Efficacy and safety profiles of manidipine compared with amlodipine: A meta-analysis of head-to-head trials

The aim of this meta-analysis was to compare the efficacy and safety profile of manidipine 20 mg with that of amlodipine 10 mg. A systematic research of quantitative data produced or published between 1995 and 2009 was performed. Head-to-head randomized controlled trials (RCTs) of 12 months minimum duration reporting comparative efficacy (changes in systolic and diastolic blood pressure) and safety (total adverse events and ankle oedema), were included. Four high-quality RCTs, accounting for 838 patients (436 received manidipine and 402 received amlodipine) were included. The effi cacy of manidipine and amlodipine was statistically equivalent: effect size for DBP =−0.08 (p = 0.22) and SBP =−0.01 (p =0.83).The global safety of manidipine was signifi cantly better than amlodipine: the relative risk (RR) for adverse event was 0.69 (0.56 – 0.85), and particularly for ankle oedema RR was 0.35 (0.22 – 0.54). Publication bias was not signifi cant and the robustness of the analyses was good. These data suggest a better efficacy/safety ratio of manidipine over amlodipine

Structural correlations in bacterial metabolic networks

<p>Abstract</p> <p>Background</p> <p>Evolution of metabolism occurs through the acquisition and loss of genes whose products acts as enzymes in metabolic reactions, and from a presumably simple primordial metabolism the organisms living today have evolved complex and highly variable metabolisms. We have studied this phenomenon by comparing the metabolic networks of 134 bacterial species with known phylogenetic relationships, and by studying a neutral model of metabolic network evolution.</p> <p>Results</p> <p>We consider the 'union-network' of 134 bacterial metabolisms, and also the union of two smaller subsets of closely related species. Each reaction-node is tagged with the number of organisms it belongs to, which we denote organism degree (OD), a key concept in our study. Network analysis shows that common reactions are found at the centre of the network and that the average OD decreases as we move to the periphery. Nodes of the same OD are also more likely to be connected to each other compared to a random OD relabelling based on their occurrence in the real data. This trend persists up to a distance of around five reactions. A simple growth model of metabolic networks is used to investigate the biochemical constraints put on metabolic-network evolution. Despite this seemingly drastic simplification, a 'union-network' of a collection of unrelated model networks, free of any selective pressure, still exhibit similar structural features as their bacterial counterpart.</p> <p>Conclusions</p> <p>The OD distribution quantifies topological properties of the evolutionary history of bacterial metabolic networks, and lends additional support to the importance of horizontal gene transfer during bacterial metabolic evolution where new reactions are attached at the periphery of the network. The neutral model of metabolic network growth can reproduce the main features of real networks, but we observe that the real networks contain a smaller common core, while they are more similar at the periphery of the network. This suggests that natural selection and biochemical correlations can act both to diversify and to narrow down metabolic evolution.</p

Resource distributions affect social learning on multiple timescales

We study how learning is shaped by foraging opportunities and self-organizing processes and how this impacts on the effects of “copying what neighbors eat” on multiple timescales. We use an individual-based model with a rich environment, where group foragers learn what to eat. We vary foraging opportunities by changing local variation in resources, studying copying in environments with pure patches, varied patches, and uniform distributed resources. We find that copying can help individuals explore the environment by sharing information, but this depends on how foraging opportunities shape the learning process. Copying has the greatest impact in varied patches, where local resource variation makes learning difficult, but local resource abundance makes copying easy. In contrast, copying is redundant or excessive in pure patches where learning is easy, and mostly ineffective in uniform environments where learning is difficult. Our results reveal that the mediation of copying behavior by individual experience is crucial for the impact of copying. Moreover, we find that the dynamics of social learning at short timescales shapes cultural phenomena. In fact, the integration of learning on short and long timescales generates cumulative cultural improvement in diet. Our results therefore provide insight into how and when such processes can arise. These insights need to be taken into account when considering behavioral patterns in nature

Effectiveness and cost-effectiveness of a patient-initiated botulinum toxin treatment model for blepharospasm and hemifacial spasm: a study protocol for a randomised controlled trial

