Venous thromboembolism in medical patients treated in the setting of primary care: A nationwide case-control study in Italy

Objectives

The risk of venous thrombotic events (VTE) among medical outpatients is still not clear and it remains to be clarified whether medical diseases involve the same risk if managed at home or in hospital. The aim of this study was to evaluate in the setting of outpatient family medicine the relationship between VTE and medical conditions known to be at risk during a hospital stay.

Design and setting

The study involved a nationwide retrospective observation according to a nested case-control method; 400 general practitioners throughout Italy constituted the network for data collection. Between 2001 and 2004, all cases recorded as having VTE were entered; ten control patients without VTE, matched by sex, physician, and age, were selected from the database for each case.

Results

The eligible population comprised 372,000 patients and 1,624 incident VTE were recorded. Univariate analysis indicated hospitalization (OR 5.02; 95% CI 4.01-6.29), cancer (OR 3.06; 95% CI 2.47-3.79), acute infectious disease (OR 2.93; 95% CI 1.94-4.43), neurological disease (OR 2.60; 95% CI 1.56-4.33), congestive heart failure (CHF) (OR 2.48; 95% CI 1.68-3.69), paralysis (OR 1.87; 95% CI 1.51-2.32), COPD (OR 1.58; 95% CI 1.29-1.95), stroke (OR 1.62; 95% CI 1.24-2.12), superficial venous thrombosis (OR 1.51; 95% CI 1.11-2.04, and rheumatic diseases (OR 1.49; 95% CI 1.28-1.74) as significantly associated with an increased risk for VTE. After adjustment, only transient or definitive paralysis, cancer, acute infectious disease, congestive heart failure, neurological diseases, and previous hospitalization remained associated.

Conclusions

This large study indicates that VTE outpatients seen by general practitioners in Italy have a high prevalence of the same medical diseases associated with VTE among patients treated in hospital.     

Temperament and character as predictors of fatigue-induced symptoms among school children in Japan: a 1-year follow-up study

Objective

This 1-year follow-up study was performed to examine the association of temperament and character dimensions with new onset of fatigue-induced symptoms among school children in Japan, focusing on the transition from childhood to early adolescence.

Method

This study prospectively reviewed data from 1512 school children from four elementary and four junior high schools in Japan. The survey was conducted in 2006 and 2007. Multivariate logistic regression analyses were performed to examine the association of psychological dimensions, assessed by the Junior Temperament and Character Inventory, with fatigue-induced symptoms.

Results

The correlation between temperament and character dimensions with new-onset of fatigue-induced symptoms differed as the students advanced into higher grades. In terms of physical symptoms in males, traits correlated with fatigue-induced symptoms included Novelty Seeking (headaches OR, 1.36; 95% CI, 1.07-1.73) or Reward Dependence (extreme tiredness OR, 1.84; 95% CI, 1.09-3.12; muscle weakness OR, 2.32; 95% CI, 1.28-4.20) during elementary school, whereas in females, Novelty Seeking was mainly associated with both physical (morning fatigue OR, 1.40; 95% CI, 1.10-1.77; headaches OR, 1.22; 95% CI, 1.04-1.43) and mental (mood changes OR, 1.30; 95% CI, 1.09-1.56) symptoms. Among ninth graders, more mental symptoms of fatigue were associated with Harm Avoidance (males, poor motivation OR, 1.20; 95% CI, 1.02-1.42; females, mood changes OR, 1.25; 95% CI, 1.06-1.49) and Self Directedness (males, poor motivation OR, 0.75; 95% CI, 0.59-0.96; females, difficulty thinking OR, 0.78; 95% CI, 0.62-0.98).

Conclusion

Confirmation that the correlation between personality traits and fatigue-induced symptoms changes with grade at school has implications for screening susceptible children and adolescents and may help prevent the occurrence of such symptoms at an early stage.     

