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Background: Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive deficits. Furthermore, studies in nonhuman primates (NHP) have suggested that intermittent administration of low doses of D1R agonists produce long-lasting reversals in cognitive deficits. The purpose of this trial was to test whether a similar design, involving subacute intermittent administration of low doses of a full, selective agonist at D1Rs, DAR-0100A, would improve cognitive deficits in SCZ.Methods: We randomized 49 clinically stable individuals with SCZ to three weeks of intermittent treatment with 0.5 mg or 15 mg of DAR-0100A, or placebo (normal saline). Functional magnetic resonance imaging (fMRI) BOLD was used to evaluate the effects of drug administration on brain activity during a working memory (WM) task. Effects on cognition were also assessed using the MATRICS and the N-back task as primary endpoints. The CogState battery was used as a secondary endpoint.Results: There were no observed treatment effects on either the BOLD fMRI signal during WM tasks or the WM domains of the MATRICS. Moderate improvement was detected on the CogState battery and on the attention domain of the MATRICS.Conclusion: These results suggest that low doses of D1 agonists that do not result in measureable occupancy of the D1R do not reliably improve cognition in SCZ, unlike the observations in NHP. As this drug is limited by its pharmacokinetic profile, better D1R agonists that can achieve adequate levels of D1R occupancy are needed to test the efficacy of this mechanism for cognitive enhancement in SCZ. [ABSTRACT FROM AUTHOR]

Biological mediators have been used to enhance periodontal regeneration. The aim of this prospective randomized controlled study was to evaluate the safety and effectiveness of 3 doses of fibroblast growth factor 2 (FGF-2) when combined with a β-tricalcium phosphate (β-TCP) scaffold carrier placed in vertical infrabony periodontal defects in adult patients. In this double-blinded, dose-verification, externally monitored clinical study, 88 patients who required surgical intervention to treat a qualifying infrabony periodontal defect were randomized to 1 of 4 treatment groups-β-TCP alone (control) and 0.1% recombinant human FGF-2 (rh-FGF-2), 0.3% rh-FGF-2, and 0.4% rh-FGF-2 with β-TCP-following scaling and root planing of the tooth prior to a surgical appointment. Flap surgery was performed with EDTA conditioning of the root prior to device implantation. There were no statistically significant differences in patient demographics and baseline characteristics among the 4 treatment groups. When a composite outcome of gain in clinical attachment of 1.5 mm was used with a linear bone growth of 2.5 mm, a dose response pattern detected a plateau in the 0.3% and 0.4% rh-FGF-2/β-TCP groups with significant improvements over control and 0.1% rh-FGF-2/β-TCP groups. The success rate at 6 mo was 71% in the 2 higher-concentration groups, as compared with 45% in the control and lowest treatment groups. Percentage bone fill in the 2 higher-concentration groups was 75% and 71%, compared with 63% and 61% in the control and lowest treatment group. No increases in specific antibody to rh-FGF-2 were detected, and no serious adverse events related to the products were reported. The results from this multicenter trial demonstrated that the treatment of infrabony vertical periodontal defects can be enhanced with the addition of rh-FGF-2/β-TCP (ClinicalTrials.gov NCT01728844). [ABSTRACT FROM AUTHOR]

The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children. In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4–12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. The difference between the two groups in the frequency of side effects was not significant. In conclusion, galantamine augmentation was shown to be a relatively effective and safe augmentative strategy for alleviating some of the autism-related symptoms. [ABSTRACT FROM PUBLISHER]

The article discusses a study conducted to examine the safety and efficacy of onabotulinumtoxinA (Botox) for plantarflexor overactivity following stroke. It highlights that Botulinum toxin type A (BoNT-A) is treatment of choice to reduce the neurogenic component of focal hypertonia; and leads to muscle overactivity causing equinovarus ankle deformity after stroke. The result suggests that its injection for ankle flexor overactivity after stroke was safe but did not alter local spasticity.

