Determining the minimal clinically important difference for the PEmbQoL questionnaire, a measure of pulmonary embolism-specific quality of life.

Essentials The minimal clinically important difference (MCID) for PEmbQoL has not yet been determined. We estimated the MCID for PEmbQoL and its subscales via anchor- and distribution-based approaches. Our results indicate that MCID for PEmbQoL appears to be 15 points. Our work enables interpretation of changes or differences in PEmbQoL. SUMMARY: Background Pulmonary embolism (PE) reduces quality of life (QOL). The PEmbQoL questionnaire, a PE-related QOL measure, was recently developed and validated and has been used to quantify disease-specific QOL in clinical studies of patients with PE. However, to date, interpretation of PEmbQoL scores has been limited by a lack of information on the minimal clinically important difference (MCID) of this measure. Objective To determine the MCID for PEmbQoL and its subscales using anchor-based and distribution-based approaches. Methods We analyzed data from the ELOPE Study, a prospective, multicenter cohort study of long-term outcomes after a first episode of acute PE. At baseline and 1, 3, 6 and 12 months after PE, we measured generic QOL (SF-36), PE-specific QOL (PEmbQoL) and dyspnea severity (UCSD Shortness of Breath Questionnaire). We used time-varying repeated-measures mixed-effect models to estimate anchor-based MCID and effect sizes to estimate distribution-based MCID. Results Eighty-two patients participated in this sub-study. Their mean age was 49.4 years, 60% were male and 84% had PE diagnosed in an outpatient setting. Using both anchor- and distribution-based approaches, the MCID for PEmbQoL appears to be 15 points. Based on this MCID, 42%, 59%, 66% and 75% of patients experienced at least one MCID unit of improvement in PEmbQoL from baseline to 1, 3, 6 and 12 months, respectively. Conclusion Our results provide new information on the MCID of PEmbQoL, a PE-specific QOL questionnaire that can be used by researchers and clinicians to measure and interpret changes in PE-specific QOL over time, or as an outcome in clinical trials.

Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood.

Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy.

BACKGROUND: Although women with antiphospholipid antibodies (APLAs) are at increased risk of recurrent miscarriage, the outcome of a subsequent pregnancy is not clearly elucidated. OBJECTIVES: To assess the pregnancy outcome of a subsequent pregnancy in women with APLAs and compare this outcome with women with unexplained recurrent miscarriage. METHODS: We performed a cohort study among all women who attended the Miscarriage Clinic at Liverpool Women's Hospital between 1987 and 2006 after being referred due to recurrent miscarriage (≥2 consecutive pregnancy losses). All women underwent a standardized investigation sequence. Women with other reasons for recurrent miscarriage were excluded. RESULTS: A total of 693 women fulfilled the selection criteria, of whom 176 (25%) had APLAs. One hundred and twenty-two (69%) women with APLAs had a subsequent live birth compared with 324 (63%) women with unexplained recurrent miscarriage (OR 1.3, 95% CI 0.9-1.9). No differences were found for birth weight, gestational age, and intra-uterine growth restriction. When treatment was analyzed, 53/67 (79%) of women with APLAs who had received aspirin and heparin during their pregnancy had a live birth, compared with 64/104 (62%) of women with APLAs who received aspirin only (adjusted OR 2.7, 95% CI 1.3-5.8). In unexplained recurrent miscarriage, stratification for treatment showed no differences in outcome. CONCLUSION: The prognosis of a subsequent pregnancy in women with APLAs is good. Although this was not a randomized clinical trial, combined treatment of aspirin and heparin seemed associated with a better outcome in women with APLAs, but not in women with unexplained recurrent miscarriage.

Increased sperm count may account for high population frequency of factor V Leiden.

