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Journal of Parkinson's Disease 2023Balance impairment is a frequent cause of morbidity and mortality in people with Parkinson's disease (PD). As opposed to the effects of appendicular motor symptoms, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Balance impairment is a frequent cause of morbidity and mortality in people with Parkinson's disease (PD). As opposed to the effects of appendicular motor symptoms, the effects of Levodopa on balance impairment in idiopathic PD are less clear.
OBJECTIVE
To review the literature on the effects of oral Levodopa on clinical balance test performance, posturography, step initiation, and responses to perturbation in people with idiopathic PD (PwPD).
METHODS
A systematic search of three scientific databases (Pubmed, Embase, and Web of Science) was conducted in accordance with PRISMA guidelines. For the pilot meta-analysis, standardized mean differences with 95% confidence intervals were calculated using an inverse variance random effects model. Data not suitable for implementation in the meta-analysis (missing means or standard deviations, and non-independent outcomes) were analyzed narratively.
RESULTS
A total of 2772 unique studies were retrieved, of which 18 met the eligibility criteria and were analyzed, including data of 710 idiopathic PwPD. Levodopa had a significant positive effect on the Berg Balance Scale, the Push and Release test, and jerk and frequency parameters during posturography. In contrast, some significant negative effects on velocity-based sway parameters were found during posturography and step initiation. However, Levodopa had no significant effect on most step initiation- and all perturbation parameters.
CONCLUSION
The effects of Levodopa on balance in PwPD vary depending on the outcome parameters and patient inclusion criteria. A systematic approach with well-defined outcome parameters, and prespecified, sensitive and reliable tests is needed in future studies to unravel the effects of oral Levodopa on balance.
Topics: Humans; Levodopa; Parkinson Disease; Antiparkinson Agents; Postural Balance; Cognition
PubMed: 36617752
DOI: 10.3233/JPD-223536 -
Asian Journal of Psychiatry Jan 2023To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for... (Meta-Analysis)
Meta-Analysis
Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment.
OBJECTIVE
To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).
METHODS
Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.
RESULTS
We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).
CONCLUSION
Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).
Topics: Humans; Clozapine; Network Meta-Analysis; Entropy; Memantine; Mirtazapine; Antipsychotic Agents; Schizophrenia
PubMed: 36470132
DOI: 10.1016/j.ajp.2022.103375 -
Pituitary Feb 2023This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared...
PURPOSE
This systematic literature review investigated whether extended dosing intervals (EDIs) of pharmacological acromegaly treatments reduce patient burden and costs compared with standard dosing, while maintaining effectiveness.
METHODS
MEDLINE/Embase/the Cochrane Library (2001-June 2021) and key congresses (2018-2021) were searched and identified systematic literature review bibliographies reviewed. Included publications reported on efficacy/effectiveness, safety and tolerability, health-related quality of life (HRQoL), and patient-reported and economic outcomes in longitudinal/cross-sectional studies in adults with acromegaly. Interventions included EDIs of pegvisomant, cabergoline, and somatostatin receptor ligands (SRLs): lanreotide autogel/depot (LAN), octreotide long-acting release (OCT), pasireotide long-acting release (PAS), and oral octreotide; no comparator was required.
RESULTS
In total, 35 publications reported on 27 studies: 3 pegvisomant monotherapy, 11 pegvisomant combination therapy with SRLs, 9 LAN, and 4 OCT; no studies reported on cabergoline, PAS, or oral octreotide at EDIs. Maintenance of normal insulin-like growth factor I (IGF-I) was observed in ≥ 70% of patients with LAN (1 study), OCT (1 study), and pegvisomant monotherapy (1 study). Achievement of normal IGF-I was observed in ≥ 70% of patients with LAN (3 studies) and pegvisomant in combination with SRLs (4 studies). Safety profiles were similar across EDI and standard regimens. Patients preferred and were satisfied with EDIs. HRQoL was maintained and cost savings were provided with EDIs versus standard regimens.
CONCLUSIONS
Clinical efficacy/effectiveness, safety, and HRQoL outcomes in adults with acromegaly were similar and costs lower with EDIs versus standard regimens. Physicians may consider acromegaly treatment at EDIs, especially for patients with good disease control.
Topics: Adult; Humans; Acromegaly; Octreotide; Insulin-Like Growth Factor I; Cabergoline; Cross-Sectional Studies; Quality of Life; Peptides, Cyclic; Human Growth Hormone
PubMed: 36447058
DOI: 10.1007/s11102-022-01285-1 -
International Journal of Molecular... Nov 2022Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory... (Review)
Review
Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory infection. This narrative overview aims to summarise and discuss current knowledge and previous evidence regarding triggers and pathophysiology of GBS. A systematic search of the literature was carried out using suitable search terms. The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in three quarters of cases, are previous infections. The most common infectious agents that cause GBS include , , and cytomegalovirus. is responsible for about a third of GBS cases. GBS due to is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signalling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space. In conclusion, GBS is a neuro-immunological disorder caused by autoantibodies against components of the myelin sheath or axolemma. Molecular mimicry between surface structures of pathogens and components of myelin or the axon is one scenario that may explain the pathophysiology of GBS.
Topics: Humans; Amantadine; Autoantibodies; Axons; Campylobacter jejuni; Guillain-Barre Syndrome
PubMed: 36430700
DOI: 10.3390/ijms232214222 -
The Cochrane Database of Systematic... Nov 2022Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of... (Review)
Review
BACKGROUND
Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.
SEARCH METHODS
For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022.
SELECTION CRITERIA
We included randomised controlled (RCTs) trials that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled.
MAIN RESULTS
Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated "prevention" of cognitive problems (during radiotherapy and follow-up) and four studies investigated "amelioration" (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the "early radiotherapy treatment phase" were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the "early radiotherapy treatment phase" included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme. In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The "amelioration" pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had "stable" brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias.
AUTHORS' CONCLUSIONS
In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.
Topics: Adult; Humans; Modafinil; Donepezil; Memantine; Quality of Life; Cognitive Dysfunction; Cranial Irradiation; Cognition; Methylphenidate; Brain Neoplasms; Fatigue; Dementia
PubMed: 36427235
DOI: 10.1002/14651858.CD011335.pub3 -
CNS Drugs Dec 2022Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced... (Meta-Analysis)
Meta-Analysis
Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.
INTRODUCTION
Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD.
METHODS
A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness.
RESULTS
A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL.
CONCLUSIONS
This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
Topics: Humans; Middle Aged; Aged; Carbidopa; Levodopa; Quality of Life; Network Meta-Analysis; Parkinson Disease; Apomorphine
PubMed: 36414