Objective: To test the efficacy of calcium dobesilate (CaD) in chronic venous insufficiency (CVI). Method: Double-blind, parallel groups, placebo-controlled, multicentre trial in adult patients with symptomatic CVI and pitting oedema. Wearing of compression stockings Class II was admitted. During treatment period of eight weeks, the patients received CaD 3 x 500 mg/day or placebo. The leg volume calculation was based on a truncated cone model. Results: A total of 256 patients was randomized to treatment (dobesilate: n = 132, placebo: n = 124); the demographic and anamnestic data at admission were comparable in the two therapeutic groups. The volume of the lower calf diminished in the dobesilate group at the end of the active treatment period by -64.72 ± 111.93 cm³ (mean ± SD), independent of the concomitant usage of compression stockings versus placebo +0.8 ± 152.98 cm³ (P = 0.0002). The symptoms of pain, discomfort, heavy legs, tired legs, tingling, itching and cramps, as well as the global assessments by investigators and patients, also improved significantly (P < 0.05) better in the dobesilate group at the end of the treatment. The observed adverse events correspond to the known profile. Conclusion: Dobesilate reduces leg oedema and improves the symptoms of objectively diagnosed CVI, independent of the concomitant usage of compression stockings. [ABSTRACT FROM AUTHOR]

Most people with episodic tension-type headache (TTH) treat themselves with over-the-counter analgesics. In the absence of clear evidence of dose-related efficacy of the two most commonly used analgesics, aspirin (acetylsalicylic acid) and paracetamol (acetaminophen), this study compared two doses of each with placebo. In a double-blind, double-dummy, randomized parallel-groups comparative trial, 638 consenting subjects aged 16-65 years with episodic TTH (but not migraine) by IHS criteria were recruited from the UK general population by advertisement. They treated one episode of moderate or severe TTH with a single dose of 500 or 1000 mg aspirin, 500 or 1000 mg paracetamol or placebo. The primary objective was to compare aspirin 1000 mg with placebo, and the primary end-point was subjective pain relief (total or worthwhile) 2 h after treatment ('response'). Additionally, pain intensity on a 100-mm visual analogue scale and functional impairment were monitored regularly for 4 h and at 24 h, although rescue medication was allowed after 2 h. The analysis was of the intention-to-treat population of 542 who took treatment (all providing outcome data). Treatment groups were matched at baseline. Aspirin 1000 mg (75.7% response rate; P = 0.0009) and to a lesser extent aspirin 500 mg (70.3%; P = 0.011) and paracetamol 1000 mg (71.2%; P = 0.007), but not paracetamol 500 mg (63.8%; P = 0.104), were statistically more effective than placebo despite a high placebo-response rate (54.5%). Outcome was not affected by headache intensity at baseline. Secondary end-points including functional recovery (by median times of 4.0-13.5 h) were consistent with these findings, although a minority of subjects recorded long-duration functional impairment (37-54 h). Adverse events reported by 13.4-18.9% of subjects were mild or moderate, and transient. No safety concerns arose. [ABSTRACT FROM AUTHOR]

S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placebo-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F = 4.93; p = 0.033) and month 4 (F = 4.55; p = 0.041). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should be interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study. [ABSTRACT FROM AUTHOR]

Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n = 46) and 1.4 mg (n = 39). Efficacy, tolerability and safety of each dose were compared with those of placebo (n = 41). At 2 h after injection, headache was absent or mild in 83% and 82% of patients receiving alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p < or = 0.002). Complete relief from headache was achieved in 72% (1.4 mg). Time to onset of relief decreased with increasing alniditan dose, and there was a dose-dependent reduction in headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and headache recurred within 24 h in only 16% of the patients who initially responded to alniditan 1.4 mg, significantly less than for placebo (p = 0.018). Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that alniditan 1.4 mg sc may have advantages over sumatriptan 6 mg sc in providing complete relief from acute migraine headache, and may be associated with fewer headache recurrences within 24 h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine. [ABSTRACT FROM AUTHOR]