Deficient inhibition of return in chronic but not first-episode patients with schizophrenia

Background

Inhibition of return (IOR) has been tested in patients with schizophrenia with contradictory results. Some studies indicated that patients with schizophrenia have normal levels of IOR; however, other studies reported delayed or blunted IOR. Inconsistency in findings might be due to differences across studies in relevant aspects associated with disease, such as heterogeneity of the disorder, different medications, onset and severity of the illness. The present study was to explore different patterns of IOR in antipsychotic medication free first-episode schizophrenia and chronic schizophrenia.

Methods

Forty two patients with first-episode schizophrenia, 44 patients with chronic schizophrenia, and 38 healthy controls were included in the study. All subjects went through a covert orienting of attention task with seven stimulus onset asynchrony (SOA) intervals (400 ms, 500 ms, 600 ms, 700 ms, 800 ms, 1200 ms and 1500 ms).

Results

Compared with healthy controls, the magnitude and onset of IOR in first-episode patients with schizophrenia were intact. However, in patients with chronic schizophrenia, there was an attenuated cuing effect especially at SOA 700 ms; in addition, there was a robust IOR until at SOAs 800 ms or above. Moreover, the illness duration and the number of psychotic episodes were significantly correlated with the validity effect at SOAs 400 ms and 600 ms.

Conclusion

Our study suggests that deficient IOR presents in chronic but not in first-episode patients with schizophrenia. IOR deficit in schizophrenia may begin during the course of illness and deteriorate over the course of illness. Our findings are consistent with the neurodegenerative model of schizophrenia.     

Correlates of psychiatric hospitalization in a clinical sample of Canadian adolescents with bipolar disorder

Objective

To identify factors associated with psychiatric hospitalization among adolescents with bipolar disorder (BD).

Methods

Participants were 100 adolescents, ages 13–19, who fulfilled DSM-IV criteria for bipolar I disorder [(BD-I), n = 26], bipolar II disorder [(BD-II), n = 40], or operationalized criteria for BD not otherwise specified [(BD-NOS), n = 34], via the Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version (KSADS-PL). Demographic, clinical, and family history variables were measured via clinical interview with the participant and a parent or guardian.

Results

The lifetime prevalence of psychiatric hospitalization was 50%. Significant predictors of psychiatric hospitalization in univariate analyses included older age, BD-I, history of suicide attempt, psychosis, lifetime use of second generation antipsychotics (SGAs), lithium, SSRI antidepressants and any medication. BD-II was negatively associated with psychiatric hospitalization. In multivariable analyses, older age, history of suicide attempt, psychosis and use of SGAs were positively associated with hospitalization, whereas BD-II was negatively associated with hospitalization.

Conclusions

Psychiatric hospitalization in adolescents with BD is highly prevalent and associated with older age and proxies for greater illness severity. Further studies are needed to identify strategies for reducing the need for psychiatric hospitalizations among adolescents with BD.     

Temperament and character in individuals at ultra-high risk for psychosis and with first-episode schizophrenia: Associations with psychopathology,psychosocial functioning,and aspects of psychological health

Objective

The psychobiological model of temperament and character indicates that personality traits are heritable and, during development, constantly influence one’s susceptibility to schizophrenia. Our objective was to evaluate temperament and character in subjects at ultra-high risk (UHR) for psychosis and individuals with first-episode schizophrenia.

Methods

UHR for psychosis subjects (n = 50), first-episode schizophrenia patients (n = 33), and normal controls (n = 120) were compared on temperament and character dimensions, and correlation analysis of each personality dimension with psychopathologies, global and social functioning, and self-esteem. General and social self-efficacy reports were conducted. UHR subjects were followed-up for 24 months and the baseline personality dimensions were compared between the converted and non-converted groups.

Results

Both clinical groups showed abnormal personality traits in terms of temperament (higher harm avoidance, lower reward dependence and persistence) and character (lower self-directedness and cooperativeness). Psychosocial functioning and psychological health components were found to be correlated with some personality dimensions. The conversion rate of overt psychotic disorder was 25.0% at the 24-month follow-up. Baseline cooperativeness dimension was a significant predictive dimension for conversion into overt psychosis in the UHR group during the follow-up period.

Conclusion

Patients with first episode schizophrenia have a pervasively altered personality profile from normal controls. More importantly, this altered personality profile already emerged in putative prodromal, UHR individuals. The present findings indicate that certain personality traits can play a protective or vulnerable role in developing schizophrenia.     

Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

Background

The β3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression.

Methods

The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MDD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls.

Results

No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P = 0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P = 0.027).

Conclusions

We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity.     

Factors associated with the development of superficial vein thrombosis in patients with varicose veins

Introduction

Superficial vein thrombosis (SVT) is a common and controversial clinical entity. Recent studies have demonstrated that SVT should be seen as a venous thromboembolism (VTE). The objective of this study was to investigate the prevalence of thrombophilia defects and to estimate the role of age, sex and body mass index (BMI) in patients with varicose veins (VVs) and SVT.

Materials and Methods

A total of 230 patients with VVs, 128 with, and 102 without SVT underwent thrombophilia testing included factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase and plasminogen activator inhibitor- 1 mutations, protein C, protein S (PS), anti-thrombin III and plasminogen deficiencies and levels of A₂ antiplasmin, activate protein C resistance and lupus anticoagulant. According to Clinical- Etiology- Anatomy- Pathophysiology (CEAP) classification patients were categorized in two subgroups: moderate disease (C_2,3) and severe disease (C_4,5,6). Age and body mass index were also assessed.

Results

The prevalence of thrombophilia defects was significantly higher in patients with moderate disease and SVT (p = 0.002). In the C_2,3 group, SVT was associated with PS deficiency (p = 0.018), obesity (p < 0.001), male gender (p = 0.047) and age (p < 0.001). There were no significant differences in patients with severe disease.

Conclusions

Age, male sex, obesity and PS deficiency are factors associated with SVT development among patients with VVs having moderate disease (C_2,3).     

Post-marketing surveillance of thrombomodulin alfa,a novel treatment of disseminated intravascular coagulation - Safety and efficacy in 1,032 patients with hematologic malignancy

Introduction

Post-marketing surveillance of thrombomodulin alfa (TM-α) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy.

Materials and methods

All patients treated with TM-α from May 2008 to April 2010 in Japan were included. Information about baseline characteristics, safety, and efficacy were collected. The DIC resolution rate, survival rate on Day 28 after the last TM-α administration, and changes in DIC score and coagulation tests were evaluated.

Results

The underlying diseases associated with DIC were acute myeloid leukemia (except for acute promyelocytic leukemia, n = 350), lymphoma (n = 199), acute promyelocytic leukemia (n = 172), acute lymphoblastic leukemia (n = 156), myelodysplastic syndromes (n = 61), and other (n = 94). The incidence rates of bleeding-related adverse events and adverse drug reactions were 17.8% and 4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were assessed as disappeared or improved based on symptoms after TM-α treatment. The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC score and coagulation tests including thrombin-antithrombin complex (TAT) were significantly improved. Coagulation tests were significantly improved after TM-α treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated.

Conclusions

This surveillance confirmed the safety and efficacy of TM-α in clinical practice, thus TM-α may be an ideal treatment for patients with DIC based upon hematologic malignancy.     

The predictive value of heart-type fatty acid-binding protein is independent from symptom duration in normotensive patients with pulmonary embolism

Background

Heart-type fatty acid-binding protein (H-FABP) is a useful biomarker for risk stratification of patients with pulmonary embolism (PE). In patients with acute myocardial infarction, H-FABP plasma concentrations rise after 30 minutes and return to normal within 20-24 hours. We tested whether the predictive value of H-FABP is affected by the duration of symptoms prior to diagnosis in patients with PE.

Material and Methods

We prospectively studied 257 consecutive normotensive patients with confirmed symptomatic PE.

Results

Patients with acute (< 24 hours; n = 150) symptom onset presented more often with syncope (28.7% vs. 6.5%; p < 0.001) compared to patients with symptoms ≥ 24 hours (n = 107); other baseline characteristics, comorbidities, and risk factors were distributed equally. Patients with an adverse 30-day outcome (6.6%) had higher H-FABP levels (11.84 [3.57-19.62] ng/ml) compared to patients with a favorable course (3.42 [1.92-5.42] ng/ml; p < 0.001). However, the proportion of patients with H-FABP levels ≥ 6 ng/ml did not differ among patients with acute symptom onset and late presentation (p = 0.104). Only tachycardia and elevation of H-FABP were associated with an increased risk of an adverse 30-day outcome both in patients with acute symptom onset (H-FABP: OR, 5.8; 95% CI, 1.4-24.5; p = 0.016; tachycardia: 7.0 [1.4-36.0]; p = 0.018) and late presentation (H-FABP: 9.3 [2.0-43.2]; p = 0.004 and tachycardia: 12.3 [1.5-103.6]; p = 0.021). The prognostic value could further be improved by the use of a simple H-FABP-based clinical prediction score.

