Pain due to osteoarthritis may impair the early outcome of deep brain stimulation in Parkinson's disease

Objective

To analyse postoperative pain due to osteoarthritis in patients with Parkinson's disease submitted to bilateral subthalamic nucleus stimulation.

Methods

Fifty-three parkinsonian patients (mean age, 59.9 ± 8.3 years; mean disease duration, 11.5 ± 4.2 years) referred for subthalamic nucleus stimulation were enrolled. Patients were prospectively asked to refer and describe any pain due to osteoarthritis they experienced at any time during the preoperative period and within the 6 postoperative months. Pre-existing pain due to osteoarthritis, therapeutic changes, parkinsonian motor disability and weight gain were assessed as explanatory factors for occurrence pain due to osteoarthritis after surgery.

Results

After surgery, thirty patients (57%) complained of pain due to osteoarthritis whereas all demonstrated great functional improvement. Twenty (67%) among the 30 experienced similar pain sensation before surgery. Symptoms occurred rapidly, between 4 and 26 postoperative weeks. Multiple stepwise regression analysis showed that pre-existing pain due to osteoarthritis, 6-month postoperative UPDRS III motor score and axial sub-score improvements in the off-drug/on-stimulation condition were accurate independent predictors of pain due to osteoarthritis after surgery (F(8, 41) = 2.20, p < 0.047).

Conclusion

Our results highlight the high prevalence of pain due to osteoarthritis arising shortly after subthalamic implantation. An accurate pain and osteo-articular assessment should be performed preoperatively in parkinsonian candidates for subthalamic nucleus stimulation in order to limit occurrence of complications in the early postoperative period.     

Development of the Little Developmental Coordination Disorder Questionnaire for preschoolers and preliminary evidence of its psychometric properties in Israel

Purpose

The early identification of motor coordination challenges before school age may enable close monitoring of a child's development and perhaps ameliorate some of the social, psychological and behavioral sequela that often accompany unrecognized Developmental Coordination Disorder (DCD). The purpose of this study was to develop and assess the initial psychometric properties of a screening tool, the Little DCD Questionnaire (Little DCDQ), designed to identify DCD amongst preschoolers aged 3 and 4.

Methods

The suitability of the items of the DCDQ’07 for 3- and 4-year-old children was assessed. Four items were found to be suitable and new items were generated. Content validity was ensured using a Table of Specification and the items were categorized into three sub-categories (Control During Movement, Fine Motor and General Coordination). The Little DCDQ was administered to 146 children (91 boys) aged 3 and 4 (mean age = 49.39 ± 7.16 months). Ninety-one typically developing children were included (mean age = 47.80 ± 7.05 months; 46 boys) while 55 children had been referred or were being treated for some form of developmental delay (mean age = 52.02 ± 6.60 months; 45 boys). Of this sample, 28 parents completed the questionnaire twice within a 2-week interval.

Results

Test-retest reliability was evidenced by moderate to good intraclass correlation coefficient values between scores on the two administrations for the total and the three sub-category scores. Evidence of internal consistency was provided by adequate to high Cronbach's alpha co-efficients calculated for each item, each sub-category score and the total score for the total group, and separately for the control group and the clinically referred group. Validity evidence based on relations to other variables was provided by the finding of significant group differences (clinically referred and control) for the total and sub-category scores for both the age groups and the total group.

Conclusions

Based on the preliminary psychometric evidence, it appears that the Little DCDQ meets many of the necessary standards for validity and reliability as a screening instrument, and shows promise as a useful clinical and research tool.     

Is the surgical repair of unruptured atherosclerotic aneurysms at a higher risk of intraoperative ischemia?

Background

The incidence of ischemia might be increased in the surgical repair of atherosclerotic unruptured aneurysms compared to non-atherosclerotic aneurysms. The atherosclerotic wall might increase the occurrence of thrombembolic events or its rigidity might endanger the occlusion of perforators within the aneurysm vicinity.

