Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study.

The negative symptoms of schizophrenia remain a major clinical challenge. Mirtazapine is an antidepressant with antagonist properties at 5-HT2A, 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects. Many of these pharmacological actions have clinical or preclinical evidence of efficacy in schizophrenia. This study was a 6-week randomized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The primary finding of the trial was a 42% reduction in Positive and Negative Syndrome Scale (PANSS) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks (mirtazapine 13.9, SD 1.56; placebo 23.9, SD 1.56; P = 0.000, F = 20.31, d.f. = 1). The PANNS total scores, Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo. There was no difference between the groups on the Hamilton depression scale at endpoint, suggesting that the improvement in negative symptoms was not an artifact of mood improvement. These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia.

Efficacy of nefazodone in the treatment of neuroleptic induced extrapyramidal side effects: a double-blind randomised parallel group placebo-controlled trial.

Many atypical antipsychotics show antagonism at both serotonergic and dopaminergic neurones and show fewer extrapyramidal side effects (EPS). Nefazodone blocks postsynaptic 5HT2A receptors and weakly inhibits serotonin reuptake. This study aimed to elucidate the role of nefazodone in the treatment of antipsychotic-induced EPS. The trial was a double-blind, randomised, placebo-controlled trial of patients requiring antipsychotic treatment with haloperidol 10mg daily; from which a subgroup of patients who developed EPS were selected for the study. Patients were randomised to add-on therapy with either placebo (n=24) or nefazodone (n=25) 100mg bd. EPS were measured on days 0, 3 and 7 using the Simpson Angus, Barnes akathisia, abnormal involuntary movement and Chouinard scales. Nefazodone significantly reduced EPS as measured by both the Simpson Angus scale and CGI (p=0.007 and 0.0247, respectively). Akathisia and tardive dyskinesia did not differ between the two groups (p=0.601; p=0.507, respectively). These results suggest the role of 5HT2 antagonism in the mechanism of action of atypical antipsychotics with respect to lowering rates of drug-induced EPS. In addition, a therapeutic role for nefazodone is suggested in the treatment of antipsychotic-induced EPS.

Lamotrigine and the treatment of mania in bipolar disorder

Anticonvulsants, including valproate and carbamazepine, have established efficacy in the treatment of mania. The anticonvulsant, lamotrigine. has been reported to have antimanic and antidepressant efficacy, and mood-stabilising effects in case reports and preliminary open trials. The efficacy and tolerability of lamotrigine has been compared with olanzapine and lithium in a randomised, prospective, controlled fashion over a period of 4 weeks treatment in a total of 45 hospitalised patients with DSM-IV-defined mania. Significant improvements of a similar magnitude were observed for all treatment groups and lamotrigine was well tolerated. Mechanisms of action proposed to explain the antimanic activity of lamotrigine include inhibition of voltage-sensitive and use-dependent sodium channels, inhibition of glutamate release and calcium channel blockade. Platelet studies have indicated supersensitivity of glutamate receptors and increased intracellular calcium concentrations in patients with mania. Further clinical and mechanistic studies of lamotrigine use in mania are warranted.

Reboxetine add on therapy to haloperidol in the treatment of schizophrenia: a preliminary double-blind randomized placebo-controlled study.

The negative symptoms of schizophrenia remain a major clinical challenge. Reboxetine is an antidepressant whose major mechanism of action is as a noradrenergic reuptake inhibitor. This study was a 6-week randomized placebo-controlled trial of reboxetine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia. The trial failed to demonstrate any significant difference between the placebo and reboxetine groups on any of the outcome measures. This trial does not suggest that increased noradreneregic drive mediated by reuptake inhibition in patients taking dopamine antagonists is of therapeutic value in schizophrenia.

Fluoxetine treatment of acral lick dermatitis in dogs: a placebo-controlled randomized double blind trial.

The aim of the study was to assess the efficacy and tolerability of fluoxetine treatment of acral lick dermatitis (ALD) in dogs and to investigate ALD as an animal model of obsessive-compulsive disorder (OCD). Sixty-three dogs with ALD were treated with fluoxetine 20 mg daily, or placebo, for 6 weeks. In the fluoxetine group, owners rated both appearance of the lesion (t = 10.2, df = 29, P < 0.0001) and licking behavior (t = 10.2, df = 29, P < 0.0001) as significantly improved by the end of the trial. Veterinarian-rated pre- and post-treatment photographs showed statistically significant improvement in the fluoxetine group (mean = 2.55). There were no significant changes in the placebo group as rated by owners and veterinarians. These results demonstrate the efficacy of fluoxetine in the treatment of ALD and lend further support to ALD as an animal model of OCD.