Conclusions

Our findings indicate that H-FABP is a useful biomarker for risk stratification of normotensive patients with PE regardless of symptom duration prior to diagnosis.     

Central emboli rather than saddle emboli predict adverse outcomes in patients with acute pulmonary embolism

Introduction

In patients with acute pulmonary embolism (PE), the prognostic implications of saddle or central emboli, as observed on computed tomography (CT), remain to be established. The aim of the present study was to assess whether the presence of saddle and central emboli could be used to predict clinical outcomes in patients with PE.

Materials and Methods

The authors retrospectively reviewed 743 consecutive patients hospitalized at a tertiary referral center with a diagnosis of PE based on multi-detector row CT scan.

Results

All the clinical variables did not differ between saddle emboli (5.8% [n = 43]) and right or left pulmonary artery emboli (29.7% [n = 221]), and the frequency of an adverse outcome was not significantly different between the two groups. Saddle emboli and right or left pulmonary artery emboli were grouped into central emboli (35.5% [n = 264]). Patients were allocated to an adverse outcome group (10.5% [n = 78]) or a control group (89.5% [n = 665]). Multivariate analysis demonstrated that PE severity index (PESI) score (class IV-V), N-terminal-pro-B-type natriuretic peptide level (≥ 1,406 pg/mL), right ventricular dilation on CT (right ventricle/left ventricle diameter ratio ≥ 1), and central emboli significantly predicted an adverse outcome. The addition of central emboli to other established prognostic factors such as PESI enhanced the positive predictive values and positive likelihood ratios of an adverse outcome for acute PE.

Conclusions

Rather than saddle emboli, central emboli could be an independent prognostic factor of adverse outcomes in patients with acute PE and provide additional prognostic value when combined with other prognostic factors.     

Risk factors and clinical profile of thrombotic thrombocytopenic purpura in systemic lupus erythematosus patients. Is this a distinctive clinical entity in the thrombotic microangiopathy spectrum?: A case control study

Introduction

The association of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE) is rare. It is associated with high morbidity and mortality. Information about risk factors and clinical outcomes is scant.

Material and Methods

A retrospective case-control study was performed in a referral center in Mexico City between 1994 and 2013. Patients were diagnosed with TTP if they fulfilled the following criteria: microangiopathic haemolytic anaemia, thrombocytopenia, high LDH levels, normal fibrinogen and negative Coombs’ test. Patients with SLE were diagnosed with ≥ 4 ACR criteria. We included three study groups: group A included patients with SLE-associated TTP (TTP/SLE; cases n = 22, TTP events n = 24); patients with non-autoimmune TTP (NA-TTP; cases n = 19, TTP events n = 22) were included in group B and patients with SLE without TTP (n = 48) in group C.

Results

After multivariate analysis, lymphopenia < 1000/mm3 [OR 19.84, p = 0.037], high SLEDAI score three months prior to hospitalisation [OR 1.54, p = 0.028], Hg < 7 g/dL [OR 6.81, p = 0.026], low levels of indirect bilirubin [OR 0.51, p = 0.007], and less severe thrombocytopenia [OR 0.98, p = 0.009] were associated with TTP in SLE patients. Patients with TTP/SLE received increased cumulative steroid dose vs. NA-TTP (p = 0.006) and a higher number of immunosuppressive drugs (p = 0.015). Patients with TTP/SLE had higher survival than NA-TTP (p = 0.033); however, patients hospitalised for TTP/SLE had a higher risk of death than lupus patients hospitalised for other causes

Conclusions

Lymphopenia is an independent risk factor for TTP/SLE. It is likely that patients with TTP/SLE present with less evident clinical features, so the level of suspicion must be higher to avoid delay in treatment.     

Impulsivity in children and adolescents with mood disorders and unaffected offspring of bipolar parents

Objective

Increased impulsivity seems to be present across all phases of bipolar disorder (BD). Impulsivity may therefore represent an endophenotype for BD, if it is also found among normal individuals at high genetic risk for mood disorders. In this study, we assessed impulsivity across four different groups of children and adolescents: patients with BD, major depressive disorder (MDD) patients, unaffected offspring of bipolar parents (UO), and healthy controls (HC).

