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Implementation Science : IS Jul 2022Many strategies aimed at deprescribing benzodiazepine receptor agonists (BZRA) in older adults have already been evaluated with various success rates. There is so far no... (Review)
Review
Barriers and enablers for deprescribing benzodiazepine receptor agonists in older adults: a systematic review of qualitative and quantitative studies using the theoretical domains framework.
BACKGROUND
Many strategies aimed at deprescribing benzodiazepine receptor agonists (BZRA) in older adults have already been evaluated with various success rates. There is so far no consensus on which strategy components increase deprescribing the most. Yet, despite an unfavourable benefit-to-risk ratio, BZRA use among older adults remains high. We systematically reviewed barriers and enablers for BZRA deprescribing in older adults.
METHODS
Two reviewers independently screened records identified from five electronic databases-Medline, Embase, PsycINFO, CINAHL and the Cochrane library-and published before October 2020. They searched for grey literature using Google Scholar. Qualitative and quantitative records reporting data on the attitudes of older adults, caregivers and healthcare providers towards BZRA deprescribing were included. Populations at the end of life or with specific psychiatric illness, except for dementia, were excluded. The two reviewers independently assessed the quality of the included studies using the mixed-methods appraisal tool. Barriers and enablers were identified and then coded into domains of the theoretical domains framework (TDF) using a combination of deductive and inductive qualitative analysis. The most relevant TDF domains for BZRA deprescribing were then identified.
RESULTS
Twenty-three studies were included 13 quantitative, 8 qualitative and 2 mixed-method studies. The points of view of older adults, general practitioners and nurses were reported in 19, 9 and 3 records, respectively. We identified barriers and enablers in the majority of TDF domains and in two additional themes: "patient characteristics" and "BZRA prescribing patterns". Overall, the most relevant TDF domains were "beliefs about capabilities", "beliefs about consequences", "environmental context and resources", "intention", "goals", "social influences", "memory, attention and decision processes". Perceived barriers and enablers within domains differed across settings and across stakeholders.
CONCLUSION
The relevant TDF domains we identified can now be linked to behavioural change techniques to help in the design of future strategies and health policies. Future studies should also assess barriers and enablers perceived by under-evaluated stakeholders (such as pharmacists, psychiatrists and health care professionals in the hospital setting).
TRIAL REGISTRATION
This work was registered on PROSPERO under the title "Barriers and enablers to benzodiazepine receptor agonists deprescribing".
REGISTRATION NUMBER
CRD42020213035.
Topics: Aged; Deprescriptions; General Practitioners; Humans; Intention; Pharmacists; Qualitative Research; Receptors, GABA-A
PubMed: 35804428
DOI: 10.1186/s13012-022-01206-7 -
Biomolecules Jun 2022Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the... (Review)
Review
Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30-40% of patients, and characterized by serious cognitive deficits and functional impairment. In the present systematic review, we address with a direct and reverse translational perspective the efficacy of D-amino acids, including D-serine, D-aspartate, and D-alanine, in poor responders. The impact of these molecules on the synaptic architecture is also considered in the light of dendritic spine changes reported in schizophrenia and antipsychotics' effect on postsynaptic density proteins. Moreover, we describe compounds targeting D-amino acid oxidase and D-aspartate oxidase enzymes. Finally, other drugs acting at NMDAR and proxy of D-amino acids function, such as D-cycloserine, sarcosine, and glycine, are considered in the light of the clinical burden of TRS, together with other emerging molecules.
Topics: Amino Acids; Antipsychotic Agents; Humans; Neurobiology; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Schizophrenia, Treatment-Resistant
PubMed: 35883465
DOI: 10.3390/biom12070909 -
Drug Design, Development and Therapy 2018The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia (TD).
MATERIALS AND METHODS
We conducted a literature search in PubMed, Cochrane Database, and ClinicalTrials.gov, screening for systematic reviews, meta-analyses or double-blind, randomized, placebo-controlled trials (DBRPCTs) reporting efficacy or safety data of VMAT-2 inhibitors (tetrabenazine, deutetrabenazine, and valbenazine) in patients with TD. A random effects meta-analysis of efficacy and safety data from DBRPCTs was performed.
