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American Journal of Respiratory and... Jun 2018This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD).
TARGET AUDIENCE
Clinicians investigating adult and pediatric patients for possible PCD.
METHODS
Systematic reviews and, when appropriate, meta-analyses were conducted to summarize all available evidence pertinent to our clinical questions. Evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for diagnosis and discussed by a multidisciplinary panel with expertise in PCD. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. Three conflicted individuals were also prohibited from writing, editing, or providing feedback on the relevant sections of the manuscript.
RESULTS
After considering diagnostic test accuracy, confidence in the estimates for each diagnostic test, relative importance of test results studied, desirable and undesirable direct consequences of each diagnostic test, downstream consequences of each diagnostic test result, patient values and preferences, costs, feasibility, acceptability, and implications for health equity, the panel made recommendations for or against the use of specific diagnostic tests as compared with using the current reference standard (transmission electron microscopy and/or genetic testing) for the diagnosis of PCD.
CONCLUSIONS
The panel formulated and provided a rationale for the direction as well as for the strength of each recommendation to establish the diagnosis of PCD.
Topics: Cilia; Cohort Studies; Cross-Sectional Studies; Diagnostic Techniques and Procedures; Genetic Predisposition to Disease; Humans; Kartagener Syndrome; Practice Guidelines as Topic; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Societies, Medical; United States
PubMed: 29905515
DOI: 10.1164/rccm.201805-0819ST -
BMJ Clinical Evidence Feb 2014Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or... (Review)
Review
INTRODUCTION
Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of Ashkenazi descent.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal and generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 19 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acupuncture, amantadine, baclofen, benzatropine, biofeedback, botulinum toxins, bromocriptine, carbamazepine, carbidopa/levodopa, clonazepam, clozapine, deep brain stimulation of thalamus and globus pallidus, diazepam, gabapentin, haloperidol, lorazepam, myectomy (for focal dystonia), occupational therapy, ondansetron, physiotherapy, pregabalin, procyclidine, selective peripheral denervation (for focal dystonia), speech therapy, tizanidine, trazodone hydrochloride, and trihexyphenidyl.
Topics: Analgesics; Anticonvulsants; Dystonia; Humans; Physical Therapy Modalities; Speech Therapy; Treatment Outcome
PubMed: 25347760
DOI: No ID Found -
BMJ Clinical Evidence Jun 2011Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or... (Review)
Review
INTRODUCTION
Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal, and for generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acetylcholine release inhibitors (botulinum toxin), acupuncture, anticholinergic/antihistaminic drugs, anticonvulsants, atypical antipsychotic drugs, benzodiazepines, biofeedback, chiropractic manipulation, deep brain stimulation of thalamus and globus pallidus, dopaminergic agonists and antagonists, gamma-aminobutyric acid (GABA) analogues, microvascular decompression, muscle relaxants, myectomy, occupational therapy, osteopathy, pallidotomy, physiotherapy, selective peripheral denervation, serotonergic agonists and antagonists, speech therapy, and thalamotomy.
Topics: Botulinum Toxins; Dystonia; Dystonia Musculorum Deformans; Dystonic Disorders; GABA Antagonists; Globus Pallidus; Humans
PubMed: 21663705
DOI: No ID Found -
Anaesthesia Mar 2019Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary... (Meta-Analysis)
Meta-Analysis
Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary aim of this review was to examine whether dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. We sought randomised clinical trials in MEDLINE, EMBASE, PubMed and CENTRAL from their inception until June 2018. Observational studies, case reports, case series and non-systematic reviews were excluded. Twenty-five trials including 3240 patients were eligible for inclusion in the data synthesis. In the patients who received dexmedetomidine (eight trials, 1425 patients), delirium was reduced, odds ratio (95%CI) 0.36 (0.26-0.51), p < 0.001 and high quality of evidence. The use of dexmedetomidine was associated with a reduced incidence of agitation, OR (95%CI) 0.34 (0.20-0.59), p < 0.001, moderate quality of evidence. Patients who were randomly assigned to dexmedetomidine had a significantly higher incidence of bradycardia, OR (95%CI) 2.18 (1.46-3.24), p < 0.001, moderate quality of evidence; and hypotension, OR (95%CI) 1.89 (1.48-2.41), p < 0.001, high quality of evidence. We found no evidence of an effect on mortality, OR (95%CI) 0.86 (0.66-1.10), p = 0.23, moderate quality of evidence. The trial sequential analyses for the incidence of delirium, bradycardia and hypotension was conclusive but not for the incidence of agitation and mortality. In summary, this meta-analysis suggests that dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. The general quality of evidence ranged from moderate to high.
