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Molecular Psychiatry Oct 2015Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been proposed to have an important role in the cognitive impairments observed in schizophrenia. Although... (Meta-Analysis)
Meta-Analysis Review
Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been proposed to have an important role in the cognitive impairments observed in schizophrenia. Although glutamate modulators may be effective in reversing such difficult-to-treat conditions, the results of individual studies thus far have been inconsistent. We conducted a systematic review and meta-analysis to examine whether glutamate positive modulators have beneficial effects on cognitive functions in patients with schizophrenia. A literature search was conducted to identify double-blind randomized placebo-controlled trials in schizophrenia or related disorders, using Embase, Medline, and PsycINFO (last search: February 2015). The effects of glutamate positive modulators on cognitive deficits were evaluated for overall cognitive function and eight cognitive domains by calculating standardized mean differences (SMDs) between active drugs and placebo added to antipsychotics. Seventeen studies (N=1391) were included. Glutamate positive modulators were not superior to placebo in terms of overall cognitive function (SMD=0.08, 95% confidence interval=-0.06 to 0.23) (11 studies, n=858) nor each of eight cognitive domains (SMDs=-0.03 to 0.11) (n=367-940) in this population. Subgroup analyses by diagnosis (schizophrenia only studies), concomitant antipsychotics, or pathway of drugs to enhance the glutamatergic neurotransmission (glycine allosteric site of NMDA receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) suggested no procognitive effect of glutamate positive modulators. Further, no effect was found in individual compounds on cognition. In conclusion, glutamate positive modulators may not be effective in reversing overall cognitive impairments in patients with schizophrenia as adjunctive therapies.
Topics: Cognition Disorders; Double-Blind Method; Excitatory Amino Acid Agents; Humans; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Schizophrenic Psychology; Synaptic Transmission
PubMed: 26077694
DOI: 10.1038/mp.2015.68 -
The Cochrane Database of Systematic... Oct 2014In myasthenia gravis, antibody-mediated blockade of acetylcholine receptors at the neuromuscular junction abolishes the naturally occurring 'safety factor' of synaptic... (Review)
Review
BACKGROUND
In myasthenia gravis, antibody-mediated blockade of acetylcholine receptors at the neuromuscular junction abolishes the naturally occurring 'safety factor' of synaptic transmission. Acetylcholinesterase inhibitors provide temporary symptomatic treatment of muscle weakness but there is controversy about their long-term efficacy, dosage and side effects. This is the second update of a review published in The Cochrane Library Issue 2, 2011.
OBJECTIVES
To evaluate the efficacy of acetylcholinesterase inhibitors in all forms of myasthenia gravis.
SEARCH METHODS
On 8 July 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE for randomised controlled trials and quasi-randomised controlled trials regarding usage of acetylcholinesterase inhibitors in myasthenia gravis. Two authors scanned the articles for any study eligible for inclusion. We also contacted the authors and known experts in the field to identify additional published or unpublished data and searched clinical trials registries for ongoing trials.
SELECTION CRITERIA
The types of studies were randomised or quasi-randomised trials. Participants were myasthenia gravis patients diagnosed by an internationally accepted definition. The intervention was treatment with any form of acetylcholinesterase inhibitor. Types of outcome measures Primary outcome measureImprovement in the presenting symptoms within one to 14 days of the start of treatment. Secondary outcome measures(1) Improvement in the presenting symptoms more than 14 days after the start of treatment.(2) Change in impairment measured by a recognised and preferably validated scale, such as the quantitative myasthenia gravis score, within one to 14 days and more than 14 days after the start of treatment.(3) Myasthenia Gravis Association of America post-intervention status more than 14 days after start of treatment.(4) Adverse events including muscarinic side effects.
DATA COLLECTION AND ANALYSIS
One author (MMM) extracted the data, which were checked by a second author. We contacted study authors for extra information and collected data on adverse effects from the trials.