Background Blepharospasm and hemifacial spasm are debilitating conditions that significantly impact on patient quality of life. Cyclical treatment with botulinum toxin injections offers temporary relief, but the duration of treatment efficacy is variable. The standard model of patient care defines routine fixed-time based scheduled treatment cycles which may lead to unnecessarily frequent treatment for some patients and experience of distressing symptoms in others, if symptoms return before the scheduled follow-up period. Methods/Design A randomised controlled trial will compare a patient-initiated model of care, where patients determine botulinum toxin treatment timing, to the standard model of care in which care is scheduled by the clinical team. A sample of 266 patients with blepharospasm or hemifacial spasm will be recruited from Moorfields Eye Hospital (MEH), London. The trial will be accompanied by a mixed methods evaluation of acceptability of the new service. Patients who meet eligibility criteria will be assessed at baseline and those in the intervention group will be provided instructions on how to book their own treatment appointments. Patients in both groups will be followed up 3 and 9 months into the trial and all patients will be returned to usual care after 9 months to meet safety protocols. Primary outcome measures include disease severity (questionnaire), functional disability (questionnaire) and patient satisfaction with care (questionnaire). Secondary outcomes include disease-specific quality of life (questionnaire), mood (questionnaire), illness and treatment perceptions (questionnaire and semi-structured interviews), economic impact (questionnaire) and acceptability (questionnaire and semi-structured interviews). Discussion This trial will assess the effectiveness and cost-effectiveness of a patient-led care model for botulinum toxin therapy. If the new model is shown to be effective in reducing distress and disability in these populations and is found to be acceptable to patients, whilst being cost-effective, this will have significant implications for service organisation across the NHS. Trial registration UK Clinical Research Network (UKCRN) Portfolio 18660. Clinicaltrials.gov ID NCT102577224 (registered 29th October 2015

The role of parenting behaviors in childhood post-traumatic stress disorder: a meta-analytic review

Studies that have examined the association between parenting behaviors and childhood post-traumatic stress disorder (PTSD) have yielded mixed findings. To clarify the role of parenting in childhood PTSD we conducted a systematic review and meta-analysis of 14 studies that investigated the association between parenting and youth PTSD symptoms (total n = 4010). Negative parenting behaviors (e.g. overprotection, hostility) accounted for 5.3% of the variance in childhood PTSD symptoms. Positive parenting behaviors (e.g. warmth, support) account for 2.0% of variance. The negative and positive parenting and child PTSD symptom associations did not statistically differ in magnitude. Moderator analyses indicated that methodological factors and trauma variables may affect the association between parenting and child PTSD. Most studies relied upon questionnaire measures of general parenting style, and studies were predominantly cross-sectional with weaker evidence found in longitudinal studies. Given the small number of high quality studies available, only provisional recommendations about the role of parenting in childhood PTSD are made

Exercise and global well-being in community-dwelling adults with fibromyalgia: a systematic review with meta-analysis

