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The Cochrane Database of Systematic... Mar 2018Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering.
OBJECTIVES
To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use.
SEARCH METHODS
We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions.
AUTHORS' CONCLUSIONS
Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.
Topics: Adult; Antidepressive Agents; Aspartic Acid; Benzodiazepines; Buspirone; Carbamazepine; Ethylamines; Flumazenil; Homeopathy; Humans; Imidazoles; Lithium Compounds; Melatonin; Paroxetine; Pregabalin; Progesterone; Pyridines; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Sulfides; Withholding Treatment
PubMed: 29543325
DOI: 10.1002/14651858.CD011481.pub2 -
Medicine Nov 2018Association between the D-repeat of asporin (ASPN) gene and osteoarthritis (OA) was still inconsistent. We performed this meta-analysis to systematically assess the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Association between the D-repeat of asporin (ASPN) gene and osteoarthritis (OA) was still inconsistent. We performed this meta-analysis to systematically assess the D-repeat polymorphisms in OA susceptibility.
METHODS
Relevant studies were enrolled by searching databases. Odd ratios (ORs) with 95% confidence intervals (95% CIs) were used for evaluating the association between ASPN gene and OA. Heterogeneity was calculated using the Q statistic, and three different subgroup analyses were performed on ethnicity, gender, and OA positions respectively. False discovery rate (FDR) was applied to regulate the multiple comparisons.
RESULTS
Twelve qualified articles involving 5190 OA patients and 5167 healthy controls were included. With D13 polymorphism, Caucasian male patients have low OA susceptibility (P = .008, PFDR = .024, OR [95% CI] = 0.83 [0.73-0.95]). As to D14 polymorphism, all male patients (P = .0004, PFDR = .001, OR [95% CI] = 1.38 [1.15-1.64]), Asian male patients (P = .01, PFDR = .01, OR [95% CI] = 1.72 [1.11-2.66]), and Caucasian male patients (P = .005, PFDR = .001, OR [95% CI] = 1.32 [1.09-1.60]) have high OA susceptibility. In the pooled-population of KOA with D14 polymorphism, overall male patients (P = .03, PFDR = .045, OR [95% CI] = 1.35 [1.02-1.78]) and Asian male patients (P = .01, PFDR = .03, OR [95% CI] = 1.72 [1.11-2.66]) have high OA risk. With D16 polymorphism, Latin America patients may have high OA risk (P = .04, PFDR = .15, OR [95% CI] = 1.43 [1.02-2.01]).
CONCLUSION
Our results suggest that D-repeat of ASPN gene is mainly associated with male patients. The D13 polymorphism plays a protective role for OA in Caucasians male individuals while D14 plays a risk factor for KOA in male patients.
Topics: D-Aspartic Acid; Ethnicity; Extracellular Matrix Proteins; Female; Genetic Predisposition to Disease; Humans; Male; Osteoarthritis; Polymorphism, Genetic
PubMed: 30407347
DOI: 10.1097/MD.0000000000013163 -
International Journal of Reproductive... Jan 2017D-Aspartic acid (D-Asp) is in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions. Recently, it has been reported... (Review)
Review
BACKGROUND
D-Aspartic acid (D-Asp) is in invertebrate and vertebrate neuroendocrine tissues, where it carries out important physiological functions. Recently, it has been reported that D-Asp is involved in the synthesis and release of testosterone and is assumed can be used as a testosterone booster for infertile men, and by athletes to increase muscle mass and strength.
OBJECTIVE
The aim of this review is to summarize available evidence related to the effects of D-Asp on serum testosterone levels.
MATERIALS AND METHODS
We conducted a systematic review of all type studies, which evaluated the effect of the D-Asp on blood testosterone including published papers until October 2015, using PubMed, ISI Web of Science, ProQuest and Scopus database.
