scholarly journals Cerebrospinal fluid biomarkers for the diagnosis and prognosis of Parkinson’s disease: protocol for a systematic review and individual participant data meta-analysis

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e018177 ◽  
Author(s):  
Paolo Eusebi ◽  
Oskar Hansson ◽  
Silvia Paciotti ◽  
Massimiliano Orso ◽  
Davide Chiasserini ◽  
...  

IntroductionIdiopathic Parkinson’s disease (PD) is a progressive neurodegenerative disorder related to α-synuclein misfolding and aggregation. For this reason, it belongs to the family of ‘synucleinopathies’, which also includes some other neurological diseases. Although imaging and ancillary investigations may be helpful in the diagnostic workup, the diagnosis of PD mostly relies on the clinician’s expertise. Furthermore, there is a need today for markers that can track the disease progression in PD that might improve the evaluation of novel disease-modifying therapies. The cerebrospinal fluid (CSF) has been widely investigated with the purpose of finding useful diagnostic and prognostic biomarkers for PD.Methods and analysisThis systematic review protocol has been developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol 2015 statement and was registered on the PROSPERO international prospective register of systematic reviews. An international collaboration will be established. We will search the Cochrane Library, Web of Science, Medline and Embase from inception, using appropriate search strategies. Individual participant data from all included studies will be merged into a single database. We will include any study assessing the diagnostic and prognostic role of CSF biomarkers in PD. To evaluate the risk of bias and applicability of primary diagnostic accuracy studies, we will use Quality Assessment of Diagnostic Accuracy Studies-2 and Quality in Prognostic Studies. We will use standard meta-analytic procedures. We will first explore the utility of each CSF biomarker in turn. For each biomarker, we will assess its diagnostic and prognostic utility by means of receiver operating characteristic analysis and regression models. We will then move towards a multivariate approach considering different panels of biomarkers.Ethics and disseminationOur study will not include confidential data, and no intervention will be involved, so ethical approval is not required. The results of the study will be reported in international peer-reviewed journals.

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e026598 ◽  
Author(s):  
Andrea Benedetti ◽  
Yin Wu ◽  
Brooke Levis ◽  
Machelle Wilchesky ◽  
Jill Boruff ◽  
...  

IntroductionThe 30-item Geriatric Depression Scale (GDS-30) and the shorter GDS-15, GDS-5 and GDS-4 are recommended as depression screening tools for elderly individuals. Existing meta-analyses on the diagnostic accuracy of the GDS have not been able to conduct subgroup analyses, have included patients already identified as depressed who would not be screened in practice and have not accounted for possible bias due to selective reporting of results from only better-performing cut-offs in primary studies. Individual participant data meta-analysis (IPDMA), which involves a standard systematic review, then a synthesis of individual participant data, rather than summary results, could address these limitations. The objective of our IPDMA is to generate accuracy estimates to detect major depression for all possible cut-offs of each version of the GDS among studies using different reference standards, separately and among participant subgroups based on age, sex, dementia diagnosis and care settings. In addition, we will use a modelling approach to generate individual participant probabilities for major depression based on GDS scores (rather than a dichotomous cut-off) and participant characteristics (eg, sex, age, dementia status, care setting).Methods and analysisIndividual participant data comparing GDS scores to a major depression diagnosis based on a validated structured or semistructured diagnostic interview will be sought via a systematic review. Data sources will include Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO and Web of Science. Bivariate random-effects models will be used to estimate diagnostic accuracy parameters for each cut-off of the different versions of the GDS. Prespecified subgroup analyses will be conducted. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.Ethics and disseminationThe findings of this study will be of interest to stakeholders involved in research, clinical practice and policy.PROSPERO registration numberCRD42018104329.


2020 ◽  
Vol 34 (11) ◽  
pp. 1355-1367
Author(s):  
Zhenlan Li ◽  
Tian Wang ◽  
Haoyang Liu ◽  
Yan Jiang ◽  
Zhen Wang ◽  
...  

Objective: The aim of the present study was to systematically evaluate and quantify the effectiveness of dual-task training on gait parameters, motor symptoms and balance in individuals diagnosed with Parkinson’s disease. Data resources: A systematic review of published literature was conducted until May 2020, using PubMed, EMBASE, Cochrane Library, Web of Science, EBSCO and CNKI databases. Methods: We included randomized controlled trials (RCTs) and non-RCTs to evaluate the effects of dual-task training compared with those of non-intervention or other forms of training. The measurements included gait parameters, motor symptoms and balance parameters. Methodological quality was assessed using the PEDro scale. Outcomes were pooled by calculating between-group mean differences using fixed- or random-effects models based on study heterogeneity. Results: A total of 11 RCTs comprising 322 subjects were included in the present meta-analysis. Results showed that dual-task training significantly improved gait speed (standardized mean difference [SMD], −0.23; 95% confidence interval [CI], −0.38 to −0.08; P = 0.002), cadence (SMD, −0.25; 95% CI, −0.48 to −0.02; P = 0.03), motor symptoms (SMD, 0.56; 95% CI, 0.18 to 0.94; P = 0.004) and balance (SMD, −0.44; 95% CI, −0.84 to −0.05; P = 0.03). However, no significant changes were detected in step length or stride length. Conclusion: Dual-task training was effective in improving gait performance, motor symptoms and balance in patients with Parkinson’s disease relative to other forms of training or non-intervention.