Effectiveness and safety of thromboprophylaxis with enoxaparin in medical inpatients

Background

Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism. Although effective prophylaxis exists for medical patients, there is little information outside of clinical trials. We will analyze our experience in the prophylaxis of VTE with enoxaparin in hospitalized medical patients.

Material and methods

We studied all of the patients ≥ 15 years admitted for emergency care to all of the medical departments of the hospital, except for the Hematology Department, between 1/April/1999 and 31/December/2005. The patients’ age, sex, Charlson comorbidity index (CCI), whether they received prophylaxis with enoxaparin or not, dose, VTE, bleeding, thrombocytopenia, and mortality were analyzed.

Results

40,349 patients were included, of which 55.87% were male, with an average age of 67.56, and an average CCI of 4.99. There were 19,834 patients who did not receive prophylaxis for which the rate of incidence of VTE was 0.61%, mortality 8.75%, bleeding 1.38%, and thrombocytopenia 0.04%. Prophylactic enoxaparin was administered to 20,515 patients, for which the rate of incidence of VTE was 0.44%, mortality 10.71%, bleeding 1.1%, and thrombocytopenia 0.04%. The adjusted Odds Ratio (OR) for VTE was 0.65 (95% confidence interval [95% CI] 0.49 to 0.87). The adjusted OR for mortality was 0.84 (95% CI 0.78 to 0.9). With the adjusted data, the number needed to treat (NNT) for VTE was 470.3 (95% CI 278.4 to 1413.3), and the NNT for mortality was 77.2 (95% CI 54.6 to 130.3).

Conclusion

Thromboprophylaxis with enoxaparin in hospitalized medical patients is associated with a lower incidence of VTE and mortality, and is safe.     

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 64 years 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.     

Sex-specific risk factors for recurrent venous thromboembolism

Background

Men have higher risk of recurrent venous thromboembolism (VTE) than women but this sex difference remains unexplained. In addition, whether men and women share same risk factors for recurrent VTE is unclear.

Methods

In a prospective cohort study, 583 patients (234 men and 349 women) aged 18 to 90, with a first idiopathic VTE, were followed for an average of 28 months. We assessed the association between baseline characteristics and VTE recurrence by gender.

Results

Recurrent VTE occurred in 38 women and 36 men (incidence = 4.6% and 7.5% per year respectively; HR = 1.6; 95% CI, 1.0-2.6). This relation between sex and recurrent VTE was more pronounced in patients younger than 50 years and in the presence of factor V Leiden (FVL) mutation. Multivariate analyses showed that obesity (HR, 2.8 (95% CI, 1.3-6.0)) and aging (HR, 1.3 (95% CI, 1.1-1.4) per 10 years increase) were related to an increased risk of recurrent VTE in women while FVL mutation (HR, 3.5 (95% CI, 1.5-8.1)) was a risk factor of recurrent VTE among men.

Conclusion

Men and women do not share the same risk factors for recurrent VTE. Consequently, gender has to be taken into account to improve the risk stratification and prevention of VTE recurrence.     

Association of elevated soluble P-selectin levels with fetal loss in women with a history of venous thromboembolism

Introduction

An association between pregnancy complications such as fetal loss with inherited and acquired thrombophilic defects has frequently been reported. Recently, the cell adhesion molecule P-selectin has been identified to be a strong risk factor for venous thromboembolism (VTE).

Patients and Methods

The aim of our study was to investigate whether soluble P-selectin (sP-selectin) is also associated with fetal loss (e.g. miscarriage or stillbirth) in 304 women (median age [25th-75th percentile]: 45 [37-54] years) with a history of VTE, in whom data on pregnancy-associated complications had been evaluated. At the time of sP-selectin measurement none of the women was pregnant or had an acute VTE.