RESULTS
With 396 retrieved records, 23 animal studies and 4 human studies were included. In vivo and in vitro animal studies revealed the effect of D-Asp depending on species, sex and organ-specific. Our results showed that exogenous D-Asp enhances testosterone levels in male animal's studies, whereas studies in human yielded inconsistent results. The evidence for this association in man is still sparse, mostly because of limited number and poor quality studies.
CONCLUSION
There is an urgent need for more and well-designed human clinical trials with larger sample sizes and longer duration to investigate putative effects of D-Asp on testosterone concentrations.
PubMed: 28280794
DOI: No ID Found -
Acta Orthopaedica Et Traumatologica... Oct 2017Studies have assessed the association between aspartic acid (D)-repeat polymorphism in the gene encoding Asporin (ASPN) and knee osteoarthritis (KOA) risk, but the... (Review)
Review
OBJECTIVE
Studies have assessed the association between aspartic acid (D)-repeat polymorphism in the gene encoding Asporin (ASPN) and knee osteoarthritis (KOA) risk, but the results were inconclusive and contradictory. Therefore, we performed a meta-analysis to investigate the association between ASPN gene D-repeat polymorphism and KOA risk.
METHODS
Eligible studies were identified by searching several electronic databases for relevant reports published before September 2016. The pooled odds ratios (ORs) for the association between ASPN polymorphism and KOA and their corresponding 95% confidence intervals (CIs) were estimated using the random- or fixed-effect model.
RESULTS
A total of eleven case-control studies in ten publications with 4610 KOA cases and 3621 controls were included for the ASPN D-repeat polymorphism. Overall, no significant association was detected for D14 allele carrier (D14 vs. D13: OR = 1.10, 95% CI = 0.90-1.36, p = 0.32). Meta-analysis of D14 vs. other alleles and D13 vs. other alleles showed the same pattern of KOA association as the D14 vs. D13 (OR = 1.30, 95% CI = 1.00-1.70, p = 0.06; OR = 0.93, 95% CI = 0.82-1.06, p = 0.33, respectively). Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of KOA was found in the European and Asians populations (OR = 1.05, 95% CI = 0.91-1.21, p = 0.49; OR = 0.98, 95% CI = 0.78-1.23, p = 0.88, respectively).
CONCLUSIONS
The present meta-analysis suggests that the ASPN D-repeat polymorphism is not associated with an increased KOA risk. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings.
LEVEL OF EVIDENCE
Level III diagnostic study.
Topics: D-Aspartic Acid; Extracellular Matrix Proteins; Humans; Osteoarthritis, Knee; Polymorphism, Genetic
PubMed: 28889984
DOI: 10.1016/j.aott.2017.08.001 -
Nutrients Aug 2020Aberrant fetal growth remains a leading cause of perinatal morbidity and mortality and is associated with a risk of developing non-communicable diseases later in life....
Aberrant fetal growth remains a leading cause of perinatal morbidity and mortality and is associated with a risk of developing non-communicable diseases later in life. We performed a systematic review and meta-analysis combining human and animal studies to assess whether prenatal amino acid (AA) supplementation could be a promising approach to promote healthy fetal growth. PubMed, Embase and Cochrane libraries were searched to identify studies orally supplementing the following AA groups during gestation: (1) arginine family; (2) branched chain (BCAA); (3) methyl donors. Primary outcome was fetal/birth weight. 22 human and 89 animal studies were included in the systematic review. The arginine family, and especially arginine itself, was studied most. Our meta-analysis showed beneficial effects of arginine and (-Carbamyl) glutamate (NCG), but not aspartic acid and citrulline on fetal/birth weight. However, no effects were reported when isonitrogenous control diet was included. BCAA and methyl donor supplementation did not affect fetal/birth weight. Arginine family supplementation, in particular arginine and NCG, improves fetal growth in complicated pregnancies. BCAA and methyl donor supplementation do not seem to be as promising to target fetal growth. Well controlled research in complicated pregnancies is needed before ruling out AA supplements or preferring arginine above other AAs.