RESULTS
Two acute, 12-week DBRPCTs with deutetrabenazine 12-48 mg/day (n=413) and 4 acute, 4-6-week double-blind trials with valbenazine 12.5-100 mg/day (n=488) were meta-analyzable, without meta-analyzable, high-quality data for tetrabenazine. Regarding reduction in total Abnormal Involuntary Movement Scale (AIMS) scores (primary outcome), both deutetrabenazine (k=2, n=413, standardized mean difference [SMD] =-0.40, 95% confidence interval [CI] =-0.19, -0.62, <0.001; weighted mean difference (WMD) =-1.44, 95% CI =-0.67, -2.19, <0.001) and valbenazine (k=4, n=421, SMD =-0.58, 95% CI =-0.26, -0.91, <0.001; WMD =-2.07, 95% CI =-1.08, -3.05, <0.001) significantly outperformed placebo. Results were confirmed regarding responder rates (≥50% AIMS total score reduction; deutetrabenazine: risk ratio [RR] =2.13, 95% CI =1.10, 4.12, =0.024, number-needed-to-treat [NNT] =7, 95% CI =3, 333, =0.046; valbenazine: RR =3.05, 95% CI =1.81, 5.11, <0.001, NNT =4, 95% CI =3, 6, <0.001). Less consistent results emerged from patient-rated global impression-based response (=0.15) and clinical global impression for deutetrabenazine (=0.088), and for clinical global impression change for valbenazine (=0.67). In an open-label extension (OLE) study of deutetrabenazine (≤54 weeks) and a dose-blinded valbenazine study (≤48 weeks), responder rates increased over time. With valbenazine, discontinuation effects were studied, showing TD symptom recurrence towards baseline severity levels within 4 weeks after valbenazine withdrawal. No increased cumulative or specific adverse (AEs) events versus placebo (acute trials) in extension versus acute trial data were observed.
CONCLUSION
The 2 VMAT-2 inhibitors, valbenazine and deutetrabenazine, are effective in treating TD, both acutely and long-term, without concerns about increased risk of depression or suicide in the TD population. No head-to-head comparison among VMAT-2 inhibitors and no high-quality, meta-analyzable data are available for tetrabenazine in patients with TD.
Topics: Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 29795977
DOI: 10.2147/DDDT.S133205 -
Clinical Neurophysiology : Official... Jan 2020Measurement of axonal excitability provides an in vivo indication of the properties of the nerve membrane and of the ion channels expressed on these axons. Axonal...
Measurement of axonal excitability provides an in vivo indication of the properties of the nerve membrane and of the ion channels expressed on these axons. Axonal excitability techniques have been utilised to investigate the pathophysiological mechanisms underlying neurological diseases. This document presents guidelines derived for such studies, based on a consensus of international experts, and highlights the potential difficulties when interpreting abnormalities in diseased axons. The present manuscript provides a state-of-the-art review of the findings of axonal excitability studies and their interpretation, in addition to suggesting guidelines for the optimal performance of excitability studies.
Topics: Action Potentials; Axons; Consensus; Electric Stimulation; Electrodes, Implanted; Equipment Design; Humans; Ion Channels; Membrane Potentials; Models, Neurological; Nervous System Diseases; Neurophysiology; Sensory Thresholds; Software
PubMed: 31471200
DOI: 10.1016/j.clinph.2019.07.023 -
Oncotarget Jan 2017Karyopherin α2 (KPNA2), a member of the Karyopherin α family, has recently been reported to play an important role in tumor progression. However, the association... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Karyopherin α2 (KPNA2), a member of the Karyopherin α family, has recently been reported to play an important role in tumor progression. However, the association between KPNA2 expression and prognosis in cancer remains controversial. So we performed this meta-analysis to evaluate whether expression of KPNA2 was associated with prognosis in patients with solid tumor.
METHODS/FINDINGS
24 published eligible studies, including 6164 cases, were identified and included in this meta-analysis through searching of PubMed, EMBASE and Web of Science. We found that KPNA2 expression was an independent predictor for the prognosis of solid tumor with primary outcome (overall survival [OS]: pooled HR=1.767, 95% CI=1.503-2.077, P<0.001) and secondary outcomes (time to recurrence [TTR], recurrence free survival [RFS] and progression free survival [PFS]). However, the association between KPNA2 overexpression and disease free survival [DFS] in solid tumors was not significant (pooled HR=1.653, 95% CI=0.903-3.029, P=0.104). Furthermore, the subgroup analysis revealed that KPNA2 overexpression was associated with poor OS in East-Asian patients and European patients, as well as patients with gastric and colorectal cancer.
CONCLUSION
KPNA2 expression may be a useful prognostic biomarker to monitor cancer prognosis. Further prospective studies with larger sample sizes are required to confirm our findings.
