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Cumulative Duration (cumulative + duration)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Neuropeptide Y suppresses absence seizures in a genetic rat model primarily through effects on Y2 receptors

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007
Margaret J. Morris
Abstract Neuropeptide Y (NPY) potently suppresses absence seizures in a model of genetic generalized epilepsy, genetic absence epilepsy rats of Strasbourg (GAERS). Here we investigated the Y-receptor subtype(s) on which NPY exerts this anti-absence effect. A dual in vivo approach was used: the cumulative duration of seizures was quantified in adult male GAERS in 90-min electroencephalogram recordings following intracerebroventricular (i.c.v.) injection of: (i) subtype-selective agonists of Y1 ([Leu31Pro34]NPY, 2.5 nmol), Y2 (Ac[Leu28,31]NPY24,36, 3 nmol), Y5 receptors [hPP1,17,Ala31,Aib32]NPY, 4 nmol), NPY (3 nmol) or vehicle; and following (ii) i.c.v. injection of antagonists of Y1 (BIBP3226, 20 nmol), Y2 (BIIE0246, 20 nmol) and Y5 (NPY5RA972, 20 nmol) receptors or vehicle, followed by NPY (3 nmol). Injection of the Y1 - and Y5 -selective agonists resulted in significantly less mean seizure suppression (37.4% and 53.9%, respectively) than NPY (83.2%; P < 0.05), while the Y2 agonist had similar effects to NPY (62.3% suppression, P = 0.57). Food intake was not increased following injection of the Y2 agonist, while significant increases in food intake were seen following NPY and the other Y-subtype agonists. Compared with vehicle, NPY injection suppressed seizures following the Y1 and Y5 antagonists (45.3% and 80.1%, respectively, P < 0.05), but not following the Y2 antagonist (5.1% suppression, P = 0.46). We conclude that NPY Y2 receptors are more important than Y1 and Y5 receptors in mediating the effect of NPY to suppress absence seizures in a genetic rat model. Y2 receptor agonists may represent targets for novel drugs against genetic generalized epilepsies without resulting in appetite stimulation. [source]

Pediatric Crohn's disease activity at diagnosis, its influence on pediatrician's prescribing behavior, and clinical outcome 5 years later

INFLAMMATORY BOWEL DISEASES, Issue 11 2009
Tamara Mesker MD
Abstract Background: No studies have been performed in which therapeutic regimens have been compared between mild and moderate-to-severe pediatric Crohn's disease (CD) at diagnosis. The aim was to analyze pediatric CD activity at diagnosis, its influence on pediatrician's prescribing behavior, and clinical outcome 5 years later. Methods: In a retrospective multicenter study we divided pediatric CD patients at diagnosis into mild or moderate-severe disease. We compared initial therapies, duration of first remission, number of exacerbations, height-for-age and weight-for-height evolvement, and cumulative duration of systemic steroid use in a 5-year follow-up period. Results: Forty-three children were included (25 with mild and 18 with moderate-severe disease). Aminosalicylate monotherapy was more frequently prescribed in the mild group (40% versus 17%; P < 0.01). The median duration of systemic steroid use was 18.3 months in the mild group and 10.4 months in the moderate-severe group (P = 0.09). Duration of first remission was 15.0 months in the mild group and 23.4 months in the moderate-severe group (P = 0.16). The mean number of exacerbations was 2.2 in the mild group and 1.8 in the moderate-severe group (P = 0.28). Conclusions: CD patients with mild disease were treated with aminosalicylate monotherapy more frequently. These patients, however, tend to have more exacerbations, shorter duration of first remission, and longer total duration of systemic steroid use. Our data support the concept that severity of disease at diagnosis does not reliably predict subsequent clinical course. This study suggests that there is no indication that children with mild CD should be treated differently compared to children with moderate-severe disease. (Inflamm Bowel Dis 2009) [source]

Estimation of time-dependent rate ratios in case-control studies: comparison of two approaches for exposure assessment,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2006
Geneviève Lefebvre
Abstract Purpose In pharmacoepidemiology, it is well recognized that the rate of adverse events may vary as a function of the cumulative duration of the drug exposure and/or the time since the end of the exposure. In case-control studies, two different approaches have been used to estimate temporal effects of drug exposure: the time-windows (T-Ws) approach and the duration-specific (D-S) approach. We decided to conduct a simulation study to compare the two approaches when the rate ratios (RRs) vary as a function of the cumulative duration of exposure and/or the time since the end of exposure. Methods We generated three cohorts of 500,000 individuals in which the rate of the event was varying as a function of the cumulative duration of exposure and the time since the end of exposure. For each cohort, a nested case-control analysis was performed using both the D-S and the T-Ws approaches. In the T-Ws approach, a RR is estimated within specific periods of time prior to the outcome, while a RR is estimated within periods of cumulative duration of exposure and time since the end of exposure in the D-S approach. Results We found that the RRs obtained from the D-S approach exactly corresponded to the RRs obtained from the cohort analyses, while the RRs obtained from the T-Ws approach generally not. RRs obtained from the T-Ws approach were difficult to interpret in terms of the effect of the duration and timing of the exposure. Conclusion The D-S approach should be used to investigate the duration-related effects of exposure in case-control studies. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Cancer risk in patients with rheumatoid arthritis treated with anti,tumor necrosis factor , therapies: Does the risk change with the time since start of treatment?

ARTHRITIS & RHEUMATISM, Issue 11 2009
Johan Askling
Objective To determine the short-term and medium-term risks of cancer in patients receiving anti,tumor necrosis factor , (anti-TNF,) therapies that have proven effective in the treatment of chronic inflammatory conditions. Methods By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. Results During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86,1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. Conclusion During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed. [source]