Topics: Amino Acids; Animals; Arginine; Birth Weight; Dietary Supplements; Female; Fetal Development; Fetal Growth Retardation; Glutamic Acid; Humans; Maternal Nutritional Physiological Phenomena; Maternal-Fetal Exchange; Pregnancy; Prenatal Nutritional Physiological Phenomena
PubMed: 32825593
DOI: 10.3390/nu12092535 -
Journal of Neurotrauma Nov 2022Magnetic resonance spectroscopy (MRS) is a non-invasive technique used to study metabolites in the brain. MRS findings in traumatic brain injury (TBI) and subconcussive... (Meta-Analysis)
Meta-Analysis Review
Magnetic resonance spectroscopy (MRS) is a non-invasive technique used to study metabolites in the brain. MRS findings in traumatic brain injury (TBI) and subconcussive hit literature have been mixed. The most common observation is a decrease in -acetyl-aspartate (NAA), traditionally considered a marker of neuronal integrity. Other metabolites, however, such as creatine (Cr), choline (Cho), glutamate+glutamine (Glx) and -inositol (mI) have shown inconsistent changes in these populations. The objective of this systematic review and meta-analysis was to synthesize MRS literature in brain injury and explore factors (biological factors such as brain region, injury severity, time since injury, demographics and technical methodological factors such as field strength, acquisition parameters, analysis approach) that may contribute to differential findings. One hundred and thirty-eight studies met inclusion criteria for the systematic review and of those, 62 NAA, 24 Cr, 49 Cho, 18 Glx, and 21 mI studies met inclusion criteria for meta-analysis. A random effects model was used for meta-analyses with brain region as a subgroup for each of the five metabolites studied. Meta-regression was used to examine the influence of potential moderators including injury severity, time since injury, age, sex, tissue composition, and methodological factors. In this analysis of 1428 unique brain-injured subjects and 1132 controls, the corpus callosum was identified as a brain region highly susceptible to metabolite alteration. NAA was consistently decreased in TBI of all severities, but not in subconcussive hits. Cho and mI were found to be increased in moderate-to-severe TBI but not in mild TBI. Glx and Cr were largely unaffected, but did show alterations in certain conditions.
Topics: Humans; Magnetic Resonance Spectroscopy; Aspartic Acid; Magnetic Resonance Imaging; Creatine; Brain Injuries, Traumatic; Brain Concussion; Brain; Choline; Inositol
PubMed: 35838132
DOI: 10.1089/neu.2022.0125 -
Frontiers in Neurology 2024This research aims to investigate whether peripheral biomarkers might differentiate individuals with Tourette syndrome (TS) from those without the condition.
OBJECTIVE
This research aims to investigate whether peripheral biomarkers might differentiate individuals with Tourette syndrome (TS) from those without the condition.
METHODS
A broad range of databases was searched through November 2022. This study employed a systematic literature review and subsequent meta-analysis of case-control studies that assessed the aberration of biomarkers of patients with TS and controls.
RESULTS
A total of 81 studies were identified, out of which 60 met the eligibility criteria for inclusion in the meta-analysis. Following a meticulous screening procedure to determine the feasibility of incorporating case-control studies into the meta-analysis, 13 comparisons were statistically significant [CD3+ T cell, CD4+ T cell, CD4+ T cell to CD8+ T cell ratio, NK-cell, anti-streptolysin O antibodies, anti-DNase antibodies, glutamic acid (Glu), aspartic acid (Asp), ferritin (Fe), zinc (Zn), lead (Pb), vitamin D, and brain-derived neurotrophic factor (BDNF)]. Publication bias was found for anti-streptolysin O antibodies. Suggestive associations were evidenced for norsalsolinol (NSAL), neuron-specific enolase (NSE), and S100B.
