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Journal of Clinical Medicine Jul 2020Interest in an aetiopathogenic role for in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively.... (Review)
Review
Interest in an aetiopathogenic role for in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively. This systematic review, using an EMBASE database search, addresses Oxford Centre for Evidence-Based Medicine based questions on the inter-relationship of and IP, the benefits of eradicating in IP and the outcome of not treating. The search strategy was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines: 21 of 204 articles met the inclusion criteria. The results show that the assumption that any benefit of eradication results from improved levodopa bioavailability is unjustified. The inter-relationship between and IP is well-established. virulence markers (associated with autoimmunity and immune tolerance) influence the risk, severity and progression of IP. The birth cohort effect for virulence marker antibodies, seen in controls, is obliterated in IP, suggesting causality. Successful eradication in IP is disease-modifying (even in anti-parkinsonian treatment-naïve patients) but not preventive. Hypokinesia regresses with eradication and overall motor severity lessens. Eradication may influence gastrointestinal microbiota adversely, unlocking the next stage in the natural history, the development of rigidity. Failed eradication worsens hypokinesia, as does the presence/persistence of at molecular level only. Adequate prognostic assessment of the consequences of not treating , for IP, is prevented by a short follow-up. We conclude that is a pathophysiological driver of IP.
PubMed: 32650535
DOI: 10.3390/jcm9072159 -
Clinical Endocrinology Oct 2021The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both... (Meta-Analysis)
Meta-Analysis
PURPOSE
The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both Ga-DOTA peptides and F-fluorodihydroxyphenyl- l-alanine ( F-DOPA) PET/computed tomography (CT). As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data.
METHODS
PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of Ga-DOTA peptides and F-DOPA PET/CT; papers up to February 2021 were considered. In each study, we considered sensitivity in terms of patient-based analysis (PBA), region-based analysis (RBA) and lesion-based analysis (LBA), and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth.
RESULTS
Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NETs patients were included. The pooled sensitivity of F-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. Ga-DOTA peptides PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of F-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of F-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found; however, no publication bias was observed.
CONCLUSION
Both F-DOPA PET/CT and Ga-DOTA-peptides PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of F-DOPA PET/CT was observed. Thus, the use of F-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs.
Topics: Dihydroxyphenylalanine; Humans; Neuroendocrine Tumors; Organometallic Compounds; Peptides; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography
PubMed: 34018606
DOI: 10.1111/cen.14527 -
Endocrine Sep 2015Computed tomography (CT) and magnetic resonance imaging (MRI) are the major imaging modalities used for the localization of catecholamine-producing tumors... (Review)
Review
Computed tomography (CT) and magnetic resonance imaging (MRI) are the major imaging modalities used for the localization of catecholamine-producing tumors (pheochromocytoma and paraganglioma). Functional imaging (FI) offers an alternative approach to localize, evaluate, and stage these tumors. Our objective was to describe the additive benefit of FI studies for patients with pheochromocytoma and paraganglioma (PPG) who have undergone MRI or CT scan evaluation. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from database inception through June 2012 for studies that included patients with biochemically proven PPGs who underwent CT or MRI and additional FI for the localization of PPGs. We included 32 studies enrolling a total of 1,264 patients with a mean age of 43-years old. The studies were uncontrolled and evaluated six FI modalities. FI tests provided small additive value to CT/MRI, aiding in the localization of only 24/1,445 primary cases (1.4 %) and 28/805 metastatic cases (3.5 %). In metastatic cases, 6-[F-18]fluoro-L-dihydroxyphenylalanine (DOPA) and fluorodopamine-PET (FDA) were the FI tests most successful at identifying disease missed by CT/MRI, providing additional benefit in 6/60 (10 %) and 5/78 (6.4 %) cases, respectively. No clinically significant findings were observed in any of the predefined subgroups. No study evaluated the impact of FI on the completeness of surgical resection or other patient-important outcomes. Observational evidence suggests that FI tests have a limited additional role in patients with PPGs who have undergone CT/MRI evaluation. However, the role of FI tests in specific subgroups of patients with atypical presentations (metastatic, extra-adrenal) as well as the use of hybrid FI tests should be explored. Further research should also evaluate the impact of FI tests on patient-important outcomes.
