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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 -
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 -
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 -
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 -
Journal of Diabetes Research 2020Sub-Saharan Africa (SSA) is observing an accelerating prevalence rate of type 2 diabetes mellitus (T2DM) influenced by gene-environment interaction of modifiable and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Sub-Saharan Africa (SSA) is observing an accelerating prevalence rate of type 2 diabetes mellitus (T2DM) influenced by gene-environment interaction of modifiable and nonmodifiable factors. We conducted a systematic review and meta-analysis on the heritability and genetic risk of T2DM in SSA.
METHODS
We reviewed all published articles on T2DM in SSA between January 2000 and December 2019 and available in PubMed, Scopus, and Web of Science. Studies that reported on the genetics and/or heritability of T2DM or indicators of glycaemia were included. Data extracted included the study design, records of family history, pattern and characteristics of inheritance, genetic determinants, and effects estimates.
RESULTS
The pattern and characteristics of T2DM heritability in SSA are preference for maternal aggregation, higher among first degree compared to second-degree relatives; early age-onset (<50 years), and inherited abnormalities of beta-cell function/mass. The overall prevalence of T2DM was 28.2% for the population with a positive family history (PFH) and 11.2% for the population with negative family history (NFH). The pooled odds ratio of the impact of PFH on T2DM was 3.29 (95% CI: 2.40-4.52). Overall, 28 polymorphisms in 17 genes have been investigated in relation with T2DM in SSA. Almost all studies used the candidate gene approach with most (45.8%) of genetic studies published between 2011 and 2015. Polymorphisms in , , , , , , and were found to be associated with T2DM, with overlapping effect on specific cardiometabolic traits. Genome-wide studies identified ancestry-specific signals (, , and ) and as the only transferable genetic risk variants to SSA population. polymorphism was investigated in multiple studies with consistent effects and low-moderate statistical heterogeneity. Effect sizes were modestly strong [odds ratio = 6.17 (95% CI: 2.03-18.81), codominant model; 2.27 (95% CI: 1.50-3.44), additive model; 1.75 (95% CI: 1.18-2.59), recessive model]. Current evidence on the heritability and genetic markers of T2DM in SSA populations is limited and largely insufficient to reliably inform the genetic architecture of T2DM across SSA regions.
Topics: Adiponectin; Africa South of the Sahara; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Haptoglobins; Humans; Phosphoric Diester Hydrolases; Polymorphism, Single Nucleotide; Potassium Channels, Inwardly Rectifying; Pyrophosphatases; Sulfonylurea Receptors; Transcription Factor 7-Like 2 Protein; Tumor Necrosis Factor-alpha
PubMed: 32685554
DOI: 10.1155/2020/3198671 -
International Journal of Molecular... Mar 2023Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to... (Review)
Review
Energy production by cancer is driven by accelerated glycolysis, independently of oxygen levels, which results in increased lactate production. Lactate is shuttled to and from cancer cells via monocarboxylate transporters (MCTs). MCT1 works both as an importer and an extruder of lactate, being widely studied in recent years and generally associated with a cancer aggressiveness phenotype. The aim of this systematic review was to assess the prognostic value of MCT1 immunoexpression in different malignancies. Study collection was performed by searching nine different databases (PubMed, EMBASE, ScienceDirect, Scopus, Cochrane Library, Web of Science, OVID, TRIP and PsycINFO), using the keywords "cancer", "Monocarboxylate transporter 1", "SLC16A1" and "prognosis". Results showed that MCT1 is an indicator of poor prognosis and decreased survival for cancer patients in sixteen types of malignancies; associations between the transporter's overexpression and larger tumour sizes, higher disease stage/grade and metastasis occurrence were also frequently observed. Yet, MCT1 overexpression correlated with better outcomes in colorectal cancer, pancreatic ductal adenocarcinoma and non-small cell lung cancer patients. These results support the applicability of MCT1 as a biomarker of prognosis, although larger cohorts would be necessary to validate the overall role of MCT1 as an outcome predictor.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lactic Acid; Lung Neoplasms; Monocarboxylic Acid Transporters; Pancreatic Neoplasms; Prognosis; Symporters
PubMed: 36982217
DOI: 10.3390/ijms24065141 -
Tremor and Other Hyperkinetic Movements... 2024Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter... (Comparative Study)
Comparative Study Review
BACKGROUND
Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This study aims to compare the efficacy and safety profile of VMAT2 inhibitors, focusing on a recent trial conducted in the Asian population.
METHODS
We reviewed the PubMed, Cochrane Library, Embase database, and clinicaltrials.gov between January 2017 and October 2023, using the keywords "tardive dyskinesia" AND ("valbenazine" [all fields] OR " deutetrabenazine " [all fields]) AND "clinical trial". The reviewed articles were studied for efficacy and side effects.
RESULTS
An initial search yielded 230 articles, of which 104 were duplicates. Following the title and abstract screening, 25 additional articles were excluded. A full-text review resulted in the exclusion of 96 more articles. Ultimately, four double-blind clinical trials met the inclusion criteria. The deutetrabenazine studies demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo, with no difference in adverse events. The valbenazine studies showed favorable results in reducing TD symptoms and were well-tolerated.
