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ERJ Open Research Apr 2019Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function in PCD patients... (Review)
Review
Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function in PCD patients range from normal to severe impairment. This systematic review and meta-analysis of studies of lung function in PCD patients examines the spirometric indices of PCD patients and differences by age group and sex. We searched PubMed, Embase and Scopus for studies that described lung function in 10 or more patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity. We included 24 studies, ranging from 13 to 158 patients per study. The most commonly reported spirometric indices were forced expiratory volume in 1 s (FEV) and forced vital capacity presented as mean and standard deviation of percent predicted values. We found considerable heterogeneity for both parameters ( =94-96%). The heterogeneity remained when we stratified the analysis by age; however, FEV in adult patients was lower. Even after taking into account explanatory factors, the largest part of the between-studies variance remained unexplained. Heterogeneity could be explained by genetic differences between study populations, methodological factors related to the variability of study inclusion criteria or details on the performance and evaluation of lung function measurements that we could not account for. Prospective studies therefore need to use standardised protocols and international reference values. These results underline the possibility of distinct PCD phenotypes as in other chronic respiratory diseases. Detailed characterisation of these phenotypes and related genotypes is needed in order to better understand the natural history of PCD.
PubMed: 31111042
DOI: 10.1183/23120541.00231-2018 -
The Cochrane Database of Systematic... May 2015Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are... (Review)
Review
BACKGROUND
Agitation is a common experience for people living with dementia, particularly as day-to-day function and cognition start to decline more. At the present time there are limited pharmacological options for relieving agitation and little is known about the safety and efficacy of opioid drugs in this setting.
OBJECTIVES
To determine the clinical efficacy and safety of opioids for agitation in people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 13 June 2014 using the terms: narcotic OR opioid OR opium OR morphine OR buprenorphine OR codeine OR dextromoramide OR diphenoxylate OR dipipanone OR dextropropoxyphene OR propoxyphene OR diamorphine OR dihydrocodeine OR alfentanil OR fentanyl OR remifentanil OR meptazinol OR methadone OR nalbuphine OR oxycodone OR papaveretum OR pentazocine OR meperidine OR pethidine OR phenazocine OR hydrocodone OR hydromorphone OR levorphanol OR oxymorphone OR butorphanol OR dezocine OR sufentanil OR ketobemidone.ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases such as MEDLINE, EMBASE and PscyINFO, as well as numerous trial registries and grey literature sources.
SELECTION CRITERIA
Randomised, controlled trials of opioids compared to placebo for agitation in people with dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the studies identified by the search against the inclusion criteria.
MAIN RESULTS
There are currently no completed randomised, placebo controlled trials of opioids for agitation in dementia. There are two potentially relevant trials still in progress.
AUTHORS' CONCLUSIONS
We found insufficient evidence to establish the clinical efficacy and safety of opioids for agitation in people with dementia. There remains a lack of data to determine if or when opioids either relieve or exacerbate agitation. More evidence is needed to guide the effective, appropriate and safe use of opioids in dementia.
Topics: Analgesics, Opioid; Dementia; Humans; Psychomotor Agitation
PubMed: 25972091
DOI: 10.1002/14651858.CD009705.pub2 -
Human Mutation Sep 2022The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues.... (Review)
Review
The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues. Recent advances in whole-genome sequencing of patients with undiagnosed genetic disorders have identified several rare pathogenic variants in DOCK genes. We conducted a systematic review and performed a patient database and literature search of reported DOCK pathogenic variants that have been identified in association with clinical pathologies such as global developmental delay, immune cell dysfunction, muscle hypotonia, and muscle ataxia among other categories. We then categorized these pathogenic DOCK variants and their associated clinical phenotypes under several unique categories: developmental, cardiovascular, metabolic, cognitive, or neuromuscular. Our systematic review of DOCK variants aims to identify and analyze potential DOCK-regulated networks associated with neuromuscular diseases and other disease pathologies, which may identify novel therapeutic strategies and targets. This systematic analysis and categorization of human-associated pathologies with DOCK pathogenic variants is the first report to the best of our knowledge for a unique class in this understudied gene family that has important implications in furthering personalized genomic medicine, clinical diagnoses, and improve targeted therapeutic outcomes across many clinical pathologies.
