A double-blind placebo-controlled discontinuation study of zuclopenthixol for the treatment of aggressive disruptive behaviours in adults with mental retardation - secondary parameter analyses.

INTRODUCTION: Earlier studies showed risperidone to be effective in the treatment of aggression and self-injurious behaviour in adults with mental retardation but also having adverse side effects. This study was conducted to evaluate the effects of zuclopenthixol withdrawal. METHODS: After open treatment with zuclopenthixol (n=49) responders were randomly assigned to continue (n=19) or discontinue (n=20) zuclopenthixol treatment during a 12-week double-blind, placebo-controlled period. Effects were measured using the Disability Assessment Schedule (DAS), improvement on the Clinical Global Impression Scale (CGI-I), and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). RESULTS: Ten patients (20%) discontinued the study due to insufficient therapeutic effect or adverse events in the open period. EFFICACY: The superiority of zuclopenthixol over placebo among all randomized patients was supported not only by primary efficacy measure but also by the comparisons of mean scores of all secondary efficacy measures tested in a step-down-procedure (DAS, p<0.001; CGI-I, p<0.002, NOSIE, p<0.005). SAFETY: In both groups, one patient discontinued (5%) for adverse events. Adverse events were generally mild or moderate in severity. DISCUSSION: Zuclopenthixol proved to be safe and effective to keep a low rate of aggressive behaviour in adults with mental retardation.

Differences in urinary prothrombin fragment 1 + 2 levels after total hip replacement in relation to venous thromboembolism and bleeding events.

BACKGROUND: Prothrombin fragment 1 + 2 is excreted in urine (uF1 + 2) as a result of thrombin generation and, therefore, may be a useful marker of coagulation status. OBJECTIVES: To assess uF1 + 2 levels after total hip replacement (THR) in patients with venous thromboembolism (VTE) and bleeding events. PATIENTS/METHODS: This study was conducted in parallel with a prospective, dose-finding study evaluating the efficacy and safety of different doses of rivaroxaban (Xarelto, Bayer HealthCare AG, Wuppertal, Germany) for thromboprophylaxis, relative to enoxaparin. Deep vein thrombosis was diagnosed by mandatory venography performed 5-9 days after THR, or earlier if symptomatic. Symptomatic pulmonary embolism was diagnosed by objective testing. Bleeding complications were registered and stratified into major bleeding, clinically relevant, non-major bleeding, and minor bleeding, using predefined criteria. RESULTS: Eighty-four patients had a VTE and 57 patients had a bleeding event (n = 722). Significantly higher median uF1 + 2 levels were observed in the VTE group on day 3 after THR (P = 0.03), compared with control. Median uF1 + 2 levels were lower in the bleeding group on day 3 after THR (P = 0.005) and on the day of venography (P = 0.36), compared with control. Comparisons between the VTE and bleeding groups showed significantly lower median uF1 + 2 levels in the bleeding group on day 3 after THR and on the day of venography (P < 0.0001 and P = 0.006, respectively). CONCLUSIONS: Measurement of uF1 + 2 could provide a simple clinical test to evaluate non-invasively the intensity of coagulation activation after THR. However, further studies are required to confirm these encouraging preliminary results.

Fibrinogen in systemic lupus erythematosus: more than an acute phase reactant?

OBJECTIVE: To investigate whether plasma fibrinogen (FNG) measured longitudinally in a cohort of patients with systemic lupus erythematosus (SLE) increased over observational time faster than in a control group, and whether its increase might depend upon age, disease duration, disease activity, and medications. METHODS: Hospital based retrospective study with repeated measurements of plasma FNG and C-reactive protein (CRP) for patients and controls and erythrocyte sedimentation rate (ESR) and lupus activity index (LAI) for patients only. Study groups included patients with SLE: n = 96 (95% female), and healthy controls: n = 39 (95% female). Of the patients, 42% had SLE only, 23% had SLE with antiphospholipid antibodies (aPL), and 34% had SLE with aPL related thrombosis. RESULTS: Median baseline FNG was higher in patients (357 mg/dl; 95% CI 339-375) than in controls (271 mg/dl; 95% CI 251-291) by 86 mg/dl (95% CI 56-115, p < 0.001); in older subjects than younger (in patients and in controls); in patients with thrombosis than in other patient groups (by an average of 35 mg/dl; 95% CI 9-61 mg/dl): and in patients with longer disease duration (p = 0.05). Mean FNG increased faster in patients (19 mg/dl/year; 95% CI 12-26 mg/dl) than in controls (2.6 mg/dl/year; 95% CI 2.0-3.2 mg/dl). The increase was faster than the age effect and independent of patient group and disease activity. CONCLUSION: Plasma FNG in patients with SLE increases throughout followup regardless of disease activity, mimicking the age related increment observed in population based studies. The rapidity of the increment may reflect the prematurity of vascular disease typical of SLE.