Methods

87 patients (53 patients without and 34 patients with atherosclerotic unruptured aneurysms, 50.5 ± 9.7 years) were analyzed for severity of atherosclerosis within the aneurysm and the aneurysm bearing vessel, surgical maneuvers, intraoperative alterations in evoked potentials and clinical and neuroradiological results.

Results

Temporary vessel occlusion (25% vs. 50%, p = 0.021), repositioning of a permanent clip (21% vs. 56%, p = 0.001) and aneurysm remnants (2% vs. 18%, p = 0.012) occurred more often in patients with atherosclerotic aneurysms. At 6 months, 3/34 patients with atherosclerosis (8.8%) had an unfavorable outcome, all patients without atherosclerosis had a favorable outcome (p = 0.056).

Conclusion

The surgical repair of unruptured aneurysms is safe but patients with atherosclerotic altered vessels and aneurysms accounted to a minor increase in unfavorable outcome and an increased risk of morbidity at 6 months postoperatively. This factor should be taken into consideration when performing surgery of atherosclerotic, unruptured aneurysms.     

The time-dependent change of insulin secretion in schizophrenic patients treated with olanzapine

The second generation antipsychotic drugs (SGAs) are effective in treating patients with schizophrenia and have been considered as the first line therapy. Recently, increasing attention has been drawn to the potential diabetogenic effect of these novel antipsychotics. The goal of this study was to evaluate the time-dependent effects of olanzapine treatment on pancreatic beta cell function in SGA-naïve schizophrenic patients. Forty-two schizophrenic subjects received olanzapine therapy for 8 weeks and thirty-three of them completed the trial. Of whom 33 completers (21 male, mean ± SD age: 37.6 ± 8.0 years) were inpatients and unexposed to SGA. The metabolic parameters were quantitatively assessed at weeks 0, 2, 4, and 8 by the intravenous glucose tolerance test. After 56-day olanzapine treatment, subjects had significant increases in body weight and as well as in the levels of triglyceride, total cholesterol, and low-density lipoprotein. Insulin secretion significantly decreased at week 2, returned to baseline at week 4, and significantly increased at week 8. Of the total samples, 18.2% and 33.3% of them met the criteria for significant weight gain and metabolic syndrome after 8-week olanzapine treatment, respectively. This study indicates that olanzapine-treated schizophrenic patients displayed biphasic changes in insulin secretion to a hyperglycemic challenge. The results of this study support that olanzapine might directly influence pancreatic beta cell function.     

Prolactin concentrations in newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis

Background

Previous studies have found increased prolactin concentrations in antipsychotic-naïve patients with schizophrenia. However, the roles of other hormones, and of potentially confounding variables such as gender and smoking, have not been considered.

Methods

Blood from newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis (13 women and 20 men) and matched controls (12 women and 21 men) was assayed for prolactin, as well as three other hormones that impact prolactin concentrations: thyrotropin-stimulating hormone (TSH), ghrelin, and cortisol.

Results

Patients had significantly higher prolactin concentrations: female patients had a mean [SD] of 37.1 ng/mL [24.9] vs. 13.5 ng/mL [7.2] for female control subjects (p = .001), while male patients had a mean of 15.3 ng/mL [9.5] vs. 7.6 ng/mL [2.2] for male control subjects (p = .006). Patients and control subjects did not differ on concentrations of TSH, ghrelin, or cortisol. The group differences could not be attributed to differences in age, gender, smoking, body mass index, ethnicity, or the socioeconomic status of the family of origin.

Conclusions

Increased prolactin concentrations in antipsychotic-naïve patients do not appear to be due to important confounding variables, or to the effects of elevated TSH, ghrelin, or cortisol.     

Enhanced platelet reactivity and thrombosis in Apoe-/- mice exposed to cigarette smoke is attenuated by P2Y12 antagonism

Introduction

Smoking increases the risk of acute arterial thrombosis, including myocardial infarction, likely due to multi-factorial effects on the vasculature. Heightened platelet reactivity may be among the adverse effects of smoke exposure.