Results

The prevalence of miscarriage was 21.4% and that of stillbirth was 4.6%. The median sP-selectin level of the total study population was 38.0 [31.7-44.4] ng/mL. In subjects with elevated sP-selectin levels (defined as sP-selectin ≥ 44.4 ng/mL, representing the 75th percentile of levels in the study population) the prevalence of stillbirth was significantly higher compared to those with lower levels (10.5% vs. 2.6%, p = 0.008), whereas no statistically significant difference in the prevalence of miscarriage was observed between women with and without elevated sP-selectin (17.1% vs. 22.9%, p = 0.303). The odds ratio [95% CI] of elevated sP-selectin was 4.2 [1.5-12.7] for stillbirth and 0.7 [0.4-1.3] for miscarriage.

Conclusions

Elevated sP-selectin plasma levels were associated with a 4.2-fold risk for stillbirth in women with a history of VTE. Our data support a possible role of P-selectin in late pregnancy loss.     

Attitudes towards and practice of venous thromboembolism prevention in general internal medicine wards: a multinational survey from member countries of the European Federation of Internal Medicine

Introduction

Hospitalised patients in Internal Medicine departments are at risk of venous thromboembolism (VTE). Adherence to risk stratification methods is poor. We conducted a survey among Internists from member countries of the European Federation of Internal Medicine (EFIM) to assess current knowledge and attitude towards VTE prevention.

Methods

A multinational survey of Internists affiliated to EFIM.

Results

226 physicians from 30 countries were included. Seventy nine percent of the physicians were aware of clinical guidelines to prevent VTE. Most considered their knowledge of the guidelines to be moderate. Many had not updated their knowledge recently. The magnitude of the clinical problem was over- and underestimated by many (12.2% and 40.1%, respectively). Only 46.7% thought their patients were mostly receiving proper prophylaxis. Sixty four percent worked in departments without a formal VTE prophylaxis program. Risk of bleeding, lack of awareness and lack of decision support systems were the three most common reasons for deferring treatment (88.6%, 32.3% and 27.9%, respectively). Most of the participants stated that they strongly believe in VTE prophylaxis as an intervention that prevents morbidity and mortality.

Conclusions

Despite general awareness of clinical guidelines, many medical wards do not have formal risk assessment methodologies incorporated into their operative workflow. This gap, as well as fear of complications, may be one of the reasons for the low rates of adherence reported by physicians. We speculate that perhaps current guidelines have not been accepted by Internists due to paucity of well defined and validated risk assessment tools.     

Clinical predictors of recurrent venous thromboembolism: a single institute experience in Korea

Introduction

Racial disparities in incidence rate as well as risk factors for venous thromboembolism (VTE) exist between Asian and Western populations. Moreover, predictors for recurrent VTE were not identified in Asians. Thus, this study was undertaken to investigate risk factors for recurrent VTE events in Korean people.

Materials and Methods

Three hundred-three patients newly diagnosed as VTE were enrolled from Seoul National University Hospital. Recurrence rate based on risk factors for VTE were investigated. Cumulative incidence of recurrent VTE was calculated by the Kaplan and Meier method. Independent predictors for VTE were determined using Cox proportional hazards model.

Results

After a median follow-up of 44 months, 24 (8%) of 303 patients relapsed for a total observation time of 1,217 patient-year. Cumulative incidences of recurrent VTE were 3% at 1 year, 10% at 5 years, and 18% at 8 years. Independent predictors for recurrent VTE were presence of residual thrombosis (hazard ratio [HR] = 3.1, 95% confidence interval [CI] 1.0-9.3; p = 0.044), antiphospholipid syndrome (APS) (HR = 4.3, 95% CI 1.0-19.0; p = 0.052), and age 50 years or younger (HR = 2.5, 95% CI 1.0-6.6; p = 0.053) by multivariate analysis. Residual thrombosis and APS remained predictive of recurrence by the anticoagulation-period stratified analysis.

Conclusions

In contrast to Western populations, Korean patients with VTE had the lower recurrent rate. Extended anticoagulation is necessary for Korean patients with residual thrombosis or APS.     

