Nationwide claims data validated for quality assessments in acute myocardial infarction in the Netherlands.

INTRODUCTION: Since health insurance is compulsory in the Netherlands, the centrally registered medical claims data might pose a unique opportunity to evaluate quality of (cardiac) care on a national level without additional collection of data. However, validation of these claims data has not yet been assessed. DESIGN: Retrospective cohort study. METHODS: National claims data ('national registry') were compared with data collected by patient records reviews in four representative hospitals ('validation registry'). In both registries, we extracted the national diagnosis codes for ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction of 2012 and 2013. Additionally, data on medication use at one year after acute myocardial infarction (AMI) was extracted from the Dutch pharmacy information systems and also validated by local patient records reviews. The data were compared at three stages: 1) validation of diagnosis and treatment coding; 2) validation of the hospital where follow-up has taken place; 3) validation of follow-up medical treatment after 365 days. RESULTS: In total, 3,980 patients ('national registry') and 4,014 patients ('validation registry') were compared at baseline. After one-year follow-up, 2,776 and 2,701 patients, respectively, were evaluated. Baseline characteristics, diagnosis and individual medication were comparable between the two registries. Of all 52,672 AMI patients in the Netherlands in 2012 and 2013, 81% used aspirin, 76% used P2Y12 inhibitors, 85% used statins, 82% used beta-blockers and 74% angiotensin converting enzyme inhibitors/angiotensin II antagonists. Optimal medical treatment was achieved in 49% of the patients with AMI. CONCLUSION: Nationwide routinely collected claims data in patients with an acute myocardial infarction are highly accurate. This offers an opportunity for use in quality assessments of cardiac care.

Patients who underwent total hip or knee arthroplasty are more physically active than the general Dutch population.

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) bring relief of pain and functional disability to patients with end-stage osteoarthritis, and however, the literature on their impact on patients' level of physical activity (PA) is scarce. Cross-sectional study in patients who underwent THA/TKA surgery in the preceding 6-22 months and a random sample of persons aged >40 years from the Dutch general population, participating in a national survey. PA in minutes per week (min/week) and adherence to the Dutch recommendation for PA (NNGB yes/no) were measured by the short questionnaire to assess health-enhancing PA. Multivariable linear (total min/week) and logistic regression analyses (meeting recommendations PA), adjusting for confounders, were performed for THA and TKA separately. In total, 258 THA [62.3% female, aged 69.4 (9.1)] and 221 TKA [65.7% female, aged 69.5 (8.9)] patients and 4373 persons from the Dutch general population [51.4% female, aged 58.9 (11.6)] were included. The presence of THA was associated after adjusting for age, sex, BMI education and musculoskeletal comorbidities, with more total min/week spent on PA (THA 13.8% increase, 95% CI 1.6-27.6%), whilst both TJA groups were associated with adhering to NNGB (THA: OR 1.79, 95% CI 1.26-2.56; TKA: OR 1.73, 95% CI 1.20-2.51). As this study used questionnaires to compare the PA of THA/TKA patients to the general population, some recall and selection bias might have been induced. After surgery, overall, TJA patients are more likely to adhere NNGB than a representative sample of persons >40 years from the Dutch general population.

Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: a retrospective survey.

Pregnant women with bleeding disorders require specialised peripartum care to prevent postpartum haemorrhage (PPH). If third trimester coagulation factor levels are <0.50 IU mL(-1) , prophylactic treatment is indicated and administered according to international guidelines. However, optimal dose and duration are unknown and bleeding may still occur. The aim of this study was to investigate the outcome in women with von Willebrand disease (VWD) or haemophilia carriership treated according to current practice guidelines. From the period 2002-2011, 185 deliveries in 154 VWD women or haemophilia carriers were retrospectively included. Data on blood loss, bleeding disorder characteristics and obstetric risk factors were obtained. The outcome was primary PPH, defined as blood loss ≥500 mL within 24 h postpartum and severe PPH as blood loss ≥1000 mL. Primary PPH was observed in 62 deliveries (34%), 14 (8%) of which resulted in severe PPH. In 26 deliveries prophylactic treatment was administered due to factor levels below the 0.50 IU mL(-1) cut-off in the third trimester, 14 of which (54%) were complicated by PPH. We found an increased PPH risk in deliveries given prophylactic treatment compared with deliveries without (OR 2.7, 95% CI 1.2-6.3). In conclusion, PPH incidence was highest in deliveries with the lowest factor levels in the third trimester. Currently, delivery outcome in women with bleeding disorders is unsatisfactory, given the high PPH incidence despite specialised care. Future studies are required to optimise management of deliveries in this patient population.