Methods

To examine the effects of smoke exposure on platelet function in an atherosclerotic environment, Apoe-deficient female mice, maintained on a Western diet, were exposed (4 hrs/d, 5d/wk) to sidestream cigarette smoke in a whole-body exposure chamber for12 weeks. A separate group of wild type C57BL/6 J mice were also exposed to smoke in an identical fashion.

Results

In comparison to control Apoe-/- mice exposed to filtered ambient air, smoke-exposed Apoe-/- mice displayed a 1.8 ± 0.3 fold enhanced ADP-induced fibrinogen binding ex vivo (P < 0.001) and had a shorter time to thrombotic occlusion following ferric chloride injury of the carotid artery (median time to thrombosis of 8 vs. 13 min; P = 0.015). Administration of the direct-acting P2Y12 antagonist cangrelor blunted ex vivo fibrinogen binding and attenuated thrombosis (median time 20 min) in Apoe-/- mice exposed to sidestream smoke. The effects of smoke exposure required a proatherosclerotic background, as wild-type C57Bl/6 J mice exposed to smoke displayed similar fibrinogen binding and thrombotic occlusion times as did control mice.

Conclusions

Our results demonstrate that exposure to smoke heightens platelet reactivity and thrombosis in Apoe-/- mice and implicate signaling through platelet P2Y12 receptor as a mediator of the adverse consequence of smoke exposure. These results may partially explain the recent observations that smokers derive greater clinical benefit from the P2Y12 antagonist clopidogrel than do non-smokers.     

Catheter-directed ultrasound-accelerated thrombolysis for the treatment of acute pulmonary embolism

Background

Systemic thrombolysis rapidly improves right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) but is associated with major bleeding complications in up to 20%. The efficacy of low-dose, catheter-directed ultrasound-accelerated thrombolysis (USAT) on the reversal of RV dysfunction is unknown.

Materials and methods

We performed a retrospective analysis of 24 PE patients (60 ± 16 years) at intermediate (n = 19) or high risk (n = 5) from the East Jefferson General Hospital who were treated with USAT (mean rt-PA dose 33.5 ± 15.5 mg over 19.7 hours) and received multiplanar contrast-enhanced chest computed tomography (CT) scans at baseline and after USAT at 38 ± 14 hours. All CT measurements were performed by an independent core laboratory.

Results

The right-to-left ventricular dimension ratio (RV/LV ratio) from reconstructed CT four-chamber views at baseline of 1.33 ± 0.24 was significantly reduced to 1.00 ± 0.13 at follow-up by repeated-measures analysis of variance (p < 0.001). The CT-angiographic pulmonary clot burden as assessed by the modified Miller score was significantly reduced from 17.8 ± 5.3 to 8.7 ± 5.1 (p < 0.001). All patients were discharged alive, and there were no systemic bleeding complications but four major access site bleeding complications requiring transfusion and one suspected recurrent massive PE event.

Conclusions

In patients with intermediate and high risk PE, low-dose USAT rapidly reverses right ventricular dilatation and pulmonary clot burden.     

Patients with primary antiphospholipid antibody syndrome and without associated vascular risk factors present a normal endothelial function

Introduction

Primary antiphospholipid antibody syndrome (PAPS) is characterized by venous or arterial thrombosis and positive antiphospholipid antibodies. It is controversial whether PAPS patients have early atherosclerosis. Endothelial dysfunction is an early event in the natural history of atherosclerosis. Aim of our study was to compare endothelial function of patients with PAPS and no associated risk factors with that of age- and sex-matched controls.

Materials and Methods

Patients with PAPS, carefully selected to exclude all known risk factors for cardiovascular diseases, estrogen therapy, pregnancy, intake of drugs affecting endothelial function, vitamins or antioxidants, were included in a case-control study. Controls were age- (± 5 years) and sex-matched subjects with the same exclusion criteria but without PAPS. Flow-mediated dilation of the brachial artery and some plasmatic markers of endothelial and platelet activation were measured. Measures are expressed as mean±SEM.