2016 ◽  
Vol 135 (1) ◽  
pp. 34-56 ◽  
Author(s):  
A. D. Andersen ◽  
M. Binzer ◽  
E. Stenager ◽  
J. B. Gramsbergen

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiaopeng Wen ◽  
Kunbin Li ◽  
Hao Wen ◽  
Qian Wang ◽  
Zhiyuan Wu ◽  
...  

Objective: This systematic review and meta-analysis aimed to assess the effects of the combination of acupuncture-related therapies with conventional medication compared with conventional medication in patients with Parkinson's disease (PD).Methods: A literature search within eight databases [including Medline, Embase, the Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang Database] was performed covering a time frame from their inception to August 2020. Randomized controlled trials (RCTs) comparing acupuncture-related therapies combined with conventional medication vs. conventional medication in patients with PD were eligible. Two authors independently assessed the risk of bias. Assessments were performed with the total and subscales scores of the Unified Parkinson's Disease Rating Scale (UPDRS), 39-item Parkinson's Disease Questionnaire (PDQ-39), the dosage of Madopar, Mini-Mental State Examination (MMSE), and 17-item Hamilton Depression Scale (HAMD). Data were analyzed by adopting the Cochrane Collaboration's RevMan 5.4 (Review Man, Copenhagen, Denmark); and mean effect sizes and 95% confidence intervals were estimated. Tests for heterogeneity were used to assess differences in treatment effects across different types of acupuncture used.Results: Sixty-six trials met the inclusion criteria, of which 61 trials provided data for the meta-analysis. We defined high-quality articles as those with a low risk of bias in four or more domains; and only 10 (15.15%) articles were of high quality. Compared with the controls, acupuncture-related therapies with conventional medication achieved a benefit in the primary outcomes of UPDRS (motor subscore: −3.90, −4.33 to −3.49, P < 0.01; total score: −7.37 points, −8.91 to −5.82, P < 0.001; activities of daily living subscore: −3.96, −4.96 to −2.95, P < 0.01). For the subgroup difference test among the effects of different acupuncture methods, significant differences existed in outcomes with the UPDRS-III, UPDRS-I, UPDRS-IV, and PDQ-39 scores and Madopar dosage, while non-significant differences existed with the UPDRS-total, UPDRS-II, HAMD, and MMSE scores.Conclusions: Acupuncture-related therapies combined with conventional medication may benefit individuals with PD. Our review findings should be considered with caution because of the methodological weaknesses in the included trials. Future, large randomized trials of acupuncture-related therapies for PD with high methodological quality are warranted.Systematic Review Registration: Identifier CRD42021228110.


2021 ◽  
Vol 12 ◽  
Author(s):  
XinYue Zhang ◽  
Zhen Svn ◽  
MengSi Liv ◽  
Yan Yang ◽  
Rui Zeng ◽  
...  

Background: Parkinson's disease (PD) and irritable bowel syndrome (IBS) are respectively one of the most common neurodegenerative diseases and functional bowel diseases in the world. Recent studies suggest that patients with IBS seem to have a higher risk of PD, which conflicts with the result of previous meta-analysis. Therefore, the purpose of this systematic review is to evaluate all available evidence, in order to clarify the association between PD and IBS.Methods: Two reviewers independently searched the PubMed, Embase, Web of Science, and Cochrane library on April 25, 2021 to identify all records that explore the association between IBS and PD. All reports that clearly define PD and IBS and analyze the relationship between the two were included. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies.Results: Five studies from four articles involving 2,044,110 subjects were included in this analysis. The pooled results demonstrated a significant association between PD and IBS (1.48; 95% CI: 1.35–1.62, P < 0.001), with subtle heterogeneity (I2 = 0.0%, p = 0.585). The association was observed across genders and increased with age. However, the available evidence cannot allow a reliable analysis of the causal relationship between IBS and PD.Conclusion: This study demonstrates a higher risk of PD among subjects with IBS. Future studies are required to further clarify the causation and underlying mechanism of the association.


2021 ◽  
Vol 13 ◽  
Author(s):  
Xiang Liu ◽  
Huiyu Liu ◽  
Zicai Liu ◽  
Jinzhu Rao ◽  
Jing Wang ◽  
...  