CONCLUSION
In this study, we present empirical evidence substantiating the link between several peripheral biomarkers and the early diagnosis of TS. Larger and more standardized studies are necessary to replicate the observed results, elucidate the specificity of the biomarkers for TS, and evaluate their precision for use in clinical settings.
PubMed: 38385037
DOI: 10.3389/fneur.2024.1262057 -
International Journal of Molecular... Aug 2022The exact neurobiological mechanisms of bipolar disorder (BD) remain unknown. However, some neurometabolites could be implicated, including Glutamate (Glu), Glutamine... (Meta-Analysis)
Meta-Analysis Review
The exact neurobiological mechanisms of bipolar disorder (BD) remain unknown. However, some neurometabolites could be implicated, including Glutamate (Glu), Glutamine (Gln), Glx, and N-acetylaspartate (NAA). Proton Magnetic Resonance Spectroscopy (H-MRS) allows one to quantify these metabolites in the human brain. Thus, we conducted a systematic review and meta-analysis of the literature to compare their levels between BD patients and healthy controls (HC). The main inclusion criteria for inclusion were H-MRS studies comparing levels of Glu, Gln, Glx, and NAA in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampi between patients with BD in clinical remission or a major depressive episode and HC. Thirty-three studies were included. NAA levels were significantly lower in the left white matter PFC (wmPFC) of depressive and remitted BD patients compared to controls and were also significantly higher in the left dorsolateral PFC (dlPFC) of depressive BD patients compared to HC. Gln levels were significantly higher in the ACC of remitted BD patients compared to in HC. The decreased levels of NAA of BD patients may be related to the alterations in neuroplasticity and synaptic plasticity found in BD patients and may explain the deep white matter hyperintensities frequently observed via magnetic resonance imagery.
Topics: Aspartic Acid; Bipolar Disorder; Depressive Disorder, Major; Glutamic Acid; Glutamine; Humans; Proton Magnetic Resonance Spectroscopy
PubMed: 36012234
DOI: 10.3390/ijms23168974 -
Psychiatry Research 2012This meta-analysis evaluates alterations of neurometabolites in schizophrenia and bipolar disorder. PubMed was searched to find controlled studies evaluating... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis evaluates alterations of neurometabolites in schizophrenia and bipolar disorder. PubMed was searched to find controlled studies evaluating N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr) assessed with ((1))H-MRS (proton magnetic resonance spectroscopy) in patients with schizophrenia and bipolar disorder up to September 2010. Random effects meta-analyses were conducted to estimate pooled standardized mean differences. The statistic was used to quantify inconsistencies. Subgroup analyses were conducted to explore potential explanations for inconsistencies. The systematic review included 146 studies with 5643 participants. NAA levels were affected in schizophrenia and bipolar disorder. Decreased levels in the basal ganglia and frontal lobe were the most consistent findings in schizophrenia; decreased levels in the basal ganglia were the most consistent findings in bipolar disorder. Cho and Cr levels were not altered in either disorder. Findings for Cr were most consistent in the thalamus, frontal lobe and dorsolateral prefrontal cortex in schizophrenia and the basal ganglia and frontal lobe in bipolar disorder. Findings for Cho were most consistent in the thalamus, frontal lobe and anterior cingulate cortex in schizophrenia and basal ganglia in bipolar disorder. Large, carefully designed studies are needed to better estimate the extent of alterations in neurometabolites.
Topics: Aspartic Acid; Basal Ganglia; Bipolar Disorder; Choline; Creatine; Gyrus Cinguli; Humans; Magnetic Resonance Spectroscopy; Prefrontal Cortex; Reference Values; Schizophrenia; Schizophrenic Psychology; Thalamus
PubMed: 22981426
DOI: 10.1016/j.pscychresns.2012.02.003 -
Asian Journal of Urology Apr 2024Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various... (Review)
Review
OBJECTIVE
Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.
METHODS
A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.
RESULTS
The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.
CONCLUSION
The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.
PubMed: 38680576
DOI: 10.1016/j.ajur.2022.11.005