Subjects and Methods

52 patients with BD, 31 with MDD, 20 UO, and 45 HC completed the Barratt Impulsiveness Scale (BIS-11), an instrument designed to measure trait impulsivity.

Results

UO displayed significantly higher total BIS-11 impulsivity scores than HC (p = 0.02) but lower scores than BD patients (F = 27.12, p < 0.01). Multiple comparison analysis revealed higher BIS-11 total scores among BD patients when compared to HC (p < 0.01) and UO (p < 0.01). MDD patients had higher BIS-11 scores when compared to HC (p < 0.01). Differences between MDD patients and UO, as well as between MDD and BD patients, were not statistically significant.

Conclusion

Our findings suggest that trait impulsivity is increased among children and adolescents with mood disorders, as well as in unaffected individuals at high genetic risk for BD.     

Treatment with everolimus is associated with a procoagulant state

Introduction

Renal transplant recipients are at increased risk of venous thromboembolic events, which is in part caused by their treatment with maintenance immunosuppressive drugs. Because we observed an increased incidence of venous thromboembolic events in renal transplant recipients treated with the mTOR inhibitor (mTORi) everolimus, we aimed to identify prothrombotic mechanisms of this immunosuppressive drug.

Materials and Methods

In a single center study, nested in a multi-center randomized controlled trial, we measured parameters of coagulation, anti-coagulation and fibrinolysis in renal transplant recipients, receiving the mTORi everolimus (n = 16, mTOR group) and compared them to a similar patient group, receiving a calcineurin inhibitor and/or mycophenolate sodium (n = 20, non-mTOR group). All patients were at least 6 months following transplantation with a stable transplant function.

Results

The use of an mTORi was associated with significantly higher levels of von Willebrand factor, prothrombin fragment 1 + 2, thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 as compared to a non-mTORi based immunosuppressive regimen.

Conclusions

Treatment with an mTORi leads to increased endothelial activation, thrombin formation and impaired fibrinolysis in renal transplant recipients. This suggests an increased risk of thrombotic events in renal transplant recipients treated with mTOR inhibitors. A prospective study to establish the precise risk of thrombotic events in these patients is urgently needed.     

Perceived weight in youths and risk of overweight or obesity six years later

Objective

To examine the association between perceived overweight in adolescents and the development of overweight or obesity later in life.

Methods

This paper uses data from a prospective, two-wave cohort study. Participants are 2445 adolescents 11–17 years of age who reported perceived weight at baseline and also had height and weight measured at baseline and at follow-up six years later sampled from managed care groups in a large metropolitan area.

Results

Youths who perceived themselves as overweight at baseline were approximately 2.5 times as likely to be overweight or obese six years later compared to youths who perceived themselves as average weight (OR = 2.45, 95% CI = 1.77–3.39), after adjusting for weight status at baseline, demographic characteristics, major depression, physical activity and dieting behaviors. Those who perceived themselves as skinny were less likely to be overweight or obese later (OR = 0.36, 95% CI = 0.27–0.49).

Conclusions

Perceived overweight was associated with overweight or obesity later in life. This relationship was not fully explained by extreme weight control behaviors or major depression. Further research is needed to explore the mechanism involved.     

Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single therapeutic doses in adult and elderly healthy volunteers and in subjects with varying degrees of renal impairment

Introduction

Aging and renal impairment may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis.

Materials and Methods

Open, parallel study. Healthy adult [n = 13] and elderly (> 65 yrs) [n = 12] volunteers; and subjects with mild (Cl_Cr ≥ 50 to ≤ 80 mL/min, n = 8), moderate (Cl_Cr ≥ 30 to < 50 mL/min, n = 7), and severe (Cl_Cr < 30 mL/min, n = 8) renal impairment received four prophylactic doses (3,500 IU/24 h) and a single therapeutic dose (115 IU/kg) of bemiparin with an interim washout period. Anti-FXa activity and the potential need for dose adjustment were evaluated.

Results

There were statistically significant differences in the severe renal impairment group vs. adult volunteers in all anti-FXa related parameters, but no significant differences in any of the anti-FXa related parameters between the adult and the elderly. Anti-FXa simulations after 10 prophylactic doses predicted mean A_max = 0.59 IU/mL in subjects with severe renal impairment and 0.33-0.39 IU/mL in the rest. Simulations in the severe renal impairment group with dose adjustment (2,500 IU/24 h) predicted all individual A_max < 0.60 IU/mL (mean A_max = 0.42 IU/ml). Simulations after 10 therapeutic doses predicted mean A_max = 1.22 IU/mL in severe renal impairment group and 0.89-0.98 IU/mL in the rest. Simulations in the severe renal impairment group with 75% dose adjustment predicted individual A_max ≤ 1.60 IU/mL (mean A_max = 0.91 IU/mL).