BACKGROUND: Factor V Leiden (FVL) increases the risk of venous thrombosis and pregnancy loss in carriers. Nevertheless, this relatively old mutation is prevalent in Caucasion populations, which could be explained by positive selection pressure. Men with FVL have previously been found to have higher fecundity (the time between marriage and first pregnancy). Whether this is caused by increased sperm counts in men with FVL is unknown. OBJECTIVES: To assess whether men with factor V Leiden have increased sperm counts. PATIENTS/METHODS: We performed a prospective cohort study among 1139 consecutively included male partners of subfertile couples presenting at our university hospital for fertility workup between January 2000 and July 2007. All potential candidates who gave informed consent were included, irrespective of their fertility workup. In this retrospective analysis, we excluded participants with known causes of spermatogenic function or azoospermia. Subsequently, we genotyped all participants and compared sperm counts between FVL carriers and non-carriers. RESULTS: We identified 37 FVL carriers and 921 non-carriers. FVL carriers had higher total sperm counts and total motile sperm counts than non-carriers: 236 x 10(6) (95% CI 158-292 x 10(6)) vs. 163 x 10(6) (95% CI 147-178 x 10(6)) and 81 x 10(6) (95% CI 54-105 x 10(6)) vs. 52 x 10(6) (95% CI 48-57 x 10(6)), respectively. CONCLUSIONS: To our knowledge, this is the first study that indicates that an increased incidence of a genotype may be controlled by increased sperm counts. However, the finding that men with FVL had higher total (motile) sperm counts was not statistically significant and needs confirmation in other studies.

Quality of life after pulmonary embolism: validation of the PEmb-QoL Questionnaire.

BACKGROUND: Even though quality of life (QoL) has become a key component of medical care, there is no instrument available that specifically measures QoL after pulmonary embolism (PE). Recently, the Pulmonary Embolism Quality of Life (PEmb-QoL) Questionnaire has been developed to address this gap. OBJECTIVE: To evaluate the validity of the PEmb-QoL questionnaire. METHODS: We distributed the PEmb-QoL questionnaire and the Short Form-36 (SF-36) questionnaire twice among consecutive subjects with a history of objectively confirmed acute PE. Internal consistency reliability, test-retest reliability, convergent validity and criterion validity, and correlations between the PEmb-QoL and clinical patient characteristics were assessed using standard-scale construction techniques. RESULTS: Ninety participants completed the questionnaires twice. Internal consistency was adequate (Cronbach's alpha 0.62-0.94), as well as test-retest reliability (intra-class correlation coefficients: 0.78-0.94). Furthermore, correlation between the PEmb-QoL questionnaire and the SF-36 questionnaire supported convergent validity. Age, obesity, cardiopulmonary comorbidity, centrally located PE and a family history of venous thromboembolism were shown to be independent determinants of disease-specific QoL. CONCLUSION: The PEmb-QoL questionnaire is a reliable instrument to specifically assess QoL following PE, which is helpful in the identification of patients with decreased QoL following acute PE.

Venous thrombosis is associated with hyperglycemia at diagnosis: a case-control study.

BACKGROUND: Patients with (undiagnosed) diabetes mellitus, impaired glucose tolerance or stress-induced hyperglycemia may be at greater risk for venous thrombosis and present with relative hyperglycemia during the thrombotic event. OBJECTIVES: To assess whether venous thrombosis is associated with hyperglycemia at diagnosis. PATIENTS/METHODS: We performed a case-control study, derived from a cohort of consecutive patients referred for suspected deep vein thrombosis. Cases were patients with confirmed symptomatic venous thrombosis of the lower extremity. Controls were randomly selected in a 1 : 2 ratio from individuals in whom this diagnosis was excluded. We measured plasma glucose levels upon presentation to the hospital. RESULTS: In total, 188 patients with thrombosis and 370 controls were studied. The glucose cut-off levels for the first to fourth quartiles were as follows: first quartile, < 5.3 mmol L(-1); second quartile, 5.3-5.7 mmol L(-1); third quartile, 5.7-6.6 mmol L(-1); and fourth quartile, >or= 6.6 mmol L(-1). When adjusted for body mass index, a known history of diabetes mellitus, age, sex, ethnicity and whether known risk factors for deep vein thrombosis were present, the odds ratios for deep vein thrombosis in the second, third and fourth quartiles of glucose levels as compared with the first quartile were 1.59 [95% confidence interval (CI) 0.89-2.85], 2.04 (95% CI 1.15-3.62) and 2.21 (95% CI 1.20-4.05), respectively; P for trend = 0.001. CONCLUSIONS: Increased glucose levels measured at presentation were associated with venous thrombosis. Experimental evidence supports a potential causal role for hyperglycemia in this process. As this is the first report on the association between (stress) hyperglycemia and venous thrombosis, confirmation in other studies is required.