Prehospital use in emergency patients of a laryngeal mask airway by ambulance paramedics is a safe and effective alternative for endotracheal intubation.

BACKGROUND: In Dutch ambulance practice, failure or inability to intubate patients with altered oxygenation and/or ventilation leaves bag-valve mask ventilation as the only alternative, which is undesirable for patient outcome. A novel Laryngeal Mask Airway Supreme (LMA-S) device may be a suitable alternative. AIM: To evaluate the effectiveness and suitability of the LMA-S for emergency medical services in daily out-of-hospital emergency practice. METHODS: After a period of theoretical and practical training of ambulance paramedics in the use of the LMA-S, prospective data were collected on the utilisation of LMA-S in an observational study. Procedures for use were standardised and the evaluation included the number of direct intubation attempts before using LMA-S, attempts required, failure rate and the adequacy of ventilation. Data were analysed taking patient characteristics such as age and indication for ventilatory support into account. RESULTS: The LMA-S was used 50 times over a period of 9 months (33 involving cardiorespiratory arrest, 14 primary and three rescue). The LMA-S could be applied successfully in all 50 cases (100%) and was successful in the first attempt in 49 patients (98%). Respiratory parameters showed adequate oxygenation. All paramedics were unanimously positive about the utilisation of LMA-S because of the easiness of the effort of insertion and general use, and emphasised its value as a useful resource for patients in need. CONCLUSIONS: Ensuring ventilation support by using LMA-S by paramedics in prehospital emergency practice is safe and effective.

[When to suspect pulmonary embolism: a balancing act]. / Wanneer moet je aan een longembolie denken?

Pulmonary embolism (PE) is a common disease, which can present with a variety of symptoms. Optimal use of diagnostics is challenging given the tight and delicate balance between underdiagnosis and over-testing or overdiagnosis. Diagnostic delay occurs in a substantial part of patients, and seems more common in those with known cardiopulmonary disease or non-specific signs and symptoms. At the other end of the spectrum, the amount of diagnostic imaging increases. Increased use of diagnostic imaging in general leads to more harmful exposures and might result in overtreatment, as may be the case in subsegmental PE. Correct use of clinical prediction rules reduces the need for diagnostic imaging while PE can still be ruled out safely. This clinical lesson describes three cases of PE and provides an overview of factors that contribute to underdiagnosis or overdiagnosis. We provide recommendations to improve our balancing act for this challenging disease.

Venous and arterial thromboembolism after colorectal cancer in the Netherlands: Incidence, predictors, and prognosis.

BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer type. CRC-patients are at increased risk of venous and arterial thromboembolism (TE), but the magnitude of the risks, their predictors and consequences are not exactly known. OBJECTIVES: We aimed to determine incidence, predictors and prognosis of TE after incident CRC in a large, unselected population. METHODS: Using data from Statistics Netherlands and the Netherlands Comprehensive Cancer Organization, all incident CRC-patients were identified between 2013 and 2018 plus a sample of 1:2 age- and sex-matched control subjects. Incidence rates and cumulative incidences for TE were estimated. Predictor variables for TE were explored by univariable Cox regression. The association between TE and all-cause mortality was evaluated by multivariable time-dependent Cox regression. RESULTS: 68,238 incident CRC-patients were matched to 136,476 controls. CRC-patients had a 1-year cumulative venous TE (VTE) incidence of 1.93 % (95%CI 1.83-2.04), versus 0.24 % (95%CI 0.21-0.27) in controls (HR 8.85; 95%CI 7.83-9.99). For arterial TE (ATE), this was 2.74 % (95%CI 2.62-2.87) in CRC versus 1.88 % (95%CI 1.81-1.95) in controls (HR 1.57; 95%CI 1.47-1.66). Cancer stage, surgery, chemotherapy and asthma were predictors for VTE, whereas age, prior ATE and Parkinson's disease were predictors for ATE. CRC patients with TE had an increased risk of all-cause mortality (VTE HR; 3.68 (95%CI 3.30-4.10, ATE HR; 3.05 (95%CI 2.75-3.39)) compared with CRC-patients without TE. CONCLUSIONS: This Dutch nationwide cohort study adds detailed knowledge on the risk of VTE and ATE, their predictors and prognosis in CRC-patients. These findings may drive TE prophylactic management decisions.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Current clinical practice for thromboprophylaxis management in patients with Cushing's syndrome across reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN).