Topics: Adrenal Gland Neoplasms; Adult; Humans; Middle Aged; Paraganglioma; Pheochromocytoma; Radionuclide Imaging
PubMed: 25663601
DOI: 10.1007/s12020-015-0544-7 -
Journal of Neurology Apr 2022The best choice between levodopa alone and levodopa sparing medications for early Parkinson's disease (PD) remains controversial. We aimed to evaluate the effect and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The best choice between levodopa alone and levodopa sparing medications for early Parkinson's disease (PD) remains controversial. We aimed to evaluate the effect and safety of levodopa alone and levodopa sparing therapy in symptom relief, neuroimage results and complications.
METHODS
A systematic search was performed in PubMed, The Cochrane Library, EMBASE, and Web of Science for randomized controlled trials of early PD patients comparing levodopa-alone with levodopa-sparing therapy. The mean difference (MD) and the risk ratio (RR) were meta-analyzed.
RESULTS
Twenty-three articles with 4913 patients were included. Significantly greater benefit was detected for the levodopa group in the changes of Unified Parkinson's Disease Rating Scale part II (p < 0.00001), III (p < 0.00001), and total (p < 0.00001) scores, and the between-group MD in part III score increased over time. The loss of the radioligands uptake in levodopa-alone group was also increasingly greater over time. Patients treated with levodopa alone were at higher risk for wearing-off (p < 0.001) and dyskinesia (p < 0.001), but the RR for dyskinesia between the two groups decreased after 2 years of follow-up.
CONCLUSION
Levodopa-alone therapy might be superior in motor symptom relief than levodopa-sparing therapy for early PD patients, and the motor advantage of levodopa-alone might grow over time. Sparing therapy might be associated with less risk of wearing-off and dyskinesia, but the events between the two groups might not be different in the long run. Overall, levodopa alone therapy might bring more net benefit to early PD patients compared with levodopa sparing strategies. The clinical and imaging findings are conflicting, which requires further investigation.
Topics: Antiparkinson Agents; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease
PubMed: 34652505
DOI: 10.1007/s00415-021-10830-0 -
Cureus Mar 2023Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This... (Review)
Review
Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This disease is difficult to diagnose since its symptoms are similar to those of the aging process. Those with PD have impaired motor control and function, dyskinesia, and tremors. To treat PD, drugs that enhance the amount of dopamine given to the brain are administered to alleviate symptoms. This inquiry examines the prescription of rotigotine to achieve this objective. The primary objective of this review is to examine the usage of rotigotine in both the late and early stages of PD. The statistical model utilized in the review found that there was not a significant difference in the dosage of rotigotine prescribed to late and early-stage PD patients, however, there were some confounding variables that may have skewed this result; therefore, further research is necessary to validate or nullify this hypothesis.
PubMed: 37069881
DOI: 10.7759/cureus.36211 -
Archives of Gerontology and Geriatrics 2021To identify drug interactions of potentially inappropriate medications and mental and behavioral disorders, according to explicit potentially inappropriate medications... (Review)
Review
OBJECTIVES
To identify drug interactions of potentially inappropriate medications and mental and behavioral disorders, according to explicit potentially inappropriate medications criteria-based tools.
METHODOLOGY
A systematic scoping review was conducted in February 2020. Study characteristics, potentially inappropriate medications, drug interactions, rationale, and therapeutic management proposed were extracted. The commercialization and potentially inappropriate medications standard as essential in Brazil and in the world were identified. Therapeutic management was proposed for the most cited potentially inappropriate medications.