Conclusions

No dose adjustments are required in elderly with preserved renal function. A dose adjustment of bemiparin is only advisable in patients with severe renal impairment when using prophylactic or therapeutic doses.     

Circulating microparticle tissue factor,thromboembolism and survival in pancreaticobiliary cancers

Background

Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.

Patients and Methods

Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.

Results

The study population comprised 117 patients, including pancreatic (n = 80), biliary (n = 34) or unknown primary histologically consistent with PBC (n = 3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n = 15), deep venous thrombosis (n = 21) and other arterial or venous events (n = 32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity < 2.5 pg/mL (p < 0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).

Conclusions

Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.     

Symptom structure and severity: A comparison of responses to the positive and negative syndrome scale (PANSS) between patients with PTSD or schizophrenia

Objectives

To describe and compare the structure and relative severity of symptoms in clinical trial patients diagnosed with Post Traumatic Stress Disorder (PTSD) or schizophrenia using the Positive and Negative Syndrome Scale (PANSS), developed originally to evaluate symptoms of schizophrenia.

Method

This secondary data analysis used baseline PANSS symptom ratings (n = 267) from a six-month multicenter randomized placebo-controlled trial of adjunctive risperidone in patients with chronic military-related PTSD. First, using a split-half design, Exploratory Factor Analysis (EFA) was employed to identify independent factors which were then compared to published factor structures for schizophrenia. Next, Confirmatory Factor Analysis (CFA) was applied to the second half of the sample to compare the results of the EFA and published factor structures. Finally, T-tests were used to compare the severity of factor scores between the PTSD sample and the baseline PANSS ratings from the Clinical Antipsychotic Trial for Intervention Effectiveness (CATIE) schizophrenia sample (n = 1460).

Results

EFA suggested five factors similar to those identified in a summary of 29 schizophrenia studies by Wallwork (Schizophrenia Research, 137:246–250). CFA showed that the five factor Wallwork model fit the data better than the EFA, although both had relatively high goodness of fit. T-tests showed that the PTSD sample had more severe symptoms on the Depressive factor, and the schizophrenia sample on the Positive, Negative, and Disorganized factors, with no significant difference on the Excited factor.

Conclusion

Veterans with PTSD had similar symptom structure to patients with schizophrenia on the PANSS, but were less symptomatic on psychosis-related factors and more symptomatic on depression. Dimensional symptom factors can be virtually the same across diagnoses.     

The loudness dependence of the auditory evoked potential (LDAEP) in schizophrenia,bipolar disorder,major depressive disorder,anxiety disorder,and healthy controls

Background

Serotonergic dysfunction in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, and healthy controls was evaluated by measuring the activity of the loudness dependence of the auditory evoked potential (LDAEP).

Methods

The 357 subjects who were evaluated comprised 55 normal controls, 123 patients with major depressive disorder, 37 with bipolar disorder, 46 with schizophrenia, 37 with panic disorder (PD), 31 with generalized anxiety disorder (GAD), and 28 with post-traumatic stress disorder (PTSD).

Results

LDAEP was significantly stronger in healthy controls than in patients with either bipolar disorder (p = 0.025) or schizophrenia (p = 0.008), and significantly stronger in patients with major depressive disorder than in those with bipolar disorder (p = 0.01) or schizophrenia (p = 0.03). LDAEP did not differ significantly between patients with major depressive disorder and healthy control subjects (p = 0.667), or between healthy control subjects and patients with anxiety disorder, including PD (p = 0.469), GAD (p = 0.664), and PTSD (p = 0.167).

Conclusion

The findings of the present study reveal that patients with major psychiatric disorders exhibit different strengths of LDAEP according to their serotonin-related pathology. Studies controlled for psychotropic medication, menstruation cycle, and smoking are needed.     

Relationship between inflammation and metabolic syndrome following treatment with paliperidone for schizophrenia

Objective

Metabolic syndrome and antipsychotic medications are associated with inflammation. This study investigated the relationship between inflammation and metabolic syndrome in patients with schizophrenia. It also examined the effects of paliperidone extended release (ER) treatment on metabolic parameters.