Topics: Ataxia; Genomics; Guanine Nucleotide Exchange Factors; Humans; Intellectual Disability; Multigene Family; Muscle Hypotonia; Transcription Factors
PubMed: 35544951
DOI: 10.1002/humu.24398 -
Therapeutic Advances in... 2019Recent reports state that the prevalence of tardive dyskinesia (TD) is 32% with typical antipsychotics, and 13% with atypical antipsychotics. Current evidence-based... (Review)
Review
Recent reports state that the prevalence of tardive dyskinesia (TD) is 32% with typical antipsychotics, and 13% with atypical antipsychotics. Current evidence-based recommendations determine an unmet need for efficacious treatment of TD. This systematic review was planned to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine (DBZ), and valbenazine (VBZ). Of 75 PubMed search results, 11 studies met the review criteria. Efficacy and tolerability were demonstrated in a series of randomized, placebo-controlled clinical trials in our review study, and the Abnormal Involuntary Movement Scale response of ⩾50% reduction in score was robust for VBZ 80 mg/day in short-term and long-term studies. On the contrary, DBZ was equally efficacious at 12 mg twice daily, but additional information about long-term efficacy and persistence of effect is needed.
PubMed: 31205680
DOI: 10.1177/2045125319847882 -
The Cochrane Database of Systematic... Apr 2017Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is... (Review)
Review
BACKGROUND
Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is sustained.De-escalation is a psychosocial intervention for managing people with disturbed or aggressive behaviour. Secondary management strategies such as rapid tranquillisation, physical intervention and seclusion should only be considered once de-escalation and other strategies have failed to calm the service user.
OBJECTIVES
To investigate the effects of de-escalation techniques in the short-term management of aggression or agitation thought or likely to be due to psychosis.
SEARCH METHODS
We searched Cochrane Schizophrenia Group's Study-Based Register of Trials (latest search 7 April, 2016).
SELECTION CRITERIA
Randomised controlled trials using de-escalation techniques for the short-term management of aggressive or agitated behaviour. We planned to include trials involving adults (at least 18 years) with a potential for aggressive behaviour due to psychosis, from those in a psychiatric setting to those possibly under the influence of alcohol or drugs and/or as part of an acute setting as well. We planned to include trials meeting our inclusion criteria that provided useful data.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Two review authors inspected all abstracts of studies identified by the search process. As we were unable to include any studies, we could not perform data extraction and analysis.
MAIN RESULTS
Of the 345 citations that were identified using the search strategies, we found only one reference to be potentially suitable for further inspection. However, after viewing the full text, it was excluded as it was not a randomised controlled trial.
AUTHORS' CONCLUSIONS
Using de-escalation techniques for people with psychosis induced aggression or agitation appears to be accepted as good clinical practice but is not supported by evidence from randomised trials. It is unclear why it has remained such an under-researched area. Conducting trials in this area could be influenced by funding flow, ethical concerns - justified or not - anticipated pace of recruitment as well the difficulty in accurately quantifying the effects of de-escalation itself. With supportive funders and ethics committees, imaginative trialists, clinicians and service-user groups and wide collaboration this dearth of randomised research could be addressed.
Topics: Aggression; Behavior Control; Crisis Intervention; Humans; Psychomotor Agitation; Psychotic Disorders
PubMed: 28368091
DOI: 10.1002/14651858.CD009922.pub2 -
The Cochrane Database of Systematic... Jun 2017Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe... (Review)
Review
BACKGROUND
Chronic idiopathic axonal polyneuropathy (CIAP) is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, CIAP reduces quality of life. CIAP is diagnosed in 10% to 25% of people referred for evaluation of polyneuropathy. There is a need to gather and review emerging evidence on treatments, as the number of people affected is likely to increase in ageing populations. This is an update of a review first published in 2004 and previously updated in 2006, 2008, 2011 and 2013.