RESULTS
36 tools including 151 drug interactions, in addition to 132 potentially inappropriate medications with concerns related to six mental and behavioral disorders were identified. Cognitive impairment and dementia were the most frequently disorders reported and antipsychotics, anticholinergics, and benzodiazepines were the pharmacological classes more involved in the drug interactions. Despite the tools recommended risperidone and quetiapine when the use of antipsychotics were inevitable; levodopa + carbidopa for Parkinson's disease; and short and intermediate half-life benzodiazepines; the quality of the evidence needs to be assessed. In this review, sleep hygiene; deprescription; medication review; and clinical monitoring of adverse drug reactions are strongly recommended. In addition, to consider agomelatine, bupropion, moclobemide and melatonin as potential safer options for benzodiazepines.
CONCLUSION
Knowing the clinical conditions or risk morbidities associated with the use of potentially inappropriate medications and management of these medications for safer therapeutic equivalents or non-pharmacotherapeutic alternatives are relevant for patient safety.
Topics: Aged; Brazil; Drug Interactions; Humans; Inappropriate Prescribing; Mental Disorders; Potentially Inappropriate Medication List
PubMed: 33227533
DOI: 10.1016/j.archger.2020.104283 -
Expert Review of Pharmacoeconomics &... 2016Parkinson's disease (PD) is the second most common neurodegenerative disease. There are no clinical trials comparing all available pharmacological therapies for the... (Comparative Study)
Comparative Study Review
Parkinson's disease (PD) is the second most common neurodegenerative disease. There are no clinical trials comparing all available pharmacological therapies for the treatment of early PD. The objective of this review is to indirectly analyze the efficacy of antiparkinson drugs currently available in Latin America. A systematic review was performed exploring only placebo-controlled randomized trials comparing antiparkinson monotherapy (levodopa, pramipexole, rasagiline, or selegiline) in patients with PD on Hoehn and Yahr stages I through III published from January 1994 to May 2014. The primary outcome was the mean change in the Unified PD Rating Scale (UPDRS) I, II and III. A mixed treatment comparison analysis (indirect comparisons) through a random-effects model was performed. Levodopa demonstrated the highest effects in terms of UPDRS score improvement both from baseline and when compared to other treatments. Levodopa showed a 60.1% probability of granting the greatest reduction in UPDRS I, II and III.
Topics: Antiparkinson Agents; Drug Therapy, Combination; Humans; Latin America; Models, Statistical; Parkinson Disease; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26731410
DOI: 10.1586/14737167.2016.1135740 -
CNS Drugs May 2016Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor... (Review)
Review
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) is available in several countries for the treatment of advanced levodopa-responsive Parkinson's disease (PD) with severe motor fluctuations and dyskinesia when other treatments have not given satisfactory results.
OBJECTIVE
Our objective was to summarize the present evidence base for LCIG therapy through a systematic review of the literature.
METHODS
Studies were identified from the PubMed and EMBASE databases up to 12 March 2016 using the following search terms: Parkinson disease, duodopa, levodopa/carbidopa intestinal gel, levodopa-carbidopa intestinal gel, LCIG, l-dopa infusion, levodopa infusion, duodenal l-dopa infusion, and duodenal levodopa infusion. Data extraction focused on whether LCIG therapy improves motor and non-motor outcomes as well as quality of life in PD patients compared with conventional therapy, apomorphine infusion, or deep brain stimulation. Randomized controlled trials (RCTs) and observational studies, with or without a control group, that included more than ten patients were included. The search was limited to peer-reviewed articles published in full in the English language and involving humans.
RESULTS
Infusion of LCIG reduced "off" time, increased "on" time without increasing troublesome dyskinesias, and improved quality of life in three RCTs (one double-blind). Open-label follow-ups confirm these findings. The data evaluating long-term efficacy and safety are still limited.
CONCLUSIONS
The quality of evidence that LCIG is effective in reducing fluctuating motor symptoms and improving quality of life is moderate. Quality of evidence for reduction of non-motor symptoms is very low. Safety issues mainly relate to the intestinal infusion system. LCIG might be a useful treatment option in PD patients with severe motor fluctuations.
Topics: Antiparkinson Agents; Carbidopa; Drug Combinations; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 27138916
DOI: 10.1007/s40263-016-0336-5 -
General Hospital Psychiatry 2022The present study aimed to systematically analyze the risk factors for RBD. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The present study aimed to systematically analyze the risk factors for RBD.