Results

Twenty cases (mean age 42 ± 4.0 years, 11 females) and 39 controls (mean age 41 ± 2.9, 22 females) were studied. FMD was 5.7 ± 0.8% in cases (95% CI: 4.1 to 7.3) and 6.8 ± 0.5% (5.7 to 7.9) in controls (p = NS). Plasma von Willebrand factor was 128 ± 11.3% and 134.2 ± 16.1% in cases and controls, respectively (p = NS). Soluble P-selectin and soluble CD40L were 94.1 ± 4.9 ng/ml and 0.7 ± 0.1 ng/ml in cases and 87.7 ± 4.0 ng/ml and 1.0 ± 0.2 in controls, respectively (p = NS). In a substudy, circulating progenitor and mature endothelial cells were comparable between the two groups.

Conclusions

Endothelial function in patients with PAPS and no associated risk factors is similar to that of age- and sex- matched controls. These data suggest that the alterations leading to thrombosis in PAPS concern primarily the clotting system.     

Factor XII Ofunato: Lys346Asn mutation associated with blood coagulation factor XII deficiency causes impaired secretion through a proteasome-mediated degradation

Introduction

Congenital blood coagulation factor XII (FXII) deficiency is a rare coagulation disease and an autosomal recessive trait. It is found by chance in many cases. We identified a novel mutation (Lys346Asn) in the FXII gene of a patient with FXII deficiency, designated as Factor XII Ofunato.

Methods

The proband was a 75-year-old Japanese woman with a prolonged activated partial thromboplastin time (52.8 s). The FXII activity and antigen were greatly reduced (activity, 5%; antigen, 4.5%). We analyzed FXII gene of this patient using a direct sequencing method and characterized mutant FXII through in vitro expression studies.

Results

Sequence analysis of the FXII gene revealed a G → C point mutation at nucleotide 9845, resulting in Lys346 (AAG) → Asn (AAC) replacement in the catalytic domain. Expression studies in Chinese hamster ovary cells demonstrated that mutant FXII (346 N-FXII) showed a lower level of accumulation in the cells than wild-type. Secretion of 346 N-FXII was greatly reduced in culture medium. We also investigated mRNA expression levels of wild-type and 346 N-FXII in transfected cells using quantitative RT-PCR. Both mRNA expressions were equivalent levels. Pulse-chase experiments showed that 346 N-FXII was extensively degraded intracellularly compared to wild-type. Using membrane-permeable inhibitors, we observed that degradation occurred in the pre-Golgi compartment and that proteasome apparently plays a central role in this process.

Conclusions

These results show that most 346 N-FXII is degraded intracellularly through endoplasmic reticulum-associated degradation as the protein quality control system, resulting in an insufficient secretion phenotype.     

Extracorporeal cardiopulmonary support may be an efficient rescue of patients after massive pulmonary embolism. An experimental porcine study

Introduction

Treatment of massive pulmonary embolism leading to cardiac arrest is controversial but restitution of circulation within a shorter time is crucial. Cardiopulmonary support and therapeutic hypothermia is an option for cardiac arrest and could be used to treat massive PE. However, hypothermia may influence the effect of the ongoing intrinsic fibrinolysis.

Objectives

To establish a porcine model of massive pulmonary embolism, to show that cardiopulmonary support can rescue pigs with massive pulmonary embolism and to examine the effect of hypothermia on fibrinolysis.

Methods

Pigs ~ 80 kg were anesthetised and prepared for cardiopulmonary support. Repetitive injections of preformed blood thrombi into the right atrium were done until cardiac arrest. Cardiopulmonary support was established and eighteen pigs were randomised into 3 groups: Normothermia (38-39 °C); hypothermia (33-34 °C); or medication with recombinant tissue plasminogen activator. After three hours the pigs were weaned from cardiopulmonary support, and after 15 minutes with spontaneous circulation assassinated and autopsied. Remaining thrombi in the lungs were weighed.

