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Background: Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulants for the treatment and prophylaxis of venous thromboembolism in pregnancy. Hypersensitivity skin reactions associated with the use of LMWH are frequently seen, but are probably underreported., Objective: To evaluate the incidence of hypersensitivity skin reactions due to the use of LMWH in pregnancy, and the subsequent management of anticoagulation., Patients/methods: From 1999 to 2009, we followed consecutive women who used therapeutic anticoagulation for venous indications. Women visited a combined obstetric/coagulation clinic and were seen by a thrombosis specialist every two months until six weeks postpartum. All women were started on nadroparin., Results: We included 135 pregnancies in 88 women. Overall, in 52 of 135 pregnancies (39%), women switched at least once to another anticoagulant because of the development of hypersensitivity skin reactions. Switching to another preparation of LMWH was effective in 77% of the cases. In 23% of the cases skin reactions recurred and another switch had to be made., Conclusion: In almost half of the pregnancies, women had to switch at least once to another anticoagulant preparation due to the development of hypersensitivity skin reactions on LMWH. In most cases, skin reactions did not recur on the second preparation of LMWH used.

Background: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity., Objective: We aimed to investigate whether insulin resistance is a risk factor for VTE., Methods: For this analysis we used the PREVEND prospective community-based observational cohort study. Insulin resistance was measured as HOMA-IR (homeostasis model assessment of insulin resistance) and fasting insulin. VTE was assessed using databases of the national registries of hospital discharge diagnoses, death certificates and the regional anticoagulation clinic., Results: Out of 7393 subjects, 114 developed VTE during a median follow-up of 10.5 years. High HOMA-IR was associated with increased risk of VTE after adjustment for traditional cardiovascular risk factors, CRP and markers of endothelial dysfunction (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 1.09-1.75; P=0.007). When body mass index (BMI) was added to the model, BMI was a strong risk predictor for VTE (HR, 1.53; 95% CI, 1.24-1.88; P<0.001) whereas HOMA-IR no longer showed such an association (HR, 1.11; 95% CI, 0.85-1.43; P=0.45). Results were similar for fasting insulin., Conclusion: Our population-based cohort study shows an increased risk of VTE in subjects with increasing insulin resistance but not independently of BMI., (© 2012 International Society on Thrombosis and Haemostasis.)

We determined in a prospective cohort of patients treated with vitamin K antagonists for venous thrombosis, the course of factor VIII (FVIII:C), C-reactive protein (CRP) and fibrinogen levels, to assess the influence of the acute phase reaction on FVIII:C levels. Second, we hypothesized that patients with preceding infectious symptoms might have higher levels of FVIII:C at baseline than patients without those. We included 75 patients. Blood was sampled at baseline, once during treatment (t=1) and at the end of treatment (t=2). Mean levels of FVIII:C were 207, 186 and 175IU/dL (p for trend 0.003) at baseline, t=1 and t=2 respectively. Eight-eight percent of patients had an elevated FVIII:C at baseline, 75% at t=1 and 72% at t=2 (p for trend 0.045). Mean levels of FVIII:C were not different in patients with or without preceding infectious symptoms (206 versus 205IU/dL respectively). A baseline CRP level below 62mg/L could best distinguish between patients who will keep an elevated FVIII:C and those who will drop below 150IU/dL. We conclude that FVIII:C levels are partially influenced by the acute phase reaction, especially in patients who keep a persistent elevated FVIII:C during treatment. Preceding infectious symptoms did not influence baseline FVIII:C levels., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We consider the joint modelling of longitudinal and event time data. The longitudinal data are irregularly collected and the event times are subject to right censoring. Most methods described in the literature are quite complex and do not belong to the standard statistical tools. We propose a more practical approach using Cox regression with time-dependent covariates. Since the longitudinal data are observed irregularly, we have to account for differences in observation frequency between individual patients. Therefore, the time elapsed since last observation (TEL) is added to the model. TEL and its interaction with the time-dependent covariate show a strong effect on the hazard. The latter indicates that older recordings have less impact than recent recordings. Pros and cons of this methodology are discussed and a simulation study is performed to study the effect of TEL on the hazard. The fitted Cox model serves as a starting point for the prediction of future patient's events. Our method is applied to a study on chronic myeloid leukaemia (CML) with longitudinal white blood cell counts (WBC) as time-dependent covariate and patient's death as event., (Copyright 2001 John Wiley & Sons, Ltd.)

Background: There is no consistent definition at what age patients with non-Hodgkin lymphoma (NHL) are considered "elderly." This might hamper well balanced decisions with respect to treatment., Methods: From a population-based NHL registry the age groups younger than 60 years, 60-64 years, 65-69 years, 70-74 years, and 75 years and older were analyzed in relation to the revised European-American lymphoma classification and to the age-adjusted International Prognostic Index (IPI). The prognostic value of the variables from the age-adjusted IPI was determined. The relative survival probabilities were calculated., Results: The incidence of diffuse large B-cell lymphoma (DLBL) increased with advancing age, as was the case for small lymphocytic lymphomas. Follicular lymphomas were less frequently encountered with advancing age. With respect to the so-called indolent lymphomas, a decreasing complete remission rate and overall survival rate (5-year) was observed for patients older than 70 years, whereas patients with DLBL fared worse when older than 65 years and 60 years, respectively. The age-adjusted IPI score was discriminative for prognosis. However, even with an IPI score nil, the age group older than 75 years fared significantly worse (P < 0.009), but less so with the relative survival model. The relative survival at 5 years was 60%, 53%, 48%, 35%, and 32% for the 5 respective age groups., Conclusions: Patients with indolent lymphomas become elderly when they are older than 70 years, but when aggressive lymphoma is concerned this occurs when patients are older than 65 years. For patients with an IPI score nil, age older than 75 years is the dominant prognostic factor. The negative influence of concomitant disease on overall survival, although continuously increasing in older age groups, seems to diminish for patients older than 75 years when compared with the general Dutch population., (Copyright 2000 American Cancer Society.)

Background: Primary extranodal lymphomas (EN-NHLs) are a heterogeneous category of tumors that are considered to be different from primary nodal non-Hodgkin's lymphomas (N-NHLs). To what extent these differences have clinical implications is currently not very clear, because knowledge of EN-NHL as a separate group is limited., Methods: Using data from the Comprehensive Cancer Centre West (CCCW) population-based NHL registry in the Netherlands, N-NHL and EN-NHL patients were compared to determine differences in characteristics at diagnosis, responses to treatment, patterns of failure, and survival., Results: At presentation, EN-NHL patients had poorer performance scores and more often bulky tumors compared with N-NHL patients, resulting in poorer responses to treatment (complete response rates were 72% and 84%, respectively; P=0.04) and inferior 5-year overall survival (49% and 63%, respectively; P=0.003). Among EN-NHL patients, considerable variations in response, survival, and relapse rates were observed, with gastric NHL patients having the best and central nervous system NHL patients having the worst prognosis (66% and 7% 5-year overall survival, respectively). Relapse rates for N-NHL and EN-NHL patients did not differ (39% and 36% 5-year relapse rates, respectively), whereas among EN-NHL patients considerable differences in relapse rates were noted. Relapses among N-NHL patients were mainly found in nodal sites, whereas recurrent disease in EN-NHL patients was mainly found in extranodal sites., Conclusions: In this population-based study, Stage I EN-NHL patients as a group had a poorer prognosis than N-NHL patients. However, among EN-NHL patients, considerable differences in response, relapse risk, and survival were observed. The failure analysis conducted in this study suggests that patterns of dissemination for N-NHL and EN-NHL are different.