OBJECTIVES
To assess the effects of drug therapy for chronic idiopathic axonal polyneuropathy for reducing disability and ameliorating neurological symptoms and associated impairments, and to assess any adverse effects of treatment.
SEARCH METHODS
In July 2016, we searched Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews in the Cochrane Library, MEDLINE, Embase, and the Web of Science. We searched two trials registries for ongoing trials. We also handsearched the reference lists of relevant articles, reviews and textbooks identified electronically, and we would have contacted authors and other experts in the field to identify additional studies if this seemed useful.
SELECTION CRITERIA
We sought all randomised or quasi-randomised (alternate or other systematic treatment allocation) trials that examined the effects of any drug therapy in people with CIAP at least one year after the onset of treatment. People with CIAP had to fulfil the following criteria: age 40 years or older, distal sensory or sensorimotor polyneuropathy, absence of systemic or other neurological disease, chronic clinical course not reaching a nadir in less than two months, exclusion of any recognised cause of the polyneuropathy by medical history taking, clinical or laboratory investigations, and electrophysiological studies in agreement with axonal polyneuropathy, without evidence of demyelinating features. The primary outcome was the proportion of participants with a significant improvement in disability. Secondary outcomes were change in the mean disability score, change in the proportion of participants who make use of walking aids, change in the mean Medical Research Council sum score, degree of pain relief and/or reduction of other positive sensory symptoms, change in the proportion of participants with pain or other positive sensory symptoms, and frequency of adverse effects.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the results of the literature search and extracted details of trial methodology and outcome data of all potentially relevant trials.
MAIN RESULTS
We identified 39 studies and assessed them for possible inclusion in the review, but we excluded all of them because of insufficient quality or lack of relevance. We summarised evidence from non-randomised studies in the Discussion.
AUTHORS' CONCLUSIONS
Even though CIAP has been clearly described and delineated, no adequate randomised or quasi-randomised controlled clinical treatment trials have been performed. In their absence there is no proven efficacious drug therapy.
Topics: Aged; Axons; Chronic Disease; Gait Ataxia; Humans; Leg; Polyneuropathies
PubMed: 28631805
DOI: 10.1002/14651858.CD003456.pub3 -
Brain Research Bulletin Oct 2023Gait analysis could be used in animal models as an indicator of sensory ataxia due to chemotherapy-induced peripheral neurotoxicity (CIPN). Over the years, gait analysis... (Review)
Review
Gait analysis could be used in animal models as an indicator of sensory ataxia due to chemotherapy-induced peripheral neurotoxicity (CIPN). Over the years, gait analysis in in vivo studies has evolved from simple observations carried out by a trained operator to computerised systems with machine learning that allow the quantification of any variable of interest and the establishment of algorithms for behavioural classification. However, there is not a consensus on gait analysis use in CIPN animal models; therefore, we carried out a systematic review. Of 987 potentially relevant studies, 14 were included, in which different methods were analysed (observation, footprint and CatWalk™). We presented the state-of-the-art of possible approaches to analyse sensory ataxia in rodent models, addressing advantages and disadvantages of different methods available. Semi-automated methods may be of interest when preventive or therapeutic strategies are evaluated, also considering their methodological simplicity and automaticity; up to now, only CatWalk™ analysis has been tested. Future studies should expect that CIPN-affected animals tend to reduce hind paw support due to pain, allodynia or loss of sensation, and an increase in swing phase could or should be observed. Few available studies documented these impairments at the last time point, and only appeared later on respect to other earlier signs of CIPN (such as altered neurophysiological findings). For that reason, gait impairment could be interpreted as late repercussions of loss of sensory.