<p>Abstract</p> <p>Background</p> <p>Exercise has been recommended for improving global-well being in adults with fibromyalgia. However, no meta-analysis has determined the effects of exercise on global well-being using a single instrument and when analyzed separately according to intention-to-treat and per-protocol analyses. The purpose of this study was to fill that gap.</p> <p>Methods</p> <p>Studies were derived from six electronic sources, cross-referencing from retrieved studies and expert review. Dual selection of randomized controlled exercise training studies published between January 1, 1980 and January 1, 2008 and in which global well-being was assessed using the Fibromyalgia Impact Questionnaire (FIQ) were included. Dual abstraction of data for study, subject and exercise program characteristics as well as assessment of changes in global well-being using the total score from the FIQ was conducted. Risk of bias was assessed using the Cochrane bias assessment tool. Random-effects models and Hedge's standardized effect size (<it>g</it>) were used to pool results according to per-protocol and intention-to-treat analyses.</p> <p>Results</p> <p>Of 1,025 studies screened, 7 representing 5 per-protocol and 5 intention-to-treat outcomes in 473 (280 exercise, 193 control) primarily female (99%) participants 18-73 years of age were included. Small, statistically significant improvements in global well-being were observed for per-protocol (<it>g </it>and 95% confidence interval, -0.39, -0.69 to -0.08) and intention-to-treat (-0.34, -0.53 to -0.14) analyses. No statistically significant within-group heterogeneity was found (per-protocol, Q_w= 6.04, <it>p </it>= 0.20, <it>I</it>²= 33.8%; intention-to-treat, Q_w= 3.19, <it>p </it>= 0.53, <it>I</it>²= 0%) and no between-group differences for per-protocol and intention-to-treat outcomes were observed (Q_b= 0.07, <it>p </it>= 0.80). Changes were equivalent to improvements of 8.2% for per-protocol analyses and 7.3% for intention-to-treat analyses.</p> <p>Conclusions</p> <p>The results of this study suggest that exercise improves global well-being in community-dwelling women with fibromyalgia. However, additional research on this topic is needed, including research in men as well as optimal exercise programs for improving global well-being in adults.</p

Computer Therapy for the Anxiety and Depressive Disorders Is Effective, Acceptable and Practical Health Care: A Meta-Analysis

Background: Depression and anxiety disorders are common and treatable with cognitive behavior therapy (CBT), but access to this therapy is limited. Objective: Review evidence that computerized CBT for the anxiety and depressive disorders is acceptable to patients and effective in the short and longer term. Method: Systematic reviews and data bases were searched for randomized controlled trials of computerized cognitive behavior therapy versus a treatment or control condition in people who met diagnostic criteria for major depression, panic disorder, social phobia or generalized anxiety disorder. Number randomized, superiority of treatment versus control (Hedges g) on primary outcome measure, risk of bias, length of follow up, patient adherence and satisfaction were extracted. Principal Findings: 22 studies of comparisons with a control group were identified. The mean effect size superiority was 0.88 (NNT 2.13), and the benefit was evident across all four disorders. Improvement from computerized CBT was maintained for a median of 26 weeks follow-up. Acceptability, as indicated by adherence and satisfaction, was good. Research probity was good and bias risk low. Effect sizes were non-significantly higher in comparisons with waitlist than with active treatment control conditions. Five studies comparing computerized CBT with traditional face-to-face CBT were identified, and both modes of treatment appeared equally beneficial. Conclusions: Computerized CBT for anxiety and depressive disorders, especially via the internet, has the capacity to provide effective acceptable and practical health care for those who might otherwise remain untreated.10 page(s

Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta-Analysis

Background: Anxiety disorders increase risk of future cardiovascular disease (CVD) and mortality, even after controlling for confounds including smoking, lifestyle, and socioeconomic status, and irrespective of a history of medical disorders. While impaired vagal function, indicated by reductions in heart rate variability (HRV), may be one mechanism linking anxiety disorders to CVD, prior studies have reported inconsistent findings highlighting the need for meta-analysis.Method: Studies comparing resting state HRV recordings in patients with an anxiety disorder as a primary diagnosis and healthy controls were considered for meta-analysis. Results: Meta-analyses were based on 36 articles, including 2086 patients with an anxiety disorder and 2294 controls. Overall, anxiety disorders were characterised by lower HRV (high frequency: Hedges’ g = -.29. 95%CI: -.41 to -.17, p < 0.001; time domain: Hedges’ g = -0.45, 95%CI: -0.57 to -0.33, p < .001) than controls. Panic Disorder (n=447), Post-Traumatic Stress Disorder (n=192), Generalized Anxiety Disorder (n=68), and Social anxiety disorder (n=90), but not Obsessive Compulsive Disorder (n=40), displayed reductions in high frequency HRV relative to controls (all ps < .001). Conclusions: Anxiety disorders are associated with reduced HRV, findings associated with a small to moderate effect size. Findings have important implications for future physical health and wellbeing of patients, highlighting a need for comprehensive cardiovascular risk reduction