DISCUSSION
The studies reviewed in this analysis underscore the potential of deutetrabenazine and valbenazine as valuable treatment options for TD in diverse populations. Both medications demonstrated significant improvements in AIMS scores, suggesting their effectiveness in managing TD symptoms. Additionally, they exhibited favorable safety profiles, with low rates of serious adverse events and no significant increase in QT prolongation, parkinsonism, suicidal ideation, or mortality.
CONCLUSION
The studies reviewed highlight the promising efficacy and tolerability of deutetrabenazine and valbenazine as treatments for Tardive Dyskinesia, providing new hope for individuals affected by this challenging condition.
Topics: Humans; Randomized Controlled Trials as Topic; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 38497033
DOI: 10.5334/tohm.842 -
International Journal of Environmental... Mar 2022The current systematic review examines whether there is an association between the genetic 5-HTTPLR polymorphism and parenting, and the mechanisms by which this... (Review)
Review
The current systematic review examines whether there is an association between the genetic 5-HTTPLR polymorphism and parenting, and the mechanisms by which this association operates. The literature was searched in various databases such as PubMed, Scopus, and ScienceDirect. In line with our inclusion criteria, nine articles were eligible out of 22. Most of the studies analysed in this review found an association between 5HTTLPR and parenting. Four studies found a direct association between 5-HTTLPR and parenting with conflicting findings: two studies found that mothers carrying the short variant were more sensitive to their infants, while two studies found that parents carrying the S allele were less sensitive. In addition, several studies found strong interaction between genetic and environmental factors, such as childhood stress and disruptive child behaviour, quality of early care experiences, poor parenting environment, and quality of the environment. Only one study found an association between children's 5HTTLPR and parenting. Parenting can be described as a highly complex construct influenced by multiple factors, including the environment, as well as parent and child characteristics. According to the studies, maternal 5-HTTLPR polymorphism is most likely to be associated with sensitive parenting.
Topics: Child; Female; Humans; Infant; Mothers; Parenting; Polymorphism, Genetic; Problem Behavior; Serotonin Plasma Membrane Transport Proteins
PubMed: 35409736
DOI: 10.3390/ijerph19074052 -
Molecular Psychiatry Jan 2022Brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a... (Review)
Review
Brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose. We aimed to systematically review the evidence on the relationship between antidepressant dose and SERT occupancy. We searched PubMed and Embase (last search 20 May 2021) for human in vivo, within-subject PET, or SPECT studies measuring SERT occupancy at any dose of any antidepressant with highly selective radioligands ([C]-DASB, [I]-ADAM, and [C]-MADAM). We summarized and visualized the dose-occupancy relationship for antidepressants across studies, overlaying the plots with a curve based on predicted values of a standard 2-parameter Michaelis-Menten model fitted using the observed data. We included seventeen studies of 10 different SSRIs, SNRIs, and serotonin modulators comprising a total of 294 participants, involving 309 unique occupancy measures. Overall, following the Michaelis-Menten equation, SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose. All the studies were small, only a few investigated the same antidepressant, dose, and brain region, and few reported information on factors that may influence SERT occupancy. The hyperbolic dose-occupancy relationship may provide mechanistic insight of relevance to the limited clinical benefit of dose-escalation in antidepressant treatment and the potential emergence of withdrawal symptoms. The evidence is limited by non-transparent reporting, lack of standardized methods, small sample sizes, and short treatment duration. Future studies should standardize the imaging and reporting procedures, measure occupancy at lower antidepressant doses, and investigate the moderators of the dose-occupancy relationship.
Topics: Antidepressive Agents; Brain; Citalopram; Humans; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors
PubMed: 34548628
DOI: 10.1038/s41380-021-01285-w -
Molecular Neurobiology Oct 2022Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between... (Review)
Review
Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.
Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is the link between the inflammatory background and two well-recognized functional and structural findings of schizophrenia pathophysiology: the dopamine-glutamate aberrant interaction and the alteration of dendritic spines architecture, both believed to be the "quantal" elements of cortical-subcortical dysfunctional network. In this systematic review, we tried to capture the major findings linking inflammation, aberrant glutamate-dopamine interaction, and post-synaptic changes under a direct and inverse translational perspective, a paramount picture that at present is lacking. The inflammatory effects on dopaminergic function appear to be bidirectional: the inflammation influences dopamine release, and dopamine acts as a regulator of discrete inflammatory processes involved in schizophrenia such as dysregulated interleukin and kynurenine pathways. Furthermore, the link between inflammation and glutamate is strongly supported by clinical studies aimed at exploring overactive microglia in schizophrenia patients and maternal immune activation models, indicating impaired glutamate regulation and reduced N-methyl-D-aspartate receptor (NMDAR) function. In addition, an inflammatory/immune-induced alteration of post-synaptic density scaffold proteins, crucial for downstream NMDAR signaling and synaptic efficacy, has been demonstrated. According to these findings, a significant increase in plasma inflammatory markers has been found in schizophrenia patients compared to healthy controls, associated with reduced cortical integrity and functional connectivity, relevant to the cognitive deficit of schizophrenia. Finally, the link between altered inflammatory/immune responses raises relevant questions regarding potential new therapeutic strategies specifically for those forms of schizophrenia that are resistant to canonical antipsychotics or unresponsive to clozapine.
Topics: Antipsychotic Agents; Dopamine; Glutamic Acid; Humans; Inflammation; Receptors, N-Methyl-D-Aspartate; Schizophrenia
PubMed: 35963926
DOI: 10.1007/s12035-022-02976-3