BACKGROUND: Cushing's syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. RESULTS: The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were 'medical history of VTE' (n = 15/23) and 'severity of hypercortisolism' (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported 'severe immobilization' as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included 'reduction of VTE risk' as a goal of treatment. CONCLUSIONS: There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.

Type-specific risk factors and outcome in an outbreak with 2 different Clostridium difficile types simultaneously in 1 hospital.

BACKGROUND: Clostridium difficile infection (CDI) due to polymerase chain reaction (PCR) ribotype 027 (type 027) has been described worldwide. In some countries, an increase was reported of toxin A-negative PCR ribotype 017 (type 017). We encountered an outbreak due to these 2 types occurring simultaneously in a 980-bed teaching hospital in the Netherlands. METHODS: In a case-control study from May 2005 through January 2007, we investigated general and type-specific risk factors as well as outcome parameters for CDI due to type 027 or 017. Clonal dissemination was investigated by multilocus variable number of tandem repeat analysis (MLVA). RESULTS: We identified 168 CDI patients: 57 (34%) with type 017, 46 (27%) with type 027, and 65 (39%) with 1 of 36 different other types. As controls, we included 77 non-CDI diarrheal patients and 162 patients without diarrhea. Risk factors for CDI were nasogastric intubation, recent hospitalization, and use of cephalosporins and clindamycin. Type-specific risk factors were older age for both types 017 and 027, use of clindamycin and immunosuppressive agents for type 017, and use of fluoroquinolones for type 027. At day 30 of follow-up, the overall mortality among patients with types 017, 027, other types, non-CDI diarrheal patients, and nondiarrheal patients was 23%, 26%, 3%, 2%, and 6%, respectively. MLVA showed persistent clonal dissemination of types 017 and 027, despite appropriate infection control measures. CONCLUSIONS: Patients with CDI have type-specific risk factors and mortality rates, with prolonged clonal spread of type 027 or 017.

Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.

INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease?

INTRODUCTION: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown. METHODS: In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared. RESULTS: We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score -8%, 95% confidence interval [95%CI] -16 to -0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; -30%, 95%CI -44% to -8.2). Moreover, the mean RV/LV ratio (mean difference -0.23, 95%CI -0.39 to -0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference -23%, 95%CI -41 to -0.86%) were lower in the COVID-19 patients. CONCLUSION: Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.

The association between leptin concentration and blood coagulation: Results from the NEO study.

BACKGROUND: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to what extent this association is influenced by total body fat. Therefore, we aimed to examine the association between serum leptin and blood coagulation while taking total body fat into account in a population-based cohort study. METHODS: We performed a cross-sectional analysis with baseline measurements of 5797 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort of middle-aged men and women. We examined associations between serum leptin concentration and coagulation factor concentrations and parameters of platelet activation in linear regression analyses. All analyses were adjusted for multiple covariates, including total body fat. RESULTS: In multivariable adjusted analyses a 1 µg/L higher serum leptin concentration was associated with a 0.22 IU/dL (95% CI: 0.11, 0.32) higher FVIII concentration and a 0.20 IU/dL (95% CI: 0.14, 0.27) higher FIX concentration (3.5 IU/dL FVIII and 3.2 IU/dL FIX per SD leptin). Serum leptin concentration was not associated with FXI, fibrinogen, platelet count, mean platelet volume and platelet distribution width in multivariable adjusted analyses. DISCUSSION: This study showed that serum leptin concentration was associated with higher concentrations of FVIII and FIX in an observational study, which could be clinically relevant.