Background: Parkinson's disease is a common neurodegenerative disorder with motor and non-motor symptoms. Recently, as adjuvant therapy, transcranial direct current stimulation (tDCS) has been shown to improve the motor and non-motor function of patients with Parkinson's disease (PD). This systematic review aimed to evaluate the existing evidence for the efficacy of tDCS for PD. We included English databases (PubMed, the Cochrane Library, Embase, and Web of Science) and Chinese databases [Wanfang database, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and China Biology Medicine (CBM)] without restricting the year of publication. Twenty-one tDCS studies, with a total of 736 participants, were included in the analysis. Two independent researchers extracted the data and characteristics of each study. There was a significant pooled effect size (−1.29; 95% CI = −1.60, −0.98; p < 0.00001; I2 = 0%) in the Unified PD Rating Scale (UPDRS) I and the Montreal cognitive assessment (SMD = 0.87, 95% CI = 0.50 to 1.24; p < 0.00001; I2 = 0%). The poor effect size was observed in the UPDRS III scores (SMD = −0.13; 95% CI = −0.64, 0.38; p = 0.61; I2 = 77%), and similar results were observed for the timed up and go (TUG) test, Berg balance scale, and gait assessment. The results of this meta-analysis showed that there was insufficient evidence that tDCS improves the motor function of patients with PD. However, tDCS seemed to improve their cognitive performance. Further multicenter research with a larger sample size is needed. In addition, future research should focus on determining the tDCS parameters that are most beneficial to the functional recovery of patients with PD.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tamara Chambers-Richards ◽  
Yingying Su ◽  
Batholomew Chireh ◽  
Carl D’Arcy

Abstract Objectives Earlier longitudinal reviews on environmental and occupational toxins and Parkinson’s disease (PD) risk have limitations. This study aimed to determine the strength of association between three types of toxic occupational exposures and the occurrence of PD by diagnostic methods. Methods A search was conducted of EMBASE, PubMed/Medline, Toxnet, LILACS, and Cochrane Library databases for longitudinal studies that assessed toxic occupational exposure, Parkinsonian, or related disorders, diagnosed by International Classification of Diseases (ICD) codes, medical records, or confirmation by a neurologist/nurse, and published in the English language from January 1990 to July 2021. Pooled risk ratios (RR) estimates were produced using random-effects models. Systematic review with meta-analysis synthesized the results. Study quality, heterogeneity, and publication bias were examined. High-quality articles that met the inclusion criteria were analyzed. Results Twenty-four articles were used in the analyses. The pooled RR for electromagnetic exposure and PD were (RR=1.03, 95% confidence interval [CI] 0.91–1.16) while the pooled RR between PD and metal and pesticide exposure were (RR=1.07, 95% CI 0.92–1.24) and (RR=1.41, 95% CI 1.20–1.65), respectively. Pooled RR for methods of diagnosis and their associations with PD were: confirmation by a neurologist or nurse (RR=2.17, 95% CI 1.32–3.54); ICD codes (RR=1.14, 95% CI 1.03–1.26), and medical records (RR=1.06, 95% CI 0.92–1.21). Conclusions Our systematic review provides robust evidence that toxic occupational exposures are significant risk factors for PD especially those diagnosed by neurologists or nurses using standardized methods.


Author(s):  
Veena Sheshadri ◽  
Nathan C. Rowland ◽  
Jigesh Mehta ◽  
Marina Englesakis ◽  
Pirjo Manninen ◽  
...  

AbstractBackground: Subthalamic nucleus deep brain stimulation (STN–DBS) has become a standard treatment for many patients with Parkinson’s disease (PD). The reported clinical outcome measures for procedures done under general anesthesia (GA) compared to traditional local anesthetic (LA) technique are quite heterogeneous and difficult to compare. The aim of this systematic review and metaanalysis was to determine whether the clinical outcome after STN–DBS insertion under GA is comparable to that under LA in patients with Parkinson’s disease. Methods: The databases of Medline Embase, Cochrane library and Pubmed were searched for eligible studies (human trials, English language, published between 1946 and January of 2016). The primary outcome of this study was to assess the postoperative improvement in the symptoms, evaluated using either Unified Parkinson’s Disease Rating Scale (UPDRS) scores or levodopa equivalent dosage (LEDD) requirement. Results: The literature searches yielded 395 citations and six retrospective cohort studies with a sample size of 455 (194 in GA and 261 in LA) were included in the analysis. Regarding the clinical outcomes, there were no significant differences in the postoperative Unified Parkinson’s disease rating scale and levodopa equivalent drug dosage between the GA and the LA groups. Similarly, the adverse events and target accuracy were also comparable between the groups. Conclusions: This systematic review and meta-analysis shows that currently there is no good quality data to suggest equivalence of GA to LA during STN-DBS insertion in patients with PD, with some factors trending towards LA. There is a need for a prospective randomized control trial to validate our results.


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