Results

The development of fatal pulmonary embolism was highly reproducible. All 18 pigs could be weaned from cardiopulmonary support and survived more than 15 minutes. The amount of remaining thromboemboli was substantial in all groups and not significantly different between groups. Normothermic group 20.0 ± 2.2 g, Hypothermic group 17.0 ± 3.7 g, and rt-PA group 14.3 ± 3.2 g.

Conclusions

Cardiopulmonary support could rescue pigs with massive pulmonary embolism. Hypothermia did not reduce the emboli but may for other reasons be beneficial. The optimal additional treatment is still unknown but treatment modalities can be tested in this model.     

The effect of clopidogrel besylate and clopidogrel hydrogensulfate on platelet aggregation in patients with coronary artery disease: a retrospective study

Background

Recently several alternative forms of the original clopidogrel hydrogensulfate (CHS) were spread worldwide. A large amount of such drugs turned out to be clopidogrel besylate (CB). Only three studies, involving healthy volunteers, investigated the antiplatelet effect of CB, whereas its attribute remained unexplored in the case of patients with cardiovascular diseases. This retrospective study aimed to evaluate the difference between the antiplatelet effects of two clopidogrel formulas, CHS and CB, on patients with coronary artery diseases.

Methods

Data of 150 patients with previous CHS treatment were investigated. According to the documentations, the CHS therapy was shifted to CB. 94 patients of the selected population received dual antiplatelet therapy, clopidogrel and aspirin. The antiplatelet effects of CHS and CB were compared by ADP induced platelet aggregation measurements using light transmission aggregometry.

Results

Irrespective of the therapeutic combinations the performed statistical investigations failed to show significant difference (p = 0.30) between the effect of CB (AGGmax_CB: 27.6 ± 13.7%) or CHS (AGGmax_CHS: 29.0 ± 15.3%) on the ADP induced platelet aggregation. Insignificant deviations were found in both forms of clopidogrel salts, either in the lack (AGGmax_CB : 32.5 ± 14,2%; AGGmax_CHS: 34,0 ± 16,1%; p = 0,29) or in the presence of aspirin (AGGmax_CB: 24.7 ± 12,5%; AGGmax_CHS: 26,0 ± 14,1%; p = 0,31).

Conclusion

Our results indicated that both CB and CHS had an identical inhibitory effect on ADP induced platelet aggregation in patients with cardiovascular diseases. Moreover their efficiency showed no overall significant difference in the case of dual antiplatelet therapy with aspirin as well. However there might be an inter- and intraindividual variability between the two clopidogrel formulas.     

A randomised study comparing the antiplatelet and antinflammatory effect of clopidogrel 150 mg/day versus 75 mg/day in patients with ST-segment elevation acute myocardial infarction and poor responsiveness to clopidogrel: Results from the DOUBLE study

Introduction

The antiplatelet effect of standard or increased clopidogrel doses in patients with ST- segment elevation acute myocardial infarction (STEMI) has never been studied. In this study we compared the antiplatelet effect of a 75 mg daily maintenance dose of clopidogrel with 150 mg in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

Materials and methods

Fifty-four patients with STEMI undergoing PCI were randomly allocated to receive either 75 mg/day clopidogrel (group 1) or 150 mg/day (group 2) for 1 month. Platelet function, measured by 5 different assays, was determined at 3 time points: 38 ± 8 hours after the procedure, 1 week and 1 month after randomization.

Results

In group 1, mean ± SD platelet reactivity index (PRI) measured with the VASP assay was 57.7 ± 15.7% and 46.9 ± 15.7% at 1 week and 1 month, respectively, compared to 38.8 ± 15.7% and 34.9 ± 12.6% in group 2 (p = 0.0001). Same results were observed for light transmittance aggregometry, whole blood aggregometry and VerifyNow, but not for thromboelastometry. In contrast to what may be expected, the 75 mg daily maintenance dose took longer than 1-week to provide the full clopidogrel antiplatelet effect. Furthermore, patients in group 2 had a nearly 50% reduction in C-reactive protein levels both at 1 week and 1 month.

Conclusion

In patients with STEMI and poor responsiveness to clopidogrel a 150 mg daily maintenance dose of clopidogrel is associated with a significant reduction of platelet aggregation and a trend towards reduced inflammation.     

