Suicide attempts in clinical trials with paroxetine randomised against placebo

BACKGROUND: Inclusion of unpublished data on the effects of antidepressants on children has suggested unfavourable risk-benefit profiles for some of the drugs. Recent meta-analyses of studies on adults have indicated similar effects. We obtained unpublished data for paroxetine that have so far not been included in these analyses. METHODS: The documentation for drug registration contained 16 studies in which paroxetine had been randomised against placebo. We registered the number of suicides, suicide attempts and ideation. We corrected for duration of medication and placebo treatment and used a standard Bayesian statistical approach with varying priors. RESULTS: There were 7 suicide attempts in patients on the drug and 1 in a patient on placebo. We found that the probability of increased intensity of suicide attempts per year in adults taking paroxetine was 0.90 with a "pessimistic" prior, and somewhat less with two more neutral priors. CONCLUSION: Our findings support the results of recent meta-analyses. Patients and doctors should be warned that the increased suicidal activity observed in children and adolescents taking certain antidepressant drugs may also be present in adults

Cognitive vision system for control of dexterous prosthetic hands: Experimental evaluation

<p>Abstract</p> <p>Background</p> <p>Dexterous prosthetic hands that were developed recently, such as SmartHand and i-LIMB, are highly sophisticated; they have individually controllable fingers and the thumb that is able to abduct/adduct. This flexibility allows implementation of many different grasping strategies, but also requires new control algorithms that can exploit the many degrees of freedom available. The current study presents and tests the operation of a new control method for dexterous prosthetic hands.</p> <p>Methods</p> <p>The central component of the proposed method is an autonomous controller comprising a vision system with rule-based reasoning mounted on a dexterous hand (CyberHand). The controller, termed cognitive vision system (CVS), mimics biological control and generates commands for prehension. The CVS was integrated into a hierarchical control structure: 1) the user triggers the system and controls the orientation of the hand; 2) a high-level controller automatically selects the grasp type and size; and 3) an embedded hand controller implements the selected grasp using closed-loop position/force control. The operation of the control system was tested in 13 healthy subjects who used Cyberhand, attached to the forearm, to grasp and transport 18 objects placed at two different distances.</p> <p>Results</p> <p>The system correctly estimated grasp type and size (nine commands in total) in about 84% of the trials. In an additional 6% of the trials, the grasp type and/or size were different from the optimal ones, but they were still good enough for the grasp to be successful. If the control task was simplified by decreasing the number of possible commands, the classification accuracy increased (e.g., 93% for guessing the grasp type only).</p> <p>Conclusions</p> <p>The original outcome of this research is a novel controller empowered by vision and reasoning and capable of high-level analysis (i.e., determining object properties) and autonomous decision making (i.e., selecting the grasp type and size). The automatic control eases the burden from the user and, as a result, the user can concentrate on what he/she does, not on how he/she should do it. The tests showed that the performance of the controller was satisfactory and that the users were able to operate the system with minimal prior training.</p

Additive QTLs on three chromosomes control flowering time in woodland strawberry (Fragaria vesca L.)

Flowering time is an important trait that affects survival, reproduction and yield in both wild and cultivated plants. Therefore, many studies have focused on the identification of flowering time quantitative trait locus (QTLs) in different crops, and molecular control of this trait has been extensively investigated in model species. Here we report the mapping of QTLs for flowering time and vegetative traits in a large woodland strawberry mapping population that was phenotyped both under field conditions and in a greenhouse after flower induction in the field. The greenhouse experiment revealed additive QTLs in three linkage groups (LG), two on both LG4 and LG7, and one on LG6 that explain about half of the flowering time variance in the population. Three of the QTLs were newly identified in this study, and one co-localized with the previously characterized FvTFL1 gene. An additional strong QTL corresponding to previously mapped PFRU was detected in both field and greenhouse experiments indicating that gene(s) in this locus can control the timing of flowering in different environments in addition to the duration of flowering and axillary bud differentiation to runners and branch crowns. Several putative flowering time genes were identified in these QTL regions that await functional validation. Our results indicate that a few major QTLs may control flowering time and axillary bud differentiation in strawberries. We suggest that the identification of causal genes in the diploid strawberry may enable fine tuning of flowering time and vegetative growth in the closely related octoploid cultivated strawberry.Peer reviewe

Epidemiology characteristics, methodological assessment and reporting of statistical analysis of network meta-analyses in the field of cancer

Because of the methodological complexity of network meta-analyses (NMAs), NMAs may be more vulnerable to methodological risks than conventional pair-wise meta-analysis. Our study aims to investigate epidemiology characteristics, conduction of literature search, methodological quality and reporting of statistical analysis process in the field of cancer based on PRISMA extension statement and modified AMSTAR checklist. We identified and included 102 NMAs in the field of cancer. 61 NMAs were conducted using a Bayesian framework. Of them, more than half of NMAs did not report assessment of convergence (60.66%). Inconsistency was assessed in 27.87% of NMAs. Assessment of heterogeneity in traditional meta-analyses was more common (42.62%) than in NMAs (6.56%). Most of NMAs did not report assessment of similarity (86.89%) and did not used GRADE tool to assess quality of evidence (95.08%). 43 NMAs were adjusted indirect comparisons, the methods used were described in 53.49% NMAs. Only 4.65% NMAs described the details of handling of multi group trials and 6.98% described the methods of similarity assessment. The median total AMSTAR-score was 8.00 (IQR: 6.00-8.25). Methodological quality and reporting of statistical analysis did not substantially differ by selected general characteristics. Overall, the quality of NMAs in the field of cancer was generally acceptable