Topics: Animals; Peripheral Nervous System Diseases; Gait Analysis; Rodentia; Neurotoxicity Syndromes; Antineoplastic Agents; Ataxia
PubMed: 37748696
DOI: 10.1016/j.brainresbull.2023.110769 -
Frontiers in Neurology 2023Autoimmune encephalitis (AE) is an increasingly recognized neuroinflammatory disease entity in which early detection and treatment leads to the best clinical outcomes....
BACKGROUND
Autoimmune encephalitis (AE) is an increasingly recognized neuroinflammatory disease entity in which early detection and treatment leads to the best clinical outcomes. Movement disorders occur in AE but their characteristics are not well defined.
OBJECTIVES
To identify the frequency, classification, and prognostic significance of movement disorders in AE.
METHODS
We conducted a systematic review and random-effects meta-analysis of movement disorders in cell surface antibody mediated AE. The frequency of any movement disorder as well as the classification of movement disorders in AE serotypes was determined. We looked at adults 18 years and older and included publications that described at least 10 cases. We used the following four electronic databases: Medline (Ovid), EMBASE (Ovid), APA Psychinfo, and Cochrane library.
RESULTS
A total of 1,192 titles and abstracts were reviewed. Thirty-seven studies were included in the final meta-analysis. At least one kind of movement disorder was present in 40% of the entire AE cohort, 53% with anti-NMDA receptor antibodies, 33% with anti-CASPR2 antibodies, 30% with anti-LGI1 antibodies and 13% with anti-GABA receptor antibodies. Dyskinesia was the commonest movement disorder in anti-NMDA antibody mediated AE and faciobrachial dystonic seizures were most frequent in anti-LGI1 antibody mediated AE. Patients with a movement disorder tended to have a higher mortality. The risk of bias in the included studies was mostly moderate or high.
CONCLUSION
Movement disorders are common in AE and their identification, in conjunction with other clinical and paraclinical features, may facilitate earlier diagnosis. The prognostic implications of movement disorders in AE warrant further dedicated study.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42023386920.
PubMed: 37545714
DOI: 10.3389/fneur.2023.1225523 -
Biomedicine & Pharmacotherapy =... Sep 2023Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs... (Review)
Review
Neurodegenerative diseases (NDDs) encompass a range of conditions that involve progressive deterioration and dysfunction of the nervous system. Some of the common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Although significant progress has been made in understanding the pathological mechanisms of NDDs in recent years, the development of targeted and effective drugs for their treatment remains challenging. Kaempferol is a flavonoid whose derivatives include kaempferol-O-rhamnoside, 3-O-β-rutinoside/6-hydroxykaempferol 3,6-di-O-β-d-glucoside, and kaempferide. Emerging studies have suggested that kaempferol and its derivatives possess neuroprotective properties and may have potential therapeutic benefits in NDDs. Here, we aimed to provide a theoretical basis for the use of kaempferol and its derivatives in the clinical treatment of NDDs. We systematically reviewed the literature in the PubMed, Web of Science, and Science Direct databases until June 2022 using the search terms "kaempferol," "kaempferol derivatives," "NDDs," "pharmacokinetics," and "biosynthesis" according to the reporting items for systematic review (PRISMA) standard. Based on combined results of in vivo and in vitro studies, we summarize the basic mechanisms and targets of kaempferol and its derivatives in the management of AD, PD, HD, and ALS. Kaempferol and its derivatives exert a neuroprotective role mainly by preventing the deposition of amyloid fibrils (such as Aβ, tau, and α-synuclein), inhibiting microglia activation, reducing the release of inflammatory factors, restoring the mitochondrial membrane to prevent oxidative stress, protecting the blood-brain barrier, and inhibiting specific enzyme activities (such as cholinesterase). Kaempferol and its derivatives are promising natural neuroprotective agents. By determining their pharmacological mechanism, kaempferol and its derivatives may be new candidate drugs for the treatment of NDDs.