Increased thrombin generation in inflammatory bowel diseases

Background

Inflammatory bowel diseases (IBD) are characterized by an increased thrombotic risk of uncertain etiology. Endogenous thrombin potential (ETP), a parameter of the thrombin generation curve, represents a new tool in the evaluation of thrombotic and bleeding disorders.

Aims

To study ETP in IBD patients and to correlate the results with clinical and biochemical features.

Methods

Seventy-four IBD patients (37 ulcerative colitis and 37 Crohn's disease) and 74 sex- and age-matched healthy individuals. ETP was measured upon activation of coagulation with small amounts of tissue factor and phospholipids in the presence or absence of thrombomodulin; results were expressed as nM thrombin·minutes.

Results

Mean±SD ETP values were significantly higher in patients (1,499 ± 454) than controls (1,261 ± 385) (p < 0.001) only when the test was performed in the presence of thrombomodulin. ETP evaluated as ratio (with/without thrombomodulin), taken as an index of hypercoagulability, was significantly higher in patients (0.69 ± 0.14) than controls (0.62 ± 0.18) (p < 0.006). Patients with increased C-reactive protein (CRP) had significantly higher mean ETP (1,721 ± 458) than those with normal CRP (1,357 ± 394) or controls (1,261 ± 385) (p < 0.001). Patients who at the time of blood sampling were classified as having a clinically active disease had ETP higher than those who were quiescent (1,655 ± 451 versus 1,388 ± 427, p < 0.001) or controls (1,261 ± 385, p < 0.001).

Conclusions

ETP measured in the presence of thrombomodulin or as ratio (with/without thrombomodulin) is increased in IBD patients, mainly in those with increased CRP or active disease. It may be considered as a candidate test for prospective studies aimed at assessing the risk of thrombosis in IBD patients.     

Effectiveness of lamotrigine in bipolar disorder in a clinical setting

Objective

To assess lamotrigine effectiveness in bipolar disorder (BD) patients in a clinical setting.

Method

Open lamotrigine was naturalistically administered to outpatients at the Stanford University BD Clinic assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.

Results

One hundred and ninety-seven patients (64 BD I, 110 BD II, 21 BD NOS, 2 Schizoaffective Bipolar Type, mean ± SD age 42.2 ± 14.4 years, 62% female) had 200 trials of lamotrigine. Lamotrigine was combined with a mean of 2.1 ± 1.5 other psychotropic medications, most often during euthymia or depressive symptoms. Mean lamotrigine duration was 434 ± 444 days, and mean final dose was 236 ± 132 mg/day without valproate, and 169 ± 137 mg/day with valproate. Lamotrigine was discontinued in only 26.5% of trials at 255 ± 242 days, most often due to inefficacy, and seldom due to adverse effects. In 31.5% of trials lamotrigine was continued 264 ± 375 days with no subsequent psychotropic added. In 42.0% of trials lamotrigine was continued 674 ± 479 days, but had subsequent psychotropic added at 146 ± 150 days, most often for anxiety/insomnia and depressive symptoms. In 145 trials started at Stanford, lamotrigine primarily yielded relief of depressive symptoms or maintained euthymia. In 55 trials in which lamotrigine was started prior to Stanford, lamotrigine primarily maintained euthymia. Lamotrigine was generally well tolerated, with no serious rash, and only 3.5% discontinuing due to benign rash.

Conclusion

In a cohort of bipolar disorder outpatients commonly with comorbid conditions, and most often receiving complex combination therapy, lamotrigine had a low (26.5%, with an overall mean duration of treatment of 434 days) discontinuation rate, suggesting effectiveness in BD in a clinical setting.     

Impaired spontaneous thrombolytic activity measured by global thrombosis test in males with metabolic syndrome

Introduction

In patients with metabolic syndrome (MetS), activity of the fibrinolytic system is generally surmised to be decreased through increased plasminogen activator inhibitor-1 (PAI-1) generation. However, there have been no detailed reports describing whether the clot lysis activity is more dominant than increased clot formation activity for production of the thrombotic state in MetS.

