These data demonstrate genetic heterogeneity in LVNC, with mutation of a novel gene, alpha-dystrobrevin, identified in LVNC associated with CHD. In addition, these results confirm that mutations in G4.5 result in a wide phenotypic spectrum of cardiomyopathies.
The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713; Exelon®), in patients with mild to moderately severe Alzheimer’s disease was evaluated in a 26-week open-label extension of a 26-week, double-blind, placebo-controlled study. By 52 weeks, patients originally treated with 6–12 mg/day rivastigmine had significantly better cognitive function than patients originally treated with placebo.
The intricate pathophysiology of brain disorders, difficult access to the brain, and the complexity and high risks and costs of drug development represent major hurdles for improving therapies. Nose-to-brain drug transport offers an attractive alternative or addition to formulation-only strategies attempting to enhance drug penetration into the CNS. Although still a matter of controversy, many studies in animals claim direct nose-to-brain transport along the olfactory and trigeminal nerves, circumventing the traditional barriers to CNS entry. Some clinical trials in man also suggest nose-to-brain drug delivery, although definitive proof in man is lacking. This review focuses on new nasal delivery technologies designed to overcome inherent anatomical and physiological challenges and facilitate more efficient and targeted drug delivery for CNS disorders.
BackgroundThere is a rising prevalence of excessive weight gain in pregnancy and an increasing number of pregnant women who are overweight or obese at the start of the pregnancy. Excessive weight gain during pregnancy is associated with adverse maternal and neonatal consequences and increases the risk of long-term obesity. Pregnancy therefore may be a key time to prevent excessive weight gain and improve the health of women and their unborn child. This systematic review sought to assess the effectiveness of behavioural interventions to prevent excessive weight gain in pregnancy and explore the factors that influence intervention effectiveness.MethodsWe undertook a systematic review of quantitative and qualitative evidence. This included a meta-analysis of controlled trials of diet and physical activity interventions to prevent excessive weight gain during pregnancy and a thematic synthesis of qualitative studies that investigated the views of women on weight management during pregnancy. A thorough search of eleven electronic bibliographic databases, reference lists of included studies, relevant review articles and experts in the field were contacted to identify potentially relevant studies.Two independent reviewers extracted data. RevMan software was used to perform the meta-analyses. Qualitative data was subject to thematic analysis. Both quantitative and qualitative data were aligned using a matrix framework.ResultsFive controlled trials and eight qualitative studies were included. The overall pooled effect size found no significant difference in gestational weight gain amongst participants in the intervention group compared with the control group (mean difference -0.28 95% CI -0.64 to 0.09). The study designs, participants and interventions all varied markedly and there was significant heterogeneity within this comparison in the meta-analysis (I2 67%). Subgroup and sensitivity analysis did not identify contextual elements that influenced the effectiveness of the intervention.In a thematic analysis of the qualitative studies, three major themes emerged relating to women's views of weight management in pregnancy: pregnancy as a time of transition and change, conflicting and contradictory messages and a perceived lack of control. When the results of both quantitative and qualitative data were aligned it was clear that some of the barriers that women described in achieving healthy weight gain in pregnancy were not addressed by the interventions evaluated. This may have contributed to the limited effectiveness of the interventions.ConclusionsDespite intense and often tailored interventions there was no statistically significant effect on weight gain during pregnancy. Inadequate and often contradictory information regarding healthy weight management was reported by women in qualitative studies and this was addressed in the interventions but this in itself was insufficient to lead to reduced weight gain. Multiple types of interventions, including community based strategies are needed to address this complex health pr...
EDS-FLU produces clinically and statistically significant improvement in all 4 diagnostically defining disease symptoms, polyp grade, and quality of life in patients with chronic rhinosinusitis with NPs.
We evaluated the efficacy and safety of the centrally acting cholinesterase inhibitor, rivastigmine tartrate, for patients with mild to moderately severe Alzheimer's disease (AD) with or without concurrent vascular risk factors (VRF). Patients (45-90 years of age) were randomized to placebo (n = 235), low-dose rivastigmine (1-4 mg/day, n = 233), or high-dose rivastigmine (6-12 mg/day, n = 231) for 26 weeks. Efficacy measures included the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), the Clinician's Interview Based Impression of Change (CIBIC-Plus), the Progressive Deterioration Scale (PDS), the Global Deterioration Scale (GDS), and the Mini-Mental State Examination (MMSE). For efficacy and safety analysis, patients were categorized by baseline Modified Hachinski Ischemic Score (MHIS) for the determination of VRF (MHIS > 0: presence of VRF; MHIS = 0: absence of VRF). As early as 12 weeks, the mean change from the baseline ADAS-Cog score was significantly different for those patients treated with high-dose rivastigmine compared with placebo controls in both MHIS categories. However, the treatment difference between high-dose rivastigmine and placebo at each time-point was larger for patients with MHIS > 0. The proportion of responders was significantly greater in the high-dose rivastigmine group for each level of improvement. No differences were noted between treatment groups regarding safety evaluations. Rivastigmine is effective in both categories of patients, and those with VRF experience greater clinical benefit (cognition, activities of daily living, and disease severity).
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