Cardiovascular risk in young apparently healthy descendents from Asian Indian migrants in the Netherlands: the SHIVA study.

BACKGROUND.: Asian Indian migrants in the Western world are highly susceptible for ischaemic heart disease (IHD). Until now, most IHD risk studies were performed in first and second generation Asian Indian expatriates. For optimal prevention, knowledge of the cardiovascular risk profile of younger generations is crucial. METHOD.: In a cross-sectional study we assessed the prevalence of conventional IHD risk factors and Framingham risk score in asymptomatic third to seventh generation Asian Indian descendants, compared with Europeans. Subjects were classified as asymptomatic if they did not have documented IHD, diabetes, hypertension or high cholesterol. RESULTS.: A total of 1790 Asian Indians (45% men, age 35.9+/-10.7 years) and 370 native Dutch hospital employees (23% men, age 40.8+/-10.1 years) were recruited. Asian Indians had higher levels of total cholesterol, low-density lipoprotein, triglycerides, and lower high-density lipoprotein levels than the Dutch. Glucose intolerance was present in 7.1 vs. 0.5% men, and in 6.1 vs. 1.4% women (both p<0.001). Asian Indian women were more frequently obese (12 vs. 5%; p<0.001), and centrally obese (44 vs. 25%; p<0.001) as compared with the Dutch women. Prevalence of most of the conventional and modifiable cardiovascular risk factors in each ten-year age group was higher in Asian Indians compared with controls, which reflected in higher Framingham risk scores. CONCLUSION.: This study demonstrates the persistence of an unfavourable cardiovascular risk profile in young, third to seventh generation migrated Asian Indians and supports an aggressive screening and intervention strategy. (Neth Heart J 2009;17:155-61.).

Venous thromboembolism risk stratification for patients with lower limb trauma and cast or brace immobilization.

BACKGROUND: Thromboprophylaxis for patients with non-surgical isolated lower-limb trauma requiring immobilization is a matter of debate. Our aim was to develop and validate a clinical risk- stratification model based on Trauma, Immobilization and Patients' characteristics (the TIP score). METHODS: The TIP score criteria and the cut-off were selected by a consensus of international experts (n = 27) using the Delphi method. Retrospective validation was performed in a population-based case-control study (MEGA study). The potential score's impact in anticoagulant treatment was assessed in a prospective single-center observational cohort study. FINDINGS: After four successive rounds, 30 items constituting the TIP score were selected: thirteen items for trauma, three for immobilization and 14 for patient characteristics were selected, each rated on a scale of 1 to 3. In the validation database, the TIP score had an AUC of 0·77 (95% CI 0.70 to 0.85). Using the cut-off proposed by the experts (≥5) and assuming a prevalence of 1·8%, the TIP scores had a sensitivity, specificity and negative predictive values of 89·9%, 30·7% and 99·4% respectively. In the prospective cohort, 84·2% (165/196) of all the patients concerned who presented at the emergency department had a low VTE risk not requiring thromboprophylaxis according to their TIP scores. The 3-month rate of symptomatic VTE was 1/196 [95% CI 0.1-2.8] this patient was in the sub-group TIP score ≥5. CONCLUSION: For patients with non-surgical lower-limb trauma and orthopedic immobilization, the TIP score allows an individual VTE risk-assessment and shows promising results in guiding thromboprophylaxis.

High levels of coagulation factors and venous thrombosis risk: strongest association for factor VIII and von Willebrand factor.