Prevalence of arterial and venous thromboembolic events in diabetic patients with and without the metabolic syndrome: a cross sectional study

Background

Metabolic syndrome (MS) is associated with an increased risk of cardiovascular events. Recent studies have found a higher prevalence of the MS in patients with idiopathic venous thromboembolic events (VTE) compared to controls suggesting a role of the MS in the pathogenesis of VTE.The presence of MS was shown to further increase the risk of arterial cardiovascular diseases (CVD) in diabetic patients. Conversely, there are no studies that have compared the risk of VTE in diabetic patients with and without the MS.

Methods

A cross sectional study comparing the prevalence of arterial cardiovascular events and VTE in diabetic patients with and without the MS was conducted.

Results

Nine hundred and fifty three patients were included in the study; 85.7% of patients had MS.Patients with the MS had an increased prevalence of CVD as compared with those without (23.4% vs. 11.8%) and the MS was an independent predictor of CVD in diabetic patients (OR 3.16, 95%CI 1.78, 5.59) after multiple logistic regression analysis. The prevalence of VTE was higher in patients with the MS in comparison to patients without the MS, but this association was not statistically significant (3,43% vs 1.47%; OR 2.38, 95% CI 0.56, 10.10%).

Conclusion

Our study confirms the role of MS as an adjunctive cardiovascular risk factor in patients with diabetes. There is insufficient evidence to evaluate the role of the as an adjunctive risk factor for VTE in these patients. Further studies are necessary to confirm or refute these preliminary findings.     

Darexaban (YM150) prevents venous thromboembolism in Japanese patients undergoing major abdominal surgery: Phase III randomized, mechanical prophylaxis-controlled, open-label study

Introduction

Darexaban (YM150) is an oral direct factor Xa inhibitor in clinical development for prophylaxis of venous thromboembolism (VTE) after major orthopaedic surgery. The objective of this study was to assess the efficacy and safety of darexaban 15 mg twice daily (bid) in Japanese patients undergoing major abdominal surgery.

Materials and Methods

In a Phase III, multicentre, randomized, open-label, mechanical prophylaxis-controlled, parallel-group study, adult patients (aged ≥ 40 years) were randomized to darexaban 15 mg bid or mechanical prophylaxis, for 28 days. The primary efficacy outcome was incidence of total VTE at Day 12. Adverse events (AEs) and bleeding events were recorded throughout the study.

Results

The total VTE incidence at Day 12 was 2.6% in the darexaban 15 mg bid group (95% confidence interval [CI]: 0.32, 9.07), compared with 15.0% (95% CI: 5.71, 29.84) in the mechanical prophylaxis group. During the investigational period, the incidence of all bleeding events was 9.5% in the darexaban 15 mg bid group and 3.9% in the mechanical prophylaxis group. In the darexaban 15 mg bid group, one patient experienced major bleeding and five patients experienced clinically relevant non-major (CRNM) bleeding. No patients in the mechanical prophylaxis group experienced major and/or CRNM bleeding. AEs were reported in 71.4% of patients in the darexaban 15 mg bid group and 76.5% of patients in the mechanical prophylaxis group; the most frequent AEs across both treatment groups were constipation and insomnia. No patients died during the study.

Conclusions

Based on these findings, darexaban is expected to be effective for the prevention of VTE in patients undergoing major abdominal surgery.(Clinical trial registration number: NCT00942435)     

Psychosocial and coping responses within the community health care setting towards a national outbreak of an infectious disease

Objective

The psychological and coping responses of the noninfected community towards infectious disease outbreaks are relatively understudied. This cross-sectional study sought to determine the prevalence of severe acute respiratory syndrome (SARS)-related psychiatric and posttraumatic morbidities and associated coping styles within the general population visiting community health care services.

Methods

It was conducted on individuals attending community polyclinics in Singapore within the first week of July 2003, 16 weeks after the first national outbreak of SARS. The General Health Questionnaire-28, Impact of Event Scale-Revised, and Brief COPE were used to determine the prevalence rates of psychiatric and posttraumatic morbidities and employed coping strategies respectively.