Methods

Data were analyzed from schizophrenic patients who participated in a multi-center, open-label, non-comparative clinical trial. Anthropomorphic measurements (i.e., weight, waist circumference, and blood pressure) were assessed along with fasting laboratory values, including white blood cell (WBC) count, glucose, high-density lipoprotein, and triglycerides.

Results

Among the 225 patients at baseline, the group with the highest WBC count displayed a 5.9-fold risk for metabolic syndrome compared with that of the lowest group. An increase of 10³ WBCs/μL was associated with a 1.4-fold increased risk for metabolic syndrome. After 24 weeks of treatment with paliperidone ER, significant increases were observed in waist circumference and body weight. Changes in WBC count were positively correlated with changes in waist circumference.

Conclusions

Schizophrenic patients with high levels of inflammation should be carefully monitored for metabolic syndrome. Moreover, strategies to reduce inflammation and obesity may prevent metabolic syndrome in patients with schizophrenia who take atypical antipsychotic medication.     

Studies of fibrin formation and fibrinolytic function in patients with the antiphospholipid syndrome

Objective

The antiphospholipid syndrome (APS) is defined by persistent antiphospholipid antibodies together with thrombosis and/or pregnancy morbidity. We investigated the tightness of fibrin clot and fibrinolytic function in plasma samples from APS patients compared with two control groups.

Material and Methods

APS patients (n = 49), healthy controls (HC) (n = 19) and warfarin-treated nonAPS thrombosis controls (nonAPS-TC) (n = 39) were investigated. Fibrin permeability was assessed as the permeability coefficient (Ks) by a flow measurement technique. Additionally, clot density and fibrinolytic function was analysed by a turbidimetric clotting and lysis assay. Fibrin structure was visualised using scanning electron microscopy. Finally, the number of cell-derived microparticles (MPs) in the samples were correlated to fibrin permeability

Results and Conclusions

The Ks value was lower in samples from APS-patients compared to HC and nonAPS-TC (p < 0.0001 for both) indicating a less permeable fibrin clot in APS patients. Scanning electron microscopy images confirmed compact fibrin with smaller intrinsic pores and thinner fibers in samples from APS patients as compared to HC. Prolonged fibrinolysis (clot lysis) times were present in the subgroup of APS patients with previous arterial thrombosis (n = 15) as compared to HC and to nonAPS-TC (all p-values < 0.05). In conclusion, tighter fibrin clots were formed in plasma from APS patients compared with healthy controls and warfarin treated patients with thrombosis of “nonAPS origin”. This new observation presents a possible mechanism contributing to the thrombotic predisposition of APS patients. Impaired fibrinolysis, selectively present among APS patients with previous arterial thrombosis, may further aggravate the pro-thrombotic state in this APS subgroup.     

Inhibitory effects of bortezomib on platelet aggregation in patients with multiple myeloma

Introduction

Multiple myeloma (MM) therapy affects prothrombotic and anticoagulant processes. Patients receiving thalidomide, especially in combination with steroids, are at increased risk of venous thromboembolism (VTE), while the incidence of VTE on bortezomib is low. In vitro studies indicate that bortezomib causes a reduction in ADP-induced platelet aggregation.

Objectives

To analyse the influence of bortezomib on platelet aggregation induced by various agonists in patients with MM.

Patients and Methods

A total of 30 patients (median age 57.5 years) with relapsed/refractory MM receiving bortezomib-based regimens were analysed. Optical platelet aggregometry was performed with the agonists collagen, ADP and ristocetin and measured over two 21-day cycles. The results from two groups: those treated with bortezomib and thalidomide (BT group, n = 11) and those without thalidomide (B group, n = 19) were analysed.

Results

During the second cycle, significantly decreased platelet aggregation was observed in the B group: 5 μM ADP (p = 0.0285, day 1 versus 8); 3.5 μM ADP (p = 0.0005, day 1 versus 8 and day 1 versus 11), collagen (p = 0.0014, day 4 versus 8, day 4 versus 11), 1.25 mg/ml ristocetin (p = 0.0017, day 1 versus 8 and day 1 versus 11). Agonist-induced platelet aggregation tended to be reduced over time during the 1st cycle in group B. In the thalidomide group, significant platelet aggregation inhibition by collagen only was found. Transient reduction in platelet count was observed in all patients, but more prominently in group B.

Conclusion

The inhibitory effects of prolonged exposure of bortezomib on platelet aggregation were demonstrated in relapsed/refractory MM patients, but antithrombotic activity of bortezomib should be clarified in further prospective studies.