Methods

The global thrombosis test (GTT) is a novel method designed to test both clot formation and clot lysis activities under physiological conditions by using non-anticoagulated blood samples in vitro. We used the GTT to examine the thrombotic or thrombolytic states in males with MetS.

Results

Lysis time, which reflects spontaneous clot lysis activity, was significantly longer in MetS subjects (median, 1494 s; range, 865-3596 s; n = 30) than in control subjects (median 1246 s; range, 667-2239 s; n = 53). There was no significant difference between the two groups in occlusion time, which reflects platelet function. The mean level of PAI-1 was significantly higher in MetS subjects than in controls (mean ± SE, 8.7 ± 1.1 and 5.0 ± 0.5 ng/mL, respectively). PAI-1 level and lysis time were significantly correlated (r = 0.400, P < 0.01).

Conclusion

These results suggest that male patients with MetS are more likely than controls to experience a thrombotic state through decreased fibrinolytic activity due to increased PAI-1 generation, and that the GTT is useful for evaluating fibrinolytic activity in vitro.     

Psychopharmacological comparison of schizophrenia spectrum disorder with and without cannabis dependency

Background

Although incidence of schizophrenia is higher among cannabis users and marijuana is the most common abused drug by adolescents, etiological linkage between schizophrenia and cannabis use is still not clarified. Clinical experiences suggest that regular cannabis user can show similar psychotic episode to schizophrenic disorders but it is still unclear if chronic cannabis use with schizophreniform disorder is a distinct entity requiring special therapy or it can be treated as classical schizophrenia. There are no data available on the comparison of pharmacotherapy between schizophreniform patients with and without cannabis use.

Methods

Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Comparison of anamnesis, family history, social-demographic condition, positive and negative symptoms, acute and long-term therapies recorded by clinical interviews was performed with chi square tests, logistic binary regression and t-tests using SPSS 13.0 for Windows software.

Results

Men were over-represented in cannabis dependent group while mean age was lower among them compared to Cnbs0 subgroup. Prevalence of suicidal attempt was increased in men without cannabis use (OR = 5.25, p = 0.016). Patients without cannabis use spent more time in hospital (p = 0.026) and smoking was more frequent among them (OR = 1.36, p = 0.047). The chance to get olanzapine for acute therapy and aripiprazol for long term therapy was more than two fold in Cnbs1 subgroup (OR = 2.66, OR = 3.67, respectively). However, aripiprazol was used for acute therapy with significantly lower risk in Cnbs1 subgroup (OR = 0.47, p = 0.023). Olanzapine was administered for long term therapy in a higher dose to Cnbs0 patients (p = 0.040). Also higher dose of risperidon LAI was used in women without cannabis dependency compared to women of Cnbs1 subgroup (p = 0.020). Positive and negative symptoms and family history did not differ significantly between the two subgroups.

Conclusion

Although symptom profile was similar, hospitalization time, suicidal anamnesis, smoking habit and also dosage, intensity and lasting of therapy were different between the two subgroups. Further prospective studies are required for the investigation of the clinical and molecular background of this discrepancy in order to determine a relevant protocol of prevention and treatment of the chronic cannabis use related psychotic disorder.     

Accuracy of a portable international normalized ratio monitor for patients receiving a low molecular weight heparin as a bridge pending full oral anticoagulant efficacy

Background

Point of care (POC) devices measuring the international normalized ratio (INR) are accurate for patients with stable disease, but their efficiency has not been prospectively assessed during the “bridging period” when patients are receiving a low molecular weight heparin (LMWH) on top of a vitamin K antagonist (VKA) until the target INR is reached.

Methods

188 dual INR measurement using the POC (INR_POC) and the laboratory (INR_lab) at the same time were consecutively determined : 69 in patients receiving LMWH + VKA (bridging group) and 119 in patients receiving only a VKA (control group). INRpoc was compared to INR_lab.