Backward walking training improves balance in school-aged boys

<p>Abstract</p> <p>Background</p> <p>Falls remain a major cause of childhood morbidity and mortality. It is suggested that backward walking (BW) may offer some benefits especially in balance and motor control ability beyond those experienced through forward walking (FW), and may be a potential intervention for prevention of falls. The objective of this study was to investigate the effects of BW on balance in boys.</p> <p>Methods</p> <p>Sixteen healthy boys (age: 7.19 ± 0.40 y) were randomly assigned to either an experimental or a control group. The experimental group participated in a BW training program (12-week, 2 times weekly, and 25-min each time) but not the control group. Both groups had five dynamic balance assessments with a Biodex Stability System (anterior/posterior, medial/lateral, and overall balance index) before, during and after the training (week- 0, 4, 8, 12, 24). Six control and six experimental boys participated in a study comparing kinematics of lower limbs between FW and BW after the training (week-12).</p> <p>Results</p> <p>The balance of experimental group was better than that of control group after 8 weeks of training (<it>P </it>< 0.01), and was still better than that of control group (<it>P </it>< 0.05), when the BW training program had finished for 12 weeks. The kinematic analysis indicated that there was no difference between control and experimental groups in the kinematics of both FW and BW gaits after the BW training (<it>P </it>> 0.05). Compared to FW, the duration of stance phase of BW tended to be longer, while the swing phase, stride length, walking speed, and moving ranges of the thigh, calf and foot of BW decreased (<it>P </it>< 0.01).</p> <p>Conclusion</p> <p>Backward walking training in school-aged boys can improve balance.</p

Treatment of psychotic symptoms in bipolar disorder with aripiprazole monotherapy: A meta-analysis

Background: We present a systematic review and meta-analysis of the available clinical trials concerning the usefulness of aripiprazole in the treatment of the psychotic symptoms in bipolar disorder.Methods: A systematic MEDLINE and repository search concerning clinical trials for aripiprazole in bipolar disorder was conducted.Results: The meta-analysis of four randomised controlled trials (RCTs) on acute mania suggests that the effect size of aripiprazole versus placebo was equal to 0.14 but a more reliable and accurate estimation is 0.18 for the total Positive and Negative Syndrome Scale (PANSS) score. The effect was higher for the PANSS-positive subscale (0.28), PANSS-hostility subscale (0.24) and PANSS-cognitive subscale (0.20), and lower for the PANSS-negative subscale (0.12). No data on the depressive phase of bipolar illness exist, while there are some data in favour of aripiprazole concerning the maintenance phase, where at week 26 all except the total PANSS score showed a significant superiority of aripiprazole over placebo (d = 0.28 for positive, d = 0.38 for the cognitive and d = 0.71 for the hostility subscales) and at week 100 the results were similar (d = 0.42, 0.63 and 0.48, respectively).Conclusion: The data analysed for the current study support the usefulness of aripiprazole against psychotic symptoms during the acute manic and maintenance phases of bipolar illness. © 2009 Fountoulakis et al; licensee BioMed Central Ltd

Treatment and outcomes of an Australian cohort of outpatients with bipolar 1 or schizoaffective disorder over twenty-four months : implications for clinical practice

Background The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with &lsquo;real-world&rsquo; treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.Methods Participants prescribed either conventional mood stabilizers (CMS; n&thinsp;=&thinsp;155) alone, or olanzapine with, or without, CMS (olanzapine&thinsp;&plusmn;&thinsp;CMS; n&thinsp;=&thinsp;84) were assessed every 3&thinsp;months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale &ndash; Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.Results On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24&thinsp;months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine&thinsp;&plusmn;&thinsp;CMS (61%;) cohorts.Conclusions Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.<br /

The Effects of Cognitive Therapy versus ‘No Intervention’ for Major Depressive Disorder

BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. METHODS/PRINCIPAL FINDINGS: We used The Cochrane systematic review methodology with meta-analyses and trial sequential analyses of randomized trials comparing the effects of cognitive therapy versus 'no intervention' for major depressive disorder. Participants had to be older than 17 years with a primary diagnosis of major depressive disorder to be eligible. Altogether, we included 12 trials randomizing a total of 669 participants. All 12 trials had high risk of bias. Meta-analysis on the Hamilton Rating Scale for Depression showed that cognitive therapy significantly reduced depressive symptoms (four trials; mean difference -3.05 (95% confidence interval (Cl), -5.23 to -0.87; P<0.006)) compared with 'no intervention'. Trial sequential analysis could not confirm this result. Meta-analysis on the Beck Depression Inventory showed that cognitive therapy significantly reduced depressive symptoms (eight trials; mean difference on -4.86 (95% CI -6.44 to -3.28; P = 0.00001)). Trial sequential analysis on these data confirmed the result. Only a few trials reported on 'no remission', suicide inclination, suicide attempts, suicides, and adverse events without significant differences between the compared intervention groups. DISCUSSION: Cognitive therapy might be an effective treatment for depression measured on Hamilton Rating Scale for Depression and Beck Depression Inventory, but these outcomes may be overestimated due to risks of systematic errors (bias) and random errors (play of chance). Furthermore, the effects of cognitive therapy on no remission, suicidality, adverse events, and quality of life are unclear. There is a need for randomized trials with low risk of bias, low risk of random errors, and longer follow-up assessing both benefits and harms with clinically relevant outcome measures