Topics: Asian People; Biomarkers, Tumor; Colorectal Neoplasms; Disease-Free Survival; Humans; Neoplasm Recurrence, Local; Prognosis; Stomach Neoplasms; Up-Regulation; White People; alpha Karyopherins
PubMed: 27974678
DOI: 10.18632/oncotarget.13863 -
Medicine May 2017We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aimed to assess the safety and efficiency of the novel sodium glucose co-transporter 2 (SGLT2) inhibitor in combinations with insulin for type 1 and type 2 diabetes mellitus (T1DM and T2DM).
METHODS
We searched Medline, Pubmed, Embase, and the Cochrane Collaboration Library from January 2010 to December 2016 without restriction of language. FDA data and Clinical Trials (http://www.clinicaltrials.gov) were also searched. Study selection, data extraction, and evaluation of risk of bias were performed by 2 persons independently. The risk of bias was assessed by Cochrance System Evaluate Method and Q test was used to evaluate the heterogeneity between studies. We used random effect model to analyze the results by Revman 5.3. This meta-analysis has been registered at online public registry PROSPERO (registration number is: CRD42017054718).
RESULTS
Nine trials including 3069 patients were analyzed. Compared with control group, SGLT2 inhibitor produced absolute reduction in glycosylated hemoglobin A1c (HbA1c) (MD -1.35%, 95% confidence interval [CI] [-2.36 to -0.34], P = .009), fasting plasma glucose (FPG) (MD -1.01 mmol/L, 95%CI [-1.98 to 0.04], P = .04), insulin dosage (MD -4.85 U/24 hours, 95%CI [-7.42 to -2.29], P = .002), and body weight (MD -2.30 kg, 95%CI [-3.09 to -1.50], P < .00001). But the risk of hypoglycemia (OR 1.18, 95%CI [0.86, 1.61], P = . 30) and urinary tract infection (UTI) (OR 1.34, 95%CI [0.79, 2.27], P = .28) were proved as no difference and genital tract infection (GTI) with SGLT2 inhibitors was higher than control group (OR 2.96, 95%CI [1.05, 8.37], P = .04), in which cases were mild and responded to the therapy. According to the subgroup analysis, SGLT2 inhibitors had a similar effect in effective factors of both T1DM and T2DM, but the risk of GTI mainly increased in T2DM versus T1DM (T1DM OR 0.27 [0.01, 7.19], P = .43 vs T2DM OR 4.28 [2.00, 9.16], P = .0002).
CONCLUSION
SGLT2 inhibitors have improved the HbA1c, FPG, and body weight when combined with insulin and decreased the dose of insulin without increasing the risk of hypoglycemia. However, SGLT2 inhibitor was proved to be related to the events of GTI, despite SGLT2 inhibitors appeared to be well tolerated. We suggest that more monitoring should be done to prevent the events of GTI, and more randomized controlled trials should be planned next step.
Topics: Diabetes Mellitus; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 28538386
DOI: 10.1097/MD.0000000000006944 -
Oncotarget Feb 2017The role of glucose transporters in cancers remains contradictory. We conducted a systematic review and meta-analysis to assess the association between overall survival... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
The role of glucose transporters in cancers remains contradictory. We conducted a systematic review and meta-analysis to assess the association between overall survival and glucose transporter s (GLUTs) 1 and 3 to find an accurate prognostic biomarker.
METHODS
We systematically searched the PubMed, EMbase and Medline databases for relevant published studies that were consistent with the eligible criteria up to January 2016, and calculated pooled estimated hazard ratios of GLUT-1 and -3's expressions in different cancer types and ethnic populations. Random-effects models were used to assess estimates from studies with significant heterogeneities.
RESULTS
Overall, 12 studies concerning GLUT 1 and 2 studies concerning GLUT 3, which involved 2008 participants when combined, were included in this analysis. We found that overexpression of GLUTs were significantly correlated to poorer survival rates (HR=1.63, 95%CI=1.09-2.44 and HR=1.89, 95%CI=1.28-2.81). In the subgroup analysis, the GLUT 1 up-regulation was correlated with negative overall survival in pancreatic cancer and gastric cancer and with better overall survival in colorectal cancer. In addition, overexpression of GLUT 1 was associated with a poorer prognosis in the Asian population, while no significance was found in the non-Asian subgroup. However, limitations do exist, which could be handled better.
CONCLUSIONS
A combination of GLUTs 1 and 3 might help predict malignancy of cancers and direct effective cancer therapy.
Topics: Asian People; Biomarkers, Tumor; Glucose Transporter Type 1; Glucose Transporter Type 3; Humans; Neoplasms; Predictive Value of Tests; Prognosis; Survival Analysis
PubMed: 28086215
DOI: 10.18632/oncotarget.14570 -
Toxins Apr 2020Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of...
Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of low-molecular-weight peptide toxins that have evolved to target voltage-gated ion channels to interfere with the central system of prey and produce pain or paralysis for efficient hunting. Peptide toxins usually contain several intramolecular disulfide bonds, which confer chemical, thermal and biological stability. In addition, centipede peptides generally have novel structures and high potency and specificity and therefore hold great promise both as diagnostic tools and in the treatment of human disease. Here, we review the centipede peptide toxins with reported effects on ion channels, including Nav, Kv, Cav and the nonselective cation channel polymodal transient receptor potential vanilloid 1 (TRPV1).
Topics: Animals; Arthropod Proteins; Arthropod Venoms; Bites and Stings; Chilopoda; Drug Discovery; Humans; Ion Channels; Membrane Transport Modulators; Protein Conformation; Signal Transduction; Structure-Activity Relationship
PubMed: 32260499
DOI: 10.3390/toxins12040230 -
BMC Neurology Feb 2017Antiepileptic drugs (AEDs) are effective medications available for epilepsy. However, many patients do not respond to this treatment and become resistant. Genetic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antiepileptic drugs (AEDs) are effective medications available for epilepsy. However, many patients do not respond to this treatment and become resistant. Genetic polymorphisms may be involved in the variation of AEDs response. Therefore, we conducted an updated systematic review and a meta-analysis to investigate the contribution of the genetic profile on epilepsy drug resistance.
METHODS
We proceeded to the selection of eligible studies related to the associations of polymorphisms with resistance to AEDs therapy in epilepsy, published from January 1980 until November 2016, using Pubmed and Cochrane Library databases. The association analysis was based on pooled odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
From 640 articles, we retained 13 articles to evaluate the relationship between ATP-binding cassette sub-family C member 1 (ABCB1) C3435T polymorphism and AEDs responsiveness in a total of 454 epileptic AEDs-resistant cases and 282 AEDs-responsive cases. We found a significant association with an OR of 1.877, 95% CI 1.213-2.905. Subanalysis by genotype model showed a more significant association between the recessive model of ABCB1 C3435T polymorphism (TT vs. CC) and the risk of AEDs resistance with an OR of 2.375, 95% CI 1.775-3.178 than in the dominant one (CC vs. TT) with an OR of 1.686, 95% CI 0.877-3.242.
CONCLUSION
Our results indicate that ABCB1 C3435T polymorphism, especially TT genotype, plays an important role in refractory epilepsy. As genetic screening of this genotype may be useful to predict AEDs response before starting the treatment, further investigations should validate the association.
Topics: ATP Binding Cassette Transporter, Subfamily B; Anticonvulsants; Drug Resistance; Epilepsy; Genotype; Humans; Polymorphism, Single Nucleotide
PubMed: 28202008
DOI: 10.1186/s12883-017-0801-x -
International Journal of Clinical... 2022The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this study was to clarify the role of genetic factors on posttransplant diabetes mellitus (PTDM) risk.
METHODS
Relevant publications were systematically retrieved from PubMed, EMBASE, and the Cochrane Library up to December 2020. Data from eligible case-control and cohort studies were extracted for qualitative and quantitative analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between gene polymorphisms and PTDM in the quantitative meta-analysis.
RESULTS
A total of 43 eligible articles were identified, and 16 studies on 9 DNA variants from 8 genes were included in the meta-analysis. rs7903146 was significantly associated with PTDM risk in 5 genetic models (OR (95% CI): allelic: 1.59 (1.17-2.16), =0.003; dominant recessive: 1.62 (1.14, 2.31), =0.007; recessive: 1.87 (1.18, 2.94), =0.007; homozygote: 2.21 (1.23, 3.94), =0.008; and heterozygote 1.50 (1.08, 2.10), =0.017). rs2237892 was significantly correlated with PTDM risk in 3 genetic models (allelic: 0.68 (0.58, 0.81), < 0.001; dominant: 0.6 (049, 0.74), < 0.001; and heterozygote: 0.61 (0.48, 0.76), < 0.001). rs5219 was significantly linked with PTDM in the recessive genetic model (1.59 (1.01, 2.50), =0.047). No significant correlations of PTDM with rs12255372, rs13266634, rs1801282, rs10811661, rs1111875, and rs4402960 polymorphisms were found.
CONCLUSIONS
The gene polymorphisms of rs7903146, rs2237892, and rs5219 may predispose kidney transplant recipients to PTDM. Large sample size studies on diverse ethnic populations were warranted to confirm our findings.
Topics: Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Humans; KCNQ1 Potassium Channel; Kidney; Polymorphism, Single Nucleotide; RNA-Binding Proteins
PubMed: 35685576
DOI: 10.1155/2022/7140024