Results

The overall response rate was 78.0%. Of the 415 community health care setting respondents, we found significant rates of SARS-related psychiatric (22.9%) and posttraumatic morbidities (25.8%). The presence of psychiatric morbidity was associated with the presence of high level of posttraumatic symptoms [adjusted odds ratio (OR) 2.26, 95% confidence interval (CI) 1.24-4.13, P=.008]. Psychiatric morbidity was further associated with being seen at fever stations (adjusted OR 1.90, 95% CI 1.08-3.34, P=.026), younger age (adjusted OR 0.97, 95% CI 0.94-0.98, P=.021), increased self blame (adjusted OR 1.67, 95% CI 1.22-2.28, P=.001), less substance use (adjusted OR 0.74, 95% CI 0.56-0.98, P=.034) and posttraumatic morbidity was associated with increased use of denial (adjusted OR 1.31, 95% CI 1.04-1.67, P=.024), and planning (adjusted OR 1.51, 95% CI 1.16-1.95, P=.002) as coping measures.

Conclusion

These findings could potentially inform the development of practical community mental health programs for future infectious disease outbreaks.     

The G534E-polymorphism of the gene encoding the Factor VII-activating protease is a risk factor for venous thrombosis and recurrent events

Introduction

A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinical role has so far been controversial in part due to small cohort sizes. The aim of the present case-control study was to elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the development of venous thromboembolic disease (VTE) with other known sequence variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963).

Materials and Methods

The study included 891 patients (312 male and 579 female) with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 1283 healthy blood donors with no history of venous thromboembolic disease.

Results

We found that besides to the well-established aforementioned sequence variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95% CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95% CI)). Comparing patients displaying one or more events FSAP-MI was still associated with the development of recurrent thromboembolic events (1.64 (1- 2.69) OR (95% CI)).

Conclusions

We conclude that FSAP Marburg-I genotyping may be used to determine the risk for thromboembolic disorders in patients with suspected thrombophilia and known DVT or PE.     

Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: A systematic review

Introduction

Many studies evaluated the association of V617F Jak-2 with the risk of thrombosis in patients with essential thrombocythaemia, but the results of these studies were inconsistent. Few studies evaluated the association of V617F Jak-2 mutation with the risk of thrombosis in patients with idiopathic myelofibrosis. Therefore, we performed a systematic review of the studies that assessed the risk of thrombosis associated with V617F Jak-2 in patients with ET or IM.

Materials and Methods

We searched MEDLINE and EMBASE databases and reference lists of retrieved articles. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated for each trial and pooled.

Results

We included 21 studies involving patients with essential thrombocythaemia and 6 studies patients with idiopathic myelofibrosis. In essential thrombocythaemia patients, V617F Jak-2 was associated with a significant increased risk of thrombosis (OR 1.92, 95% CI 1.45-2.53), both of venous (OR 2.49, 95% CI 1.71-3.61) and arterial (OR 1.77, 95% CI 1.29-2.43) vessels. In idiopathic myelofibrosis patients, the risk of thrombosis associated with V617F Jak-2 tended to be increased (OR 1.76, 95% CI 0.91-3.41).

Conclusions

Our systematic review suggests that V617F Jak-2 increases the risk of thrombosis in essential thrombocythaemia patients by about two fold while its role in idiopathic myelofibrosis patients is uncertain.     

Changes in mental health as a predictor of changes in working time arrangements and occupational mobility: Results from a prospective cohort study

Objective

The aim of this prospective study was to gain insight into a possible causal relationship between mental health and characteristics of the work situation.

Methods

Using longitudinal data from the Maastricht Cohort Study, this study examines whether deterioration in mental health (prolonged fatigue, need for recovery, and psychological distress) results in a subsequent change in working time arrangements (assessed by means of logistic regression analysis) or occupational mobility (assessed by means of Cox regression analysis).

