI 1.2-4.6) CONCLUSION: Women with a previous VTE had a two-fold increased risk of CVD and overall mortality. Adjusting for cardiovascular risk factors only modestly changed the estimates.

F11 is associated with recurrent VTE in women. A prospective cohort study.

Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95% CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95% CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.

The importance of the costoclavicular space in upper limb primary deep vein thrombosis, a study with magnetic resonance imaging (MRI) technique enhanced by a blood pool agent.

BACKGROUND: Primary upper extremity deep vein thrombosis (UEDVT) can be divided into idiopathic and effort thrombosis. Anatomical factors probably play an important role in effort thrombosis, whereas the cause remains mostly unknown in idiopathic thrombosis. OBJECTIVES: The primary objective of this study was to examine the anatomy of the subclavian region and evaluate how these factors contribute to primary UEDVT. The secondary objective was to investigate if venous compression correlates with post thrombotic syndrome (PTS). PATIENTS AND METHODS: Fifteen patients and 15 controls were enrolled in the study. The subclavian region (the costoclavicular distance and vessel area) was examined by MRI enhanced by a blood-pool contrast agent (Vasovist). The MRI was performed in two arm positions: alongside and elevated. PTS and disability were quantified with the modified Villalta score and the Disability of the Arm, Shoulder and Hand (DASH) test. RESULTS: The costoclavicular distance was significantly narrower in the UEDVT patients with the arms alongside the body but there was a significant difference only in the left arm with the arms elevated. Area of the subclavian vein: When comparing the patients non-thrombotic arm with the controls, there was a significant difference only when the arms in the supine position. Disability: There was a high correlation between DASH, Villalta and VAS but no correlation between the MRI measurement and patient's symptoms or the Villalta Score. CONCLUSION: Our results suggest that primary UEDVT is dependent on the subclavian anatomy and area of vena subclavia.

Risk factors for recurrent venous thromboembolism in young and middle-aged women.

BACKGROUND: It is a matter of debate whether women with an episode of VTE associated with estrogen have a lower risk of recurrence than women with an unprovoked VTE. OBJECTIVES: To identify risk factors for recurrent VTE in women and to assess the risk of recurrent VTE associated with combined oral contraceptives (CHC) or menopausal hormone treatment (HT), compared to surgery-related and unprovoked VTE. PATIENTS/METHODS: A cohort of 974 women aged 18-64 years with a first episode of VTE were followed-up for a median time of 5.2 years. All women were previously included as cases in the Swedish nation-wide case-control study "Thrombo Embolism Hormone Study" (TEHS). Hazard ratios for recurrence were calculated using univariable and multivariable Cox proportional hazards model. RESULTS: A total of 102 patients (10%) suffered from recurrent VTE. The annual rate of recurrence was 1.0% in patients with surgery/cast, 2.0% in patients with CHC/HT and 3.2% in patients with unprovoked first VTE. Adjusted hazards ratio (HRa) for recurrence was 0.35 (95% CI 0.20-0.61) in women with VT provoked by surgery/cast while women with estrogen-associated VTE had a HRa of 0.70 (95% CI 0.43-1.20) compared to women with unprovoked VTE. CONCLUSION: Women 18-64 years are at low risk of recurrent VTE. Women with hormone associated VTE had a lower risk of recurrence than women with unprovoked VTE, but not as low as surgery/cast provoked VTE.

Self-reported family history in estimating the risk of hormone, surgery and cast related VTE in women.

BACKGROUND: Combined hormonal contraceptives, menopause hormone treatment and surgery/cast in orthopedic patients are important risk factors for venous thromboembolism (VTE) in women. OBJECTIVES: To evaluate whether self-reported family history can be used for risk assessment concerning hormone and surgery /cast related VTE in women. PATIENTS/METHODS: 1288 women 18-64 years with a first event of VTE and 1327 age-matched controls were included in a nation-wide population-based case-control study in Sweden. Odds ratios were calculated by comparing occurrence of VTE in women with and without a positive family history in combination with hormones or surgery/cast. RESULTS: The risk of hormone-associated VTE was doubled in women with a family history of VTE as compared to women with hormones and negative family history. The risk was more than tripled in women with surgery/cast and a positive family history, as compared to surgery/cast patients with negative family history. Women with a positive family history and combined hormonal contraceptive or menopause hormone treatment had an OR of 15.3 (95% CI 6.1-38) and 5.9 (95% CI 3.3-11) respectively compared to women without hormones or family history. The corresponding OR in women with surgery/cast and a positive family history was 67 (95% CI 21-213) compared to women without surgery/cast treatment and a negative family history. CONCLUSION: Self-reported family history is associated with increased odds of developing VTE on combined hormonal contraceptives, menopause hormone treatment and in connection with surgery or plaster. We believe that assessing family history of VTE can be helpful in identifying high risk patients.