MAIN RESULTS
We did not find any large randomised or quasi-randomised trials of acetylcholinesterase inhibitors in generalised myasthenia gravis either for the first version of this review or this update. One cross-over randomised trial using intranasal neostigmine in a total of 10 participants was only available as an abstract. It included three participants with ocular myasthenia gravis and seven with generalised myasthenia gravis. Symptoms of myasthenia gravis (measured as improvement in at least one muscle function) improved in nine of the 10 participants after the two-week neostigmine treatment phase. No participant improved after the placebo phase. Lack of detail in the report meant that the risk of bias was unclear. Adverse events were minor.
AUTHORS' CONCLUSIONS
Except for one small and inconclusive trial of intranasal neostigmine, no other randomised controlled trials have been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. The response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in a placebo arm of treatment would be difficult to justify.
Topics: Administration, Intranasal; Cholinesterase Inhibitors; Humans; Myasthenia Gravis; Neostigmine; Randomized Controlled Trials as Topic
PubMed: 25310725
DOI: 10.1002/14651858.CD006986.pub3 -
Schizophrenia Bulletin Jan 2015Cognitive deficits are commonly observed in patients with schizophrenia. Converging lines of evidence suggest that these deficits are associated with impaired long-term... (Review)
Review
Cognitive deficits are commonly observed in patients with schizophrenia. Converging lines of evidence suggest that these deficits are associated with impaired long-term potentiation (LTP). In our systematic review, this hypothesis is evaluated using neuroimaging literature focused on proton magnetic resonance spectroscopy, positron emission tomography, and single-photon emission computed tomography. The review provides evidence for abnormal dopaminergic, GABAergic, and glutamatergic neurotransmission in antipsychotic-naive/free patients with schizophrenia compared with healthy controls. The review concludes with a model illustrating how these abnormalities could lead to impaired LTP in patients with schizophrenia and consequently cognitive deficits.
Topics: Brain; Cognition Disorders; Dopamine; Glutamic Acid; Humans; Long-Term Potentiation; Magnetic Resonance Spectroscopy; Positron-Emission Tomography; Schizophrenia; Schizophrenic Psychology; Synaptic Transmission; Tomography, Emission-Computed, Single-Photon; gamma-Aminobutyric Acid
PubMed: 25249654
DOI: 10.1093/schbul/sbu132 -
Sensors (Basel, Switzerland) Jul 2014The evoked electromyographic signal (eEMG) potential is the standard index used to monitor both electrical changes within the motor unit during muscular activity and the... (Review)
Review
The evoked electromyographic signal (eEMG) potential is the standard index used to monitor both electrical changes within the motor unit during muscular activity and the electrical patterns during evoked contraction. However, technical and physiological limitations often preclude the acquisition and analysis of the signal especially during functional electrical stimulation (FES)-evoked contractions. Hence, an accurate quantification of the relationship between the eEMG potential and FES-evoked muscle response remains elusive and continues to attract the attention of researchers due to its potential application in the fields of biomechanics, muscle physiology, and rehabilitation science. We conducted a systematic review to examine the effectiveness of eEMG potentials to assess muscle force and fatigue, particularly as a biofeedback descriptor of FES-evoked contractions in individuals with spinal cord injury. At the outset, 2867 citations were identified and, finally, fifty-nine trials met the inclusion criteria. Four hypotheses were proposed and evaluated to inform this review. The results showed that eEMG is effective at quantifying muscle force and fatigue during isometric contraction, but may not be effective during dynamic contractions including cycling and stepping. Positive correlation of up to r = 0.90 (p < 0.05) between the decline in the peak-to-peak amplitude of the eEMG and the decline in the force output during fatiguing isometric contractions has been reported. In the available prediction models, the performance index of the eEMG signal to estimate the generated muscle force ranged from 3.8% to 34% for 18 s to 70 s ahead of the actual muscle force generation. The strength and inherent limitations of the eEMG signal to assess muscle force and fatigue were evident from our findings with implications in clinical management of spinal cord injury (SCI) population.
Topics: Electromyography; Evidence-Based Medicine; Humans; Muscle Contraction; Muscle Fatigue; Muscle Strength; Muscle, Skeletal; Neuromuscular Junction; Spinal Cord Injuries; Spinal Cord Stimulation; Synaptic Transmission
PubMed: 25025551
DOI: 10.3390/s140712598