Results

Compared to employees not experiencing a deterioration in mental health, employees who became a prolonged fatigue case were more likely to reduce their working hours (OR 2.49; 95% CI 1.42-4.35) and leave a shift work job (OR 3.44; 95% CI 1.42-8.38). Employees who became a need for recovery case were more likely to reduce their working hours (OR 2.83; 95% CI 1.53-5.26) or change jobs within the company (RR 1.31; 95% CI 1.07-1.61). Employees who became a psychological distress case were more likely to change jobs within the company (RR 1.38; 95% CI 1.16-1.65) or to change jobs from one employer to another (RR 1.45; 95% CI 1.03-2.03).

Conclusion

The results of this study provide evidence for a possible causal relationship between deterioration in mental health and subsequent change in working time arrangements or occupational mobility. These results suggest that workers adapt to the onset of a mental health problem by reducing their working hours, by leaving a shift work job, by changing jobs within the company, or by changing jobs from one employer to another.     

The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis

Background

The association between antiphospholipid antibodies (APLA) and placenta mediated pregnancy complications (pre-eclampsia, intrauterine growth restriction (IUGR), late fetal loss and placental abruption) remains controversial.

Methods

We performed a systematic review of published case-control, cohort and cross sectional studies (MEDLINE (1975 to 2009), EMBASE 16 (1980 to 2009) and all EBM Reviews (2009)) to evaluate the association between APLA and placenta mediated complications in untreated women without autoimmune diseases.

Results

Our search strategy identified 1207 potentially relevant studies. Twenty eight were included in the final analysis. LA was associated with pre-eclampsia (OR 2.34; 95%CI 1.18-4.64), IUGR (OR 4.65 95% CI 1.29-16.71) and late fetal loss (OR 4.73; 95%CI 1.08-20.81) amongst case-control studies and only with late fetal loss (OR 10.59 95% CI 1.87-59.88) amongst cohort studies. ACA were associated with pre-eclampsia (OR 1.52; 95%CI 1.05-2.20) and late fetal loss (OR 4.29; 95% CI 1.34-13.68) amongst case-control studies and only late fetal loss (OR 8.85 95% CI 1.84-42.50) amongst cohort studies. Finally, anti-B2 GP1 antibodies showed associations with pre-eclampsia (OR 19.14, 95% CI 6.34-57.77), IUGR (OR 20.03; 95%CI 4.59-87.43) and late fetal loss (OR 23.46, 95% CI 1.21-455.01) in two cohort studies.

Conclusion

APLAs appear to be associated with late fetal losses. However, the association between APLAs and other placenta mediated complications is inconsistent. LA is most strongly and consistently associated with placenta mediated complications. There are currently insufficient data to support a significant link between anti-B2 GP1 antibodies and pregnancy morbidity.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.     

Systemic and local factors associated with coronary plaque disruption

Introduction

Yellow plaques are regarded vulnerable; and disrupted yellow plaques are the major cause of acute coronary syndrome. We examined the factors associated with the disruption of yellow plaques among patients and lesion characteristics.

Materials and Methods

Consecutive 161 patients with ischemic heart diseases who received coronary angioscopic examination were analyzed. Yellow plaques in the segments to which intervention had never been performed were included, and their yellow color grade and presence/ absence of disruption were examined. Associated factors for plaque disruption were examined among patients and lesion characteristics.

Results

In 161 patients, 392 yellow plaques were included for analysis and 70 of them were disrupted. Frequency of plaque disruption (= disrupted / all yellow plaques) was significantly higher at the segments of severer stenosis (stenosis≥75% vs. 75-25% vs. < 25%: 34% vs. 21% vs. 14%, p = 0.006). Multivariate analysis revealed angiographic stenosis (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.005-1.023; p = 0.003), yellow color grade (OR, 3.297; 95% CI, 2.062-5.273, p < 0.001), LDL-cholesterol (OR, 1.012; 95% CI, 1.004-1.020, p = 0.003), male gender (OR, 3.608; 95% CI, 1.538-8.465; p = 0.003), and hypertension (OR, 2.552; 95% CI, 1.094-5.953; p = 0.030) as significant associated factors for plaque disruption.