Obesity and thrombin-generation profiles in women with venous thromboembolism.

Obesity is a known risk factor for venous and arterial thrombosis but the mechanisms are still unclear. In women, obesity is correlated with low-grade inflammation and recent data show that BMI is positively associated with thrombin generation. We explored the correlations between obesity, inflammation and thrombin generation in women with increased thrombotic risk by looking at a cohort of women with prior venous thrombosis. One hundred and fifty-six women age 18-65 years were enrolled at diagnosis of first venous thromboembolism (VTE). Plasma samples were obtained at least 3 weeks after cessation of anticoagulant treatment. Thrombin generation was determined with the calibrated automated thrombography (CAT) assay and the Innovance ETP assay. Thrombin generation started later but was more pronounced with higher endogenous thrombin generation potential (ETP) determined with CAT in patients with obesity. The Innovance ETP assay showed results consistent with CAT. Furthermore, patients with obesity had significantly higher levels of fibrinogen, C-reactive protein and plasminogen activator inhibitor-I (PAI-I) than patients without obesity. Increased levels of fibrinogen were the main determinant of the prolonged lag-time in patients with obesity whereas higher levels of prothrombin could account for the difference in the ETP between the groups. We found an association between BMI and ETP values using two different methods to measure thrombin generation. Obesity correlated with increased thrombin generation in women with VTE and the main determinants of this hypercoagulable state were increased levels of fibrinogen and prothrombin. This shows a possible link between obesity, low-grade inflammation and increased thrombin generation in women at increased risk for future thrombosis.

Non-steroidal anti-inflammatory drugs and venous thromboembolism in women.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) might increase the risk of venous thromboembolism (VTE), and risks might differ by type of NSAID. Compared with men, women have a higher incidence of VTE at younger age, and they more often use NSAIDs. OBJECTIVES: To assess risks of VTE in young and middle-aged women in association with use of NSAIDs. PATIENTS/METHODS: In a nationwide case­control study (Thrombo Embolism Hormone Study) performed in Sweden 2003­2009, we included as cases 1433 women, 18 to 64 years of age with a first time VTE. Controls were 1402 randomly selected women, frequency matched by age. Information was obtained by telephone interviews and DNA analyses of blood samples. We calculated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) adjusting for degree of immobilization, chronic disease, smoking, body mass index, use of hormonal contraception, hormone therapy or other NSAIDs. RESULTS: Use of NSAIDs was not associated with increased risks of VTE (OR = 0.98, 95% CI 0.80­1.19). The OR was 0.88 for propionic acid derivatives (95% CI 0.72­1.10), 1.18 for acetic acid derivatives (95% CI 0.82­1.70) and 1.76 for coxibs (95% CI 0.73­4.27). For users of acetic acid derivatives and coxibs, the ORs increased by cumulative dose. Carriership of the prothrombin gene mutation or factor V Leiden had only minor effects on the results. CONCLUSIONS: We found no increased risks of VTE in association with use of NSAIDs. Users of high cumulative doses of acetic acid derivatives and coxibs had the highest risks, suggesting a relationship with cyclooxygenase selectivity and dose.

Risk factors for venous thromboembolism in pre-and postmenopausal women.

INTRODUCTION: Hemostasis in women is affected by changes of estrogen levels. The role of endogenous estrogens on risk of venous thromboembolism (VTE) remains unclear. The aim of this study was to investigate the importance of acquired and genetic risk factors for VTE in pre-and postmenopausal women. METHOD: In a nationwide case-control study we included as cases 1470 women, 18 to 64years of age with a first time VTE. The 1590 controls were randomly selected and matched by age to the cases. Information on risk factors was obtained by interviews and DNA-analyses. We used unconditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The ORs were generally of similar magnitude in pre- and postmenopausal women. The highest risk was for the combination of surgery and cast (adjusted OR 54.12, 95% CI 16.62-176.19) in postmenopausal women. The adjusted OR for use of menopausal hormone therapy was 3.73 (95% CI 1.86-7.50) in premenopausal and 2.22 (95% CI 1.54-3.19) in postmenopausal women. Overweight was linked to an increased risk and exercise to a decreased risk, regardless of menopausal status. CONCLUSION: Menopausal status had only minor influence on the risk levels. Acquired transient risk factors conveyed the highest risks for VTE.