Comparison between nanofiltration and forward osmosis in the treatment of dye solutions

Colour removal and the flux behaviour of nanofiltration (NF-DOW FILMTEC-NF245) and forward osmosis (FO-a flat sheet cellulose triacetate membrane with a woven embedded backing support) membranes were investigated in this study. The NF membrane was employed to perform dye removal experiments with aqueous solutions containing 15 g/L of NaCl and different concentrations of Acid Green 25, Remazol Brilliant Orange FR and Remazol Blue BR dyes. The increase in dye concentration resulted in a decline in water permeability and an increase in colour removal. When the concentrations of dye solutions varied from 250 to 1000 mg/L, at 0.8 bar of trans-membrane pressure, the NF system exhibited a steady permeate flux of more 30 L/m2h and a colour removal of more than 99%; salt rejection was more than 20.0%. Furthermore, the FO system possessed high dye rejection efficiency (almost 100%), with low permeate flux of around 2.0 L/m2h, when using dye solutions as feed streams and seawater as draw stream. The mode of operation (either FO or pressure retarded osmosis (PRO) did not change the flux significantly but PRO mode always produced higher fluxes than FO mode under the operating conditions used in this study. While both NF and FO can be used to reduce the volume of effluent containing dyes from textile industries, the energy spent in NF on applied pressure can be substituted by the osmotic pressure of draw solution in FO when concentrated draw solutions such as sea water or reverse osmosis concentrate are readily available.

N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review

Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area.

Interobserver Variability in the Treatment of Little Finger Metacarpal Neck Fractures

Purpose To address the null hypothesis that surgeons shown radiographs of little finger metacarpal neck fractures with measured fracture angulation would recommend surgery as often as surgeons shown unmarked radiographs. Methods Members of the Science of Variation Group, an international collaboration of fully trained orthopedic and trauma surgeons, were asked to review 20 little finger metacarpal neck fracture cases, which included a vignette and 3 high-quality radiographs. Members were then randomized to review radiographs with or without measured fracture angulation on the lateral view and select operative or nonoperative management. Results Surgeons shown radiographs with measured angulation were more likely to recommend surgery, and there was less variability among these surgeons, particularly for fractures with less angular deformity. Conclusions Measured fracture angulation has a small but significant influence on treatment recommendations for little finger metacarpal neck fractures.

Treatment of type 2 diabetes with antioxidant vitamin C therapy

High dose vitamin C supplementation significantly improved insulin sensitivity in skeletal muscle of people with type 2 diabetes. This clinically relevant improvement corresponded with improvements in vitamin C and oxidative stress levels in skeletal muscle. Vitamin C supplementation could be an effective adjunct therapy in people with type 2 diabetes.

Electrochemical treatment of AA5083 aluminium alloy in ionic liquids

 Dr Huang was one of the first people to explore the possibility of reducing corrosion on aluminium alloys by electrochemical treatments in ionic liquids. Her study showed that the corrosion rates of aluminium alloys were indeed reduced after various electrochemical treatments in the target ionic liquids.

Aptamer-targeted oligonucleotide theranostics: a smarter approach for brain delivery and the treatment of neurological diseases

Aptamers represent the novel class of oligonucleotides holding multiple applications in the area of biomedicine. The advancements introduced with the Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach further eased the scope of producing modified aptamers within a short span yet retaining the properties of stability and applicability. In the recent times, aptamers were identified to have the potential for penetrating into the deep human crevices and thus can be utilized in addressing the issues of complex neurological disorders. Considering the specificity and stability enhancement by chemical modifications, aptamer-based nanotechnologies may have great potential for future therapeutics and diagnostics (theranostics). The research community has already witnessed success with the approval of macugen (an anti-vascular endothelial growth factor aptamer) for treating degenerating eye disease, and hopefully those that are in the clinical trials will soon be translated for human application. Herein, we have summarized the aptamer chemistry, aptamer-nanoconjugates and their applications against neurological diseases.

Nocebo effects in the treatment of major depression: results from an individual study participant-level meta-analysis of the placebo arm of duloxetine clinical trials

BACKGROUND: The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. METHOD: This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. RESULTS: TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. DISCUSSION: In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. CONCLUSIONS: The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.