Long waiting period to enter methadone maintenance treatment: relation to patient characteristics and outcome

Methadone maintenance treatment is a chronic treatment for opiate addicts. After having reached full capacity, new admissions to our clinic were delayed (through a waiting list) for all but opiate addicts with HIV and pregnant women. We compared characteristics and outcomes between patients admitted without delay (1993-2002) and those admitted through a waiting list (2003-2009). All 704 patients admitted between June 1993 and June 2009 were followed up until June 2010. There were 470 patients in the early period and 234 in the late period (56 patients were admitted immediately and 178 after 1.1 ± 0.8 years of waiting). Predictors for 1-year retention in treatment (logistic regression model) were if a patient self-referred during the late period, on a waiting list. The waiting list patient group was characterized by older age and self-referral - two known independent predictors of better retention that were attributed to their superior retention rate.     

Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial

BACKGROUND: Intravenous immunoglobulin (IVIg) has been reported to reduce disease activity in patients with relapsing-remitting multiple sclerosis. We assessed the effect of IVIg treatment in patients after the first neurological event suggestive of demyelinative disease and evaluated the occurrence of a second attack and dissemination in time demonstrated by brain magnetic resonance imaging within the first year from onset. METHODS: We conducted a randomized, placebo-controlled, double-blind study in 91 eligible patients enrolled within the first 6 weeks of neurological symptoms. Patients were randomly assigned to receive IVIg treatment (2-g/kg loading dose) or placebo, with boosters (0.4 g/kg) given once every 6 weeks for 1 year. Neurological and clinical assessments were done every 3 months, and brain magnetic resonance imaging was performed at baseline and the end of the study. RESULTS: The cumulative probability of developing clinically definite multiple sclerosis was significantly lower in the IVIg treatment group compared with the placebo group (rate ratio, 0.36 [95% confidence interval, 0.15-0.88]; P = .03). Patients in the IVIg treatment group had a significant reduction in the volume and number of T2-weighted lesions and in the volume of gadolinium-enhancing lesions as compared with the placebo group (P = .01, P = .01, and P = .03, respectively). Treatment was well tolerated, compliance was high, and incidence of adverse effects did not differ significantly between groups. CONCLUSIONS: Intravenous immunoglobulin treatment for the first year from onset of the first neurological event suggestive of demyelinative disease significantly lowers the incidence of a second attack and reduces disease activity as measured by brain magnetic resonance imaging.     

Involvement of microparticles in diabetic vascular complications

Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and vascular complications. Circulating microparticles (MPs) are involved in thrombosis, inflammation, and angiogenesis. However, the role of MPs in T2DM vascular complications is unclear. We characterised the cell origin and pro-coagulant profiles of MPs obtained from 41 healthy controls and 123 T2DM patients with coronary artery disease, retinopathy and foot ulcers. The effects of MPs on endothelial cell coagulability and tube formation were evaluated. Patients with severe diabetic foot ulcers expressed the highest levels of MPs originated from platelet and endothelial cells and negatively-charged phospholipid-bearing MPs. MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor (TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients (<0.7) but high in patients with coronary artery disease and foot ulcers (>1.8, p≥0.002). MPs of all T2DM patients induced a more than two-fold increase in endothelial cell TF (antigen and gene expression) but did not affect TFPI levels. Tube networks were longest and most stable in endothelial cells that were incubated with MPs of healthy controls, whereas no tube formation occurred in MPs of diabetic patients with coronary artery disease. MPs of diabetic retinopathy and diabetic foot ulcer patients induced branched tube networks that were unstable and collapsed over time. This study demonstrates that MP characteristics are related to the specific type of vascular complications and may serve as a bio-marker for the pro- coagulant state and vascular pathology in patients with T2DM.     

Glutamate Toxicity to Differentiated Neuroblastoma N2a Cells Is Prevented by the Sesquiterpene Lactone Achillolide A and the Flavonoid 3,5,4′-Trihydroxy-6,7,3′-Trimethoxyflavone from <Emphasis Type="Italic">Achillea fragrantissima</Emphasis>

Glutamate toxicity is a major contributor to the pathophysiology of numerous neurodegenerative diseases including amyotrophic lateral sclerosis and Alzheimer’s disease. Therefore, protecting neuronal cells against glutamate-induced cytotoxicity might be an effective approach for the treatment of these diseases. We have previously purified from the medicinal plant Achillea fragrantissima two bioactive compounds which were not studied before: the sesquiterpene lactone achillolide A and the flavonoid 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TTF). We have shown that these compounds protect astrocytes from oxidative stress-induced cell death and inhibit microglial activation. The current study examined for the first time their effects on differentiated mouse neuroblastoma N2a cells and on glutamate toxicity. We have found that, although these compounds belong to different chemical families, they protect neuronal cells from glutamate toxicity. We further demonstrate that this protective effect might be, at least partially, due to inhibitory effects of these compounds on the levels of reactive oxygen species produced following treatment with glutamate.     

Dissociation Between Long-term Weight Loss Intervention and Blood Pressure: an 18-month Randomized Controlled Trial

BackgroundObesity is associated with elevated blood pressure (BP). In patients with obesity and hypertension, weight loss lowers BP, but the long-term effect of weight loss on BP is less clear.ObjectiveWe aimed to assess the effect of long-term weight loss intervention on BP in normotensive and hypertensive subjects.DesignRandomized controlled trial.ParticipantsTwo hundred seventy-eight subjects (mean age 47.9 ± 9.3 years, 89% male, 56% hypertensive) with abdominal obesity or elevated serum triglycerides and low high-density lipoprotein cholesterol were recruited.InterventionEighteen-month weight loss intervention.Main MeasuresBody weight and BP were measured at baseline, after 6 and 18 months.ResultsAfter 6 months of intervention, in the weight loss phase, body mass index (BMI) decreased by an average of −2.2±1.5 kg/m² (p<0.001) and both diastolic BP (DBP) and systolic BP (SBP) decreased by −2.1±8.8 mmHg and −2.3±12.9 mmHg, respectively (p<0.01 for both). The change in BMI was similar in normotensive and hypertensive subjects (−2.0±1.6 and −2.3±1.5, p = 0.246). However, DBP and SBP decreased significantly (−5.2±7.1 mmHg and −6.2±12.5 mmHg, respectively, p<0.001 for both) in hypertensive subjects, and increased in normotensive subjects (1.8±9.3 mmHg, p = 0.041 and 2.7±11.7 mmHg, p = 0.017, respectively). After 18 months, in the weight maintenance phase, BMI slightly increased (0.9±1.3 kg/m², p<0.001) but remained significantly lower than at baseline (p<0.0001). Unlike BMI, DBP and SBP increased significantly in hypertensive subjects (p<0.001) and returned almost to baseline levels.ConclusionWeight-loss intervention reduced BP in hypertensive patients, but this was not maintained in the long run.Clinical Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01530724","term_id":"NCT01530724"}}NCT01530724KEY WORDS: blood pressure, weight loss, body mass index, hypertension, randomized controlled trial