METHODS
A systematic review and meta-analysis of case-control studies, cohort studies, and cross-sectional studies derived from the articles published in eight electronic databases before December 1, 2021. The primary outcome was the odds ratio (OR) and 95% confidence interval (95% CI), and heterogeneity was quantified using I. Subgroup analyses and meta-regression were used to explore sources of heterogeneity. Egger's test and sensitivity analysis were performed. The PROSPERO ID number of the present study is CRD42021293942.
RESULTS
We identified 26 studies (44,230 subjects) among 2022 citations, and 13 factors were considered. Male sex (OR = 1.36, 95% CI = 1.13-1.64), smoking (OR = 1.37, 95% CI: 1.26-1.50), depression (OR = 2.06, 95% CI = 1.66-2.56), antidepressant use (OR = 2.36, 95% CI = 1.98-2.82), duration of neuropsychiatric disorders(OR = 1.43, 95% CI = 1.13-1.73), levodopa equivalent daily dose (LEDD, OR = 60.15, 95% CI = 23.95-96.35) and observable motor dysfunction (OR = 2.43, 95% CI = 0.65-4.22) were associated with a higher risk of RBD. Tertiary education and above (OR = 0.58, 95% CI = 0.35-0.96) was associated with a lower RBD risk. Men (OR = 1.40, 95% CI: 1.10-1.78, I = 0%, P = 0.005) and older individual (OR = 2.73, 95% CI: 1.03-4.43, I = 60%, P = 0.002) were more likely to have iRBD.
CONCLUSION
Six modifiable risk factors and one protective factor were associated with RBD. Further research is required to understand the mechanisms and to develop preventative strategies.
Topics: Male; Humans; Cross-Sectional Studies; REM Sleep Behavior Disorder; Levodopa; Risk Factors; Sleep
PubMed: 36375340
DOI: 10.1016/j.genhosppsych.2022.10.009 -
Journal of Clinical Sleep Medicine :... Apr 2023Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for... (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
Periodic limb movements during sleep (PLMS) are a frequent finding in restless legs syndrome, but their impact on sleep is still debated, as well the indication for treatment. We systematically reviewed the available literature to describe which drug categories are effective in suppressing PLMS, assessing their efficacy through a meta-analysis, when this was possible.
METHODS
The review protocol was preregistered on PROSPERO (CRD42021175848), and the systematic search was conducted on and EMBASE (last searched on March 2020). We included original human studies, which assessed PLMS modification on drug treatment with a full-night polysomnography, through surface electrodes on each tibialis anterior muscle. When at least 4 studies were available on the same drug or drug category, we performed a random-effect model meta-analysis.
RESULTS
Dopamine agonists like pramipexole and ropinirole resulted the most effective, followed by l-dopa and other dopamine agonists. Alpha2delta ligands are moderately effective as well opioids, despite available data on these drugs are much more limited than those on dopaminergic agents. Valproate and carbamazepine did not show a significant effect on PLMS. Clonazepam showed contradictory results. Perampanel and dypiridamole showed promising but still insufficient data. The same applies to iron supplementation.
CONCLUSIONS
Dopaminergic agents are the most powerful suppressors of PLMS. However, most therapeutic trials in restless legs syndrome do not report objective polysomnographic findings, there is a lack of uniformity in presenting results on PLMS. Longitudinal polysomnographic interventional studies, using well-defined and unanimous scoring criteria and endpoints on PLMS are needed.
CITATION
Riccardi S, Ferri R, Garbazza C, Miano S, Manconi M. Pharmacological responsiveness of periodic limb movements in patients with restless legs syndrome: a systematic review and meta-analysis. . 2023;19(4):811-822.
Topics: Humans; Restless Legs Syndrome; Dopamine Agonists; Nocturnal Myoclonus Syndrome; Movement; Dopamine Agents
PubMed: 36692194
DOI: 10.5664/jcsm.10440