[Early termination of the multicentre randomised clinical trial to evaluate the benefit of testing for thrombophilia following a first venous thromboembolism: the NOSTRADAMUS study]. / Vroegtijdige beëindiging van het onderzoek naar het nut van trombofilietests bij een eerste veneuze trombo-embolie: het NOSTRADAMUS-onderzoek.

The NOSTRADAMUS study (ISRCTN07836779) was prematurely terminated due to low inclusion rates. There were several causes for this low inclusion: delay of approval by medical ethics committees, competition with industry-initiated intervention studies with a higher financial compensation, and the lack of study staff and allowance of expenses. We advise restraint with respect to testing for thrombophilia in patients with a first deep vein thrombosis or pulmonary embolism, as the benefit of this procedure has yet to be demonstrated.

The psychological impact of testing for thrombophilia: a systematic review.

BACKGROUND: Nowadays, large numbers of patients are tested for thrombophilia, even though the benefits of this strategy remain unclear. A potential disadvantage of this predominantly genetic testing is the psychological impact, including fear, depression and worry. OBJECTIVES: To systematically review studies that determined the nature and extent of the psychological impact of testing for thrombophilia. PATIENTS/METHODS: We searched the MEDLINE data base (1966-2008), the EMBASE data base (1985-2008) and the PsychInfo data base (1806-2008) for relevant trials, without language restrictions. Bibliographies of relevant articles were scanned for additional articles. We reviewed all relevant studies that focused on the psychological impact of testing for thrombophilia. Only full papers of studies that included 15 patients or more were considered eligible for this review. Two reviewers independently extracted data and assessed quality. RESULTS: Six studies fulfilled the eligibility criteria. As these studies varied appreciably in methodology, the pooling of data was not possible. Studies of psychological impact of genetic testing for thrombophilia report few negative results, although most assessments were limited to short-term follow-up, or lacked methodological accuracy. CONCLUSIONS: No valid conclusions can be drawn about the psychological impact of genetic testing in patients based on the current available literature. Given the large number of patients that are being exposed to testing for thrombophilia, and the uncertain benefits, there is an urgent need for more uniformity in the measurement of the psychological impact of thrombophilia testing.

[A multicentre randomised clinical trial to evaluate the benefit of testing for thrombophilia following a first venous thromboembolism: the NOSTRADAMUS study]. / Een multicentrisch gerandomiseerd klinisch onderzoek naar het nut van trombofilietests bij een eerste veneuze trombo-embolie: het NOSTRADAMUS-onderzoek.

It is unknown whether testing patients for thrombophilia after a first episode of venous thromboembolism (VTE) and prolonging anticoagulant treatment in those with thrombophilia is justified. The NOSTRADAMUS trial, a multicentre randomised controlled trial, is being conducted to assess whether this strategy is beneficial in terms of clinical outcomes, quality of life and costs. Patients with a first VTE will be randomly assigned to one of two groups. The first group will be tested for thrombophilia and subsequently receive the test results; those in the second group will be tested but the results will not be disclosed. A total of 1336 patients will be included. Additional anticoagulant treatment for a predefined period will be initiated in patients found to have thrombophilia, while others will receive a standard predefined duration oftreatment. Primary outcomes are the risk of recurrent VTE, clinically important bleeding and the composite outcome of both. Other outcomes include overall quality of life and costs associated with outcome measures 18 months after the initial episode of VTE.

Lack of proactive inhibition in a psychomotor task at two retention intervals.

One form of the Tsai-Partington numbers test was given for 0, 1, 8, or 19 original learning trials, and a different form was given for 10 transfer learning trials. Retention of transfer learning was tested after 24 hr for half of the subjects and after 2 min and again after 24 hr for the remainder of the subjects. Amount of forgetting of transfer learning increased with the length of the retention interval, but was not affected by the number of original learning trials; i.e., no proactive inhibition was observed. Also, performance during the transfer phase of the experiment was not significantly related to the number of original learning trials; no transfer was demonstrated. A previous study had found substantial retroactive inhibition with this task.