Conclusion

Angiographic stenosis, yellow color grade, LDL-cholesterol, male gender, and hypertension were significantly associated with the disruption of yellow plaques.     

Statin use in patients with nephrotic syndrome is associated with a lower risk of venous thromboembolism

Background

Nephrotic syndrome (NS) is a well-known risk factor for venous thromboembolism (VTE), however preventive measures are not routinely taken. In non-renal populations, statins are associated with lower risk of VTE. Hence, we set up this single-center retrospective cohort study to assess whether statin use influenced VTE risk in NS subjects.

Methods

We analyzed 289 consecutive patients with NS (defined by proteinuria ≥ 3.5 g/day) who were aged > 18 years at the study entry and followed for at least 6 months. Use of statins and concomitant medication were determined.

Results

Of patients with NS (59% men; mean age, 42 years), 48% used statins for at least 1 month during NS. Using univariate and time-dependent Cox regression analyses, hazard ratio for VTE in statin users versus non-users was 0.2 (95%CI, 0.1-0.7) and 0.6 (95% CI, 0.2 -2.0), respectively. Adjustments for potential confounders did not change outcomes. Three VTE events occurred in a total of 812 statin-years, corresponding to an annual incidence of 0.37% (95%CI, 0.12-1.15). In contrast, 17 VTE occurred in a total of 2106 patient-years without statin exposure, annual incidence 0.81% (95%CI, 0.50-1.30).

Conclusions

Although statistically significant, the hazard ratio of 0.2 for VTE risk in statin users versus non-users could have been biased, but the time-dependent hazard ratio of 0.6 was probably not. As the association was in the same direction for both analyses, we conclude that statin use is associated with a lower risk of VTE in patients with NS.     

Efficacy and safety of enoxaparin in Japanese patients undergoing curative abdominal or pelvic cancer surgery: Results from a multicenter, randomized, open-label study

Background

Enoxaparin sodium (enoxaparin) is used worldwide for the prevention of venous thromboembolism (VTE). Registration trials of enoxaparin have been conducted primarily in Caucasian populations, and its preventive use in Japanese patients has yet to be established. To address this, we evaluated the efficacy and safety of postoperative enoxaparin in Japanese patients undergoing surgery for abdominal cancer.

Methods

This multicenter, open-label study randomized 151 Japanese patients undergoing curative surgery for abdominal cancer to enoxaparin 20 mg twice daily for 14 days, started 24-36 hours after surgery (n = 113) or intermittent pneumatic compression (IPC) as a reference (n = 38). IPC was performed at least once in both groups between randomization and surgery. The primary efficacy endpoint was the incidence of VTE in the modified intention-to-treat (mITT) population. The primary safety outcome was the incidence of any bleeding during treatment and follow-up.

Results

Incidence of VTE was 1.2% (95% CI, 0.03-6.53%) (1/83 patients) in the enoxaparin group and 19.4% (95% CI, 7.45-37.47%) (6/31 patients) in the IPC group. In the safety population, 10/109 patients in the enoxaparin group (9.2%; 95% CI, 4.49-16.23%) and 3/38 patients in the IPC group (7.9%; 95% CI, 1.66-21.38%) experienced a bleeding event. There were no cases of fatal bleeding or bleeding into any critical organ.

Conclusions

These favorable efficacy and safety data support the use of enoxaparin (20 mg twice daily for 14 days started 24-36 hours after surgery) in Japanese patients undergoing abdominal or pelvic cancer surgery.     

Incidence and characteristics of asymptomatic distal deep vein thrombosis unexpectedly found at admission in an Internal Medicine setting

Introduction

Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department.

Materials and methods

Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12 weeks.

Results

One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p = 0.014, p = 0.009 and p = 0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p = 0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients.

Conclusions

We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.