Topics: Delirium; Dexmedetomidine; Humans; Intensive Care Units; Psychomotor Agitation
PubMed: 30367689
DOI: 10.1111/anae.14472 -
BMJ Open Jul 2019The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain...
OBJECTIVE
The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).
METHODS
We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.
RESULTS
Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.
CONCLUSIONS
Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.
PROSPERO REGISTRATION NUMBER
CRD42016033140.
Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Psychomotor Agitation; Psychoses, Substance-Induced; Randomized Controlled Trials as Topic
PubMed: 31289093
DOI: 10.1136/bmjopen-2019-029604 -
BMJ Clinical Evidence Sep 2008Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or... (Review)
Review
INTRODUCTION
Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal, and for generalised dystonia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 13 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acetylcholine receptor inhibitors, acupuncture, anticholinergic drugs, anticonvulsants, atypical antipsychotic drugs, benzodiazepines, biofeedback, botulinum toxin, chiropractic manipulation, deep brain stimulation of thalamus and globus pallidus, dopaminergic agonists and antagonists, gamma-aminobutyric acid (GABA) inhibitors, microvascular decompression, myectomy, occupational therapy, osteopathy, pallidotomy, physiotherapy, selective peripheral denervation, serotonergic agonists and antagonists, speech therapy, and thalamotomy.
Topics: Botulinum Toxins; Deep Brain Stimulation; Dystonia; Dystonia Musculorum Deformans; Dystonic Disorders; Follow-Up Studies; GABA Antagonists; Globus Pallidus; Humans
PubMed: 19445800
DOI: No ID Found -
Orphanet Journal of Rare Diseases Jul 2022Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic... (Review)
Review
BACKGROUND
Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic location and ethnic origin. However, data about Chinese patients are limited. We aimed to summarize the clinical and genetic spectrum of Chinese PCD patients based on all available literatures.
METHODS
We searched Embase, Pubmed, Web of Science and Chinese databases including CNKI, SinoMed and Wanfang from 1981 to 2021, to identify articles reporting patients with PCD in China, which had included information about transmission electron microscopy and/or genetic testing.
RESULTS
A total of 244 Chinese PCD patients in 52 articles were included. Of these patients, the mean age was 13.1 years, and 55 patients (22.5%) were diagnosed with PCD after 18 years old. Compared with patients diagnosed with PCD in childhood or infancy, patients diagnosed with PCD in adulthood had a higher prevalence of chronic wet cough, sinusitis, Pseudomonas aeruginosa (PA) isolation and radiological bronchiectasis as well as worse lung function. 25 PCD-related genes were identified in 142 patients, and DNAH5, DNAH11, CCDC39 and CCDC40 were the most frequently detected mutations. More than half of genetic variants were loss-of-function mutations, and the majority of these variants were seen only once. Correlations between PCD phenotype, genotype and ciliary ultrastructure were also evidenced.
CONCLUSIONS
Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome. Specialist equipment and expertise are urgently required to facilitate the early diagnosis and treatment of PCD.
TRIAL REGISTRY
PROSPERO; No.: CRD42021257804; URL: www.crd.york.ac.uk/prospero/.
Topics: Cilia; Ciliary Motility Disorders; Delayed Diagnosis; Genotype; Humans; Kartagener Syndrome; Mutation; Phenotype
PubMed: 35854386
DOI: 10.1186/s13023-022-02427-1 -
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 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Neurology May 2019To systematically evaluate the efficacy of treatments for tics and the risks associated with their use.
OBJECTIVE
To systematically evaluate the efficacy of treatments for tics and the risks associated with their use.
METHODS
This project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology's guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics.
RESULTS
There was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs.
CONCLUSIONS
There is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations.
Topics: Antipsychotic Agents; Behavior Therapy; Deep Brain Stimulation; Humans; Tic Disorders; Tics; Tourette Syndrome
PubMed: 31061209
DOI: 10.1212/WNL.0000000000007467