Topics: Humans; Neurodegenerative Diseases; Neuroprotective Agents; Amyotrophic Lateral Sclerosis; Kaempferols; Alzheimer Disease; Parkinson Disease; Huntington Disease
PubMed: 37494786
DOI: 10.1016/j.biopha.2023.115215 -
The Cochrane Database of Systematic... Jan 2018Tardive dyskinesia (TD) is a disfiguring movement disorder, often of the orofacial region, frequently caused by using antipsychotic drugs. A wide range of strategies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tardive dyskinesia (TD) is a disfiguring movement disorder, often of the orofacial region, frequently caused by using antipsychotic drugs. A wide range of strategies have been used to help manage TD, and for those who are unable to have their antipsychotic medication stopped or substantially changed, the benzodiazepine group of drugs have been suggested as a useful adjunctive treatment. However, benzodiazepines are very addictive.
OBJECTIVES
To determine the effects of benzodiazepines for antipsychotic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder, or other chronic mental illnesses.
SEARCH METHODS
On 17 July 2015 and 26 April 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers), inspected references of all identified studies for further trials and contacted authors of each included trial for additional information.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) focusing on people with schizophrenia (or other chronic mental illnesses) and antipsychotic-induced TD that compared benzodiazepines with placebo, no intervention, or any other intervention for the treatment of TD.
DATA COLLECTION AND ANALYSIS
We independently extracted data from the included studies and ensured that they were reliably selected, and quality assessed. For homogenous dichotomous data, we calculated random effects, risk ratio (RR), and 95% confidence intervals (CI). We synthesised continuous data from valid scales using mean differences (MD). For continuous outcomes, we preferred endpoint data to change data. We assumed that people who left early had no improvement.
MAIN RESULTS
The review now includes four trials (total 75 people, one additional trial since 2006, 21 people) randomising inpatients and outpatients in China and the USA. Risk of bias was mostly unclear as reporting was poor. We are uncertain about all the effects as all evidence was graded at very low quality. We found no significant difference between benzodiazepines and placebo for the outcome of 'no clinically important improvement in TD' (2 RCTs, 32 people, RR 1.12, 95% CI 0.60 to 2.09, very low quality evidence). Significantly fewer participants allocated to clonazepam compared with phenobarbital (as active placebo) experienced no clinically important improvement (RR 0.44, 95% CI 0.20 to 0.96, 1 RCT, 21 people, very low quality evidence). For the outcome 'deterioration of TD symptoms,' we found no clear difference between benzodiazepines and placebo (2 RCTs, 30 people, RR 1.48, 95% CI 0.22 to 9.82, very low quality evidence). All 10 participants allocated to benzodiazepines experienced any adverse event compared with 7/11 allocated to phenobarbital (RR 1.53, 95% CI 0.97 to 2.41, 1 RCT, 21 people, very low quality evidence). There was no clear difference in the incidence of participants leaving the study early for benzodiazepines compared with placebo (3 RCTs, 56 people, RR 2.73, 95% CI 0.15 to 48.04, very low quality evidence) or compared with phenobarbital (as active placebo) (no events, 1 RCT, 21 people, very low quality evidence). No trials reported on social confidence, social inclusion, social networks, or personalised quality of life, which are outcomes designated important by patients. No trials comparing benzodiazepines with placebo or treatment as usual reported on adverse effects.
AUTHORS' CONCLUSIONS
There is only evidence of very low quality from a few small and poorly reported trials on the effect of benzodiazepines as an adjunctive treatment for antipsychotic-induced TD. These inconclusive results mean routine clinical use is not indicated and these treatments remain experimental. New and better trials are indicated in this under-researched area; however, as benzodiazepines are addictive, we feel that other techniques or medications should be adequately evaluated before benzodiazepines are chosen.
Topics: Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Clonazepam; Dyskinesia, Drug-Induced; GABA Modulators; Humans; Phenobarbital; Randomized Controlled Trials as Topic
PubMed: 29352477
DOI: 10.1002/14651858.CD000205.pub3