Essentials Elevated procoagulant levels are associated with an increased risk of venous thrombosis (VT). The dependency on concurrent increased factor levels and VT was analyzed in a large study. Factor VIII (FVIII) and von Willebrand factor (VWF) were associated with the highest VT risk. The risks for other procoagulant factor levels were largely explained by FVIII and VWF. SUMMARY: Background Coagulation factors are essential for robust clot formation. However, elevated levels of procoagulant factors are associated with an increased risk of venous thrombosis (VT). The precise contribution of these factors to the development of VT is not yet understood. Objectives We determined the thrombosis risk for the highest levels of eight selected coagulation factors. Furthermore, we analyzed which of these coagulation factors had the strongest impact on the supposed association. Methods We used data of 2377 patients with a first VT and 2940 control subjects in whom fibrinogen, von Willebrand factor (VWF), factor II, FVII, FVIII, FIX, FX and FXI levels were measured. Results The odds ratios (ORs) for the various coagulation factor levels (> 99th percentile versus ≤ 25th percentile) varied between 1.8 and 4, except for FVIII (OR 23.0; 95% confidence interval [CI] 14.7-36.0) and VWF (OR 24.0; 95% CI 15.3-37.3). Adjustment for FVIII and VWF in a mediation analysis reduced the risks of the other factors to unity, with the exception of FIX and FXI (remaining ORs between 1.7 and 1.9). Conversely, the ORs for FVIII and VWF levels remained high after adjustment for all other procoagulant factors (FVIII: 16.0; 95% CI 9.7-26.3; VWF: 17.6; 95% CI 10.7-28.8). Conclusions Our results imply that the observed relationship between VT and coagulation factor levels can be largely explained by FVIII and VWF. FVIII and VWF levels were also associated with the highest VT risk.

The influence of thyroid function on the coagulation system and its clinical consequences.

Several studies indicate that low plasma levels of thyroid hormone shift the hemostatic system towards a hypocoagulable and hyperfibrinolytic state, whereas high levels of thyroid hormone lead to more coagulation and less fibrinolysis. Low levels of thyroid hormone thereby seem to lead to an increased bleeding risk, whereas high levels, by contrast, increase the risk of venous thromboembolism. Hypothyroidism leads to a higher incidence of acquired von Willebrand's syndrome and with increasing levels of free thyroxine, levels of fibrinogen, factor VIII and von Willebrand factor, amongst others, increase gradually, to the extent that they may lead to symptomatic venous thromboembolism in patients with hyperthyroidism. Here, we discuss the literature on the effect of thyroid hormone on the hemostatic system and the associated risk of bleeding and venous thromboembolism. Patients with hypothyroidism are at increased risk of developing bleeding complications, which could be relevant in patients undergoing invasive procedures. Furthermore, physicians should be aware of the possibility of hyperthyroidism as an underlying risk factor for venous thromboembolism, especially in unexplained cases. Clinical studies are needed to further investigate the significance for general practice of these findings. Besides the effects of hyperthyroidism on venous thromboembolism, its effects on embolism secondary to atrial fibrillation are described.

High risk of recurrent venous thrombosis in patients with lower-leg cast immobilization.

Essentials The risk of recurrent venous thrombosis (VT) after leg-cast in patients with prior VT is unknown. In a nested case-control study within the MEGA follow-up study we aimed to estimate this risk. Patients with a history of VT who require lower-leg cast have a 4.5-fold risk for recurrence. This relative risk translates to an absolute risk for recurrent VT of about 3.2% within 3 months. SUMMARY: Background Patients with lower-leg cast immobilization have a substantially increased risk of developing a first venous thrombosis (VT), whereas the risk in patients with a history of VT is as yet unknown. Aims To estimate the risk of recurrent VT after lower-leg cast immobilization in patients with a history of VT. Methods A case-control study nested within a cohort of 4597 patients with a first VT who were followed over time for recurrence from 1999 to 2010 (MEGA follow-up study). Participants completed a questionnaire on risk factors for recurrent thrombosis, including having a cast in the first 3 months before a recurrence (cases) or a random 3-month period during follow-up for participants without recurrence (controls). In total, 2723/4597 (59%) participants returned the questionnaire. Odds ratios (ORs), adjusted for age and sex, were calculated to compare risks of recurrence between subjects with and without a cast. Results A total of 2525/2723 participants (93%) filled out information on cast immobilization and were included in the analysis (451 cases; 2074 controls). Twenty (1.0%) controls and 10 (2.2%) cases reported having had a lower-leg cast in the 3 months before the control or recurrence date (adjusted OR, 2.4; 95% confidence Interval [CI], 1.1-5.3). We cross-checked the data with these patients' medical records. Cast application within 3 months was verified in seven (0.3%) controls vs. six (1.3%) cases, leading to an adjusted OR of 4.5 (95% CI, 1.5-14.0) and corresponding cumulative incidence of 3.2%. Conclusions Lower-leg cast immobilization increases the risk of recurrent VT in the 3 months after its application in patients with a history of VT.