Results

Test strip failure rate was higher in the bridging group than in the control group (29% vs 4% ; p < 0,001).In successful tests, POC accuracy was not modified by LMWH administration: the correlation coefficients between POC and lab INR values for the bridging group and the control group were 0,81 and 0,87 respectively, and the relative measure of divergence (RMD = INR_lab - INR_poc / INR_lab) was lower in the bridging group than in the control group (4 ± 7% vs 10 ± 14%; p = 0,02). Finally, clinically relevant agreement between POC and laboratory was of 90% in the bridging group and 92.1% in the control group (p = 0.6).

Conclusion

With the POC used (INRatio), in patients receiving LMWH when the POC gives a result, it is as accurate as in patients not receiving a LMWH.     

Changes in plasma von Willebrand factor and ADAMTS13 levels associated with left atrial remodeling in atrial fibrillation

Introduction

Previous studies have shown raised plasma von Willebrand factor (VWF) levels in patients with atrial fibrillation (AF). However, little is known about changes of VWF associated with VWF-cleaving protease (ADAMTS13) in AF. The aim of this study was to examine the relationship between changes in plasma VWF and ADAMTS13 levels, and left atrial remodeling in AF patients.

Materials and Methods

We measured plasma VWF and ADAMTS13 antigen levels in 70 paroxysmal AF (PAF) patients, 56 chronic AF (CAF) patients, and 55 control subjects.

Results

Plasma VWF levels (mU/ml) were significantly higher in CAF and PAF patients compared with the controls (2103 ± 743, 1930 ± 676, 1532 ± 555, respectively, P < 0.0001 in CAF vs. controls, P = 0.001 in PAF vs. control), while ADAMTS13 levels (mU/ml) were significantly lower in CAF and PAF patients compared with the controls (795 ± 169, 860 ± 221, 932 ± 173, respectively, P = 0.0002 in CAF vs. controls, P = 0.04 in PAF vs. control). The VWF/ADAMTS13 ratio was significantly higher in patients with CAF than PAF or controls (2.81 ± 1.30, 2.34 ± 0.92, 1.73 ± 0.83, respectively; P = 0.01 in CAF vs. PAF, P < 0.0001 in CAF vs. controls). There was a significant correlation between the VWF/ADAMTS13 ratio and left atrial diameter (positive correlation; r = 0.275, P = 0.0002) and left atrial appendage flow velocity (negative correlation; r = - 0.345, P = 0.0018).

Conclusions

These findings suggest that the imbalance between plasma VWF and ADAMTS13 levels caused by left atrial remodeling might be closely associated with intra-atrial thrombus formation in AF patients.     

Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: A prospective multicenter survey

Introduction

Although supplementation with antithrombin (AT) concentrates has been widely accepted for the treatment of disseminated intravascular coagulation (DIC) in Japan, the effects and adverse effects have not been investigated.

Materials and Methods

We conducted a nonrandomized multi-institutional survey. A total of 729 septic DIC patients with AT activity levels of 70% or lower, who had undergone AT substitution at either 1500 IU/day or 3000 IU/day for consecutive 3 days were analyzed. Of these, 650 and 79 patients had received 1500 IU/day (AT1500 group) and 3000 IU/day (AT3000 group), respectively.

Results

Bleeding events were observed in 6.52% of patients (severe bleeding, 1.71%). A significant decrease in initial AT level (below 50%) was observed in 69.6% of patients in AT3000 group and 48.2% in AT1500 group, and this difference was significant (P < 0.01). A logistic-regression analysis conducted using age, gender, body weight, initial AT activity, and supplemented AT dose, revealed that higher initial AT activity (odds ratio (OR), 1.032; P < 0.001), AT dose of 3000 IU/day (OR, 1.912; P = 0.026), and age (OR, 0.985; P = 0.023) were significant factors for improved survival.

Conclusion

The risk of severe bleeding is less than 2%, and concomitant administration of heparin did not increase the risk. The survival in AT1500 group was 65.2%, while that in AT3000 group was 74.7%.