Mild primary hyperparathyroidism: vitamin D deficiency and cardiovascular risk markers.

CONTEXT: The extent and clinical significance of cardiovascular (CV) abnormalities associated with mild primary hyperparathyroidism (PHPT) are still matters for discussion. OBJECTIVE: The main objective of the present study was to evaluate biochemical CV risk markers in PHPT patients before and after parathyroidectomy (PTX) in comparison with controls. DESIGN AND SUBJECTS: In a prospective case-control design, 49 patients with PHPT and 49 healthy matched controls were included. METHODS: Blood pressure (BP), 25-OH-D, plasminogen activator inhibitor-1 activity, von Willebrand factor antigen, homocysteine, high-sensitivity C-reactive protein, IGF-I, and lipid profile were evaluated at baseline and 15 ± 4 months after PTX. RESULTS: At baseline, the level of 25-OH-D was significantly lower in patients compared with controls (40.1 ± 16.5 vs. 64.6 ± 20.8 nmol/liter, P < 0.001) and increased after PTX (58.9 ± 19.5, P < 0.001). Postoperatively, 25-OH-D was inversely correlated to the PTH level (r = -0.34; P < 0.05). Systolic BP (127.2 ± 17.4 vs. 119.3 ± 12.5 mm Hg, P < 0.05) and triglyceride (TG; 1.04 ± 0.60 vs. 0.86 ± 0.43 mmol/liter, P < 0.05) were higher in patients compared with controls and decreased slightly in patients after PTX (BP, 124.4 ± 16.8 mm Hg, and TG, 0.94 ± 0.50 mmol/liter, P < 0.05). Otherwise, there were no intergroup differences in coagulation, inflammatory, metabolic, and lipid status. CONCLUSIONS: Except for a lower 25-OH-D level and slightly higher systolic BP and TG levels, patients with mild PHPT without other CV risk factors did not differ from healthy controls as regards biomarkers predicting CV diseases. PTX had an overall positive effect on TG level, BP, and vitamin D status.

Bleeding from gastrointestinal angioectasias is not related to bleeding disorders - a case control study.

BACKGROUND: Angioectasias in the gastrointestinal tract can be found in up to 3% of the population. They are typically asymptomatic but may sometimes result in severe bleeding. The reasons for why some patients bleed from their angioectasias are not fully understood but it has been reported that it may be explained by an acquired von Willebrand syndrome (AVWS). This condition has similar laboratory findings to congenital von Willebrand disease with selective loss of large von Willebrand multimers. The aim of this study was to find out if AVWS or any other bleeding disorder was more common in patients with bleeding from angioectasias than in a control group. METHODS: We compared bleeding tests and coagulation parameters, including von Willebrand multimers, from a group of 23 patients with anemia caused by bleeding from angioectasias, with the results from a control group lacking angioectasias. RESULTS: No significant differences between the two groups were found in coagulation parameters, bleeding time or von Willebrand multimer levels. CONCLUSION: These results do not support a need for routine bleeding tests in cases of bleeding from angioectasias and do not show an overall increased risk of AVWS among these patients.

A follow-up study of the fate of small asymptomatic deep venous thromboses.

BACKGROUND: Postoperative asymptomatic deep venous thromboses (ADVT) can give rise to posttthrombotic syndrome (PTS), but there are still many unresolved issues in this context. For example, there is a lack of knowledge regarding the fate of small ADVT following minor orthopedic surgery. This follow-up study evaluates postthrombotic changes and clinical manifestations of PTS in a group of patients with asymptomatic calf vein DVT after surgery for Achilles tendon rupture. METHODS: Forty-six consecutive patients with distal ADVT were contacted and enrolled in a follow-up consisting of a single visit at the hospital at a mean time of 5 years postoperatively, including clinical examination and scoring, ultrasonography and venous plethysmography. All patients had participated in DVT-screening with colour duplex ultrasound (CDU) 3 and 6 weeks postoperatively and 80% of them were treated with anticoagulation. RESULTS: With CDU postthrombotic changes and deep venous reflux were detected at follow-up in more than 50% of the patients, more commonly in somewhat larger calf DVT:s initially affecting more than one vessel. However, only about 10% of the patients had significant venous reflux according to venous plethysmography. No patient had plethysmographic evidence of remaining outflow obstruction, but presence of postthrombotic changes shown with CDU negatively influenced venous outflow capacity measured with plethysmography. A clinical entity of PTS was rarely found and occurred only in two patients (4%) and then classified by Villalta scoring as of mild degree with few clinical signs of disease. Distal ADVT:s detected in the early postoperative period (3 weeks) showed DVT-progression in 75% of the limbs that were still immobilized and without anticoagulation. CONCLUSIONS: Asymptomatic postoperative distal DVT:s following surgery for Achilles tendon rupture have a good prognosis and a favourable clinical outcome. In our material of 46 patients the general appearance of the clinical entity of PTS at 5 years follow-up was low (<5%). Morphological and functional abnormalities were mainly seen in those patients that initially had somewhat larger distal DVT:s involving more than one deep calf vein segment.

The use of D-dimer testing and Wells score in patients with high probability for acute pulmonary embolism.

RATIONALE, AIMS AND OBJECTIVE: To investigate if a combination of Wells pre-test probability score and D-dimer testing could be used as a safe base for making clinical decisions on further investigations for patients with intermediate to high risks of pulmonary embolism (PE). METHODS: One hundred and twenty patients with signs or symptoms of acute PE were investigated with pulmonary angiography (PA) or contrast enhanced computed tomography of the pulmonary arteries (CTPA), D-dimer testing (Tinaquant) and clinical scoring using the Wells pre-test probability score during their first 48 hours at the hospital. Patients were recruited consecutively from emergency departments at two teaching hospitals. RESULTS: The cut-off value of 0.5 mg L(-1) in D-dimer analysis is proved adequate with a negative predictive value (NPV) of 92% in this group of patients with intermediate to high risks. The combination of D-dimer testing and Wells score increases the NPV to 94%. The specificities of both tests were low. CONCLUSION: D-dimer and Wells pre-test probability scores are safe to rule out acute PE even in patients with at least an intermediate risk of PE, but the specificity is low. D-dimer testing had a higher NPV than Wells score and the combination improved the algorithm further. The cut-off level for a high risk of PE measured with the Wells score was four and it seems reasonable to use that cut-off level in future algorithms. In addition, both PA and CTPA can present false positive and negative results difficult to interpret.

Evaluation of Wells score and repeated D-dimer in diagnosing venous thromboembolism.

BACKGROUND: Patients presenting with symptoms suggestive of venous thromboembolism (VTE), i.e., deep vein thrombosis (DVT) and pulmonary embolism (PE), are common at the emergency departments. However, of those, only 15-25% actually have the disease. The aims of this study were to determine (1) if low pre-test probability (PTP) using the Wells score, together with a normal D-dimer, safely excludes VTE in outpatients and (2) if a follow-up D-dimer adds extra information. METHODS: Patients (n=151, 68% women) with suspected VTE, a PTP below 1.5, and a D-dimer test (TinaQuant) below 0.5 mg/L were included in the study and underwent no further diagnostic investigations. Patients (n=177, 54% women) with D-dimer levels of 0.5 mg/L or higher or a PTP of 1.5 or higher were excluded. A follow-up D-dimer test was conducted 3-7 days after the initial hospital visit and further diagnostic investigations were made if test results were abnormal. Patients were studied for 3 months. RESULTS: A follow-up D-dimer test was conducted in 101/151 cases (67%), 13/101 of which revealed elevated D-dimer levels. None of these 13 patients had persistent symptoms or was diagnosed with VTE. All 151 patients were contacted after 3 months; none of them had clinical signs of VTE. Of the 177 patients excluded, 45 (25%) were diagnosed with VTE. Of the 176/328 (151+177) patients with normal D-dimer levels, only 1 had VTE (<0.01%). CONCLUSION: A normal PTP using the Wells score and a normal D-dimer safely excludes VTE at the emergency department. A follow-up D-dimer test adds no further information.