Mild antithrombin deficiency and risk of recurrent venous thromboembolism: results from the MEGA follow-up study.

Essentials Mild antithrombin deficiency may increase the risk of recurrent venous thromboembolism (VTE). In a cohort study, we stratified patients with VTE to various cut-off antithrombin levels. A 1.6-3.7-fold increased risk of recurrent VTE was observed in the lowest antithrombin categories. Mild antithrombin deficiency (activity < 5th percentile of normal) increases recurrent VTE risk. SUMMARY: Background Mild antithrombin deficiency (previously defined as antithrombin activity below 70% or 80%) has been associated with a 2.4-3.5-fold increased risk of recurrent venous thromboembolism (VTE). This finding may have implications for duration of antithrombotic therapy in VTE patients with mild antithrombin deficiency. Objectives To externally validate whether mild antithrombin deficiency is a risk factor for recurrent VTE. Methods In a population-based cohort study, patients with a first VTE (n = 2357) were stratified according to percentile cut-off antithrombin levels (< 5th [< 87%], 5-10th [87-92%], > 10th percentile [> 92%]) and functional antithrombin levels (< 70%, 70-80%, > 80%). Results During a median follow-up of 7.4 years, 361 recurrent events occurred (incidence rate, 2.5/100 patient-years). We observed an increased risk of recurrent VTE in the lowest antithrombin activity category (< 5th percentile; < 87%) as compared with antithrombin activity that was > 10th percentile (> 92%), with an adjusted hazard ratio (HR) of 1.5 (95%CI, 1.0-2.3). When analyses were stratified to antithrombin cut-off criteria of< 70% vs. patients with antithrombin activity > 80%, the adjusted HR for venous recurrence was 3.7 (95% CI, 1.4-9.9). Mild antithrombin deficiency was able to predict recurrent VTE over at least 8 years of follow-up and the association remained present when the population was stratified to the presence or absence of thrombosis risk factors. Restriction analyses, where patients who used anticoagulation at time of blood draw and those who reported drinking ≥ 5 glasses alcohol daily were excluded, did not materially affect these outcomes. Conclusion This study confirms that mild antithrombin deficiency is a risk factor for recurrent VTE.

Cancer and risk of cerebral venous thrombosis: a case-control study.

Essentials The risk of cerebral venous thrombosis (CVT) in patients with cancer is not known. We performed a case-control study including 594 patients with CVT and 6278 controls. History of cancer increased the risk of CVT approximately 5-fold. The association was strongest with hematological cancer in the first year after diagnosis. SUMMARY: Background Cancer is an established risk factor for leg vein thrombosis and pulmonary embolism. Controlled studies assessing the risk of cerebral venous thrombosis (CVT) in patients with cancer have not been performed. Objective To assess whether cancer is a risk factor for CVT. Patients/Methods This was a case-control study. We assessed consecutive adult patients with CVT from three academic hospitals from 1987 to 2015, and control subjects from the Dutch MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). We adjusted for age, sex and oral contraceptive use, and stratified for type of cancer and time since diagnosis of cancer. Results We included 594 cases and 6278 controls. In total, 53 cases (8.9%) and 160 controls (2.5%) had a history of cancer. Cases were younger (median 42 vs. 48 years), more often female (68% vs. 54%) and more often used oral contraceptives (55% vs. 23%) than controls. The risk of CVT was increased in patients with cancer compared with those without cancer (adjusted odds ratio [aOR], 4.86; 95% confidence interval [CI], 3.46-6.81). Patients with a hematological type of cancer had a higher risk of CVT (aOR, 25.14; 95% CI, 11.64-54.30) than those with a solid type of cancer (aOR, 3.07; 95% CI, 2.03-4.65). The association was strongest in the first year after diagnosis of cancer (hematological aOR, 85.57; 95% CI, 19.70-371.69; solid aOR, 10.50; 95% CI, 5.40-20.42). Conclusions Our study indicates that cancer is a strong risk factor for CVT, particularly within the first year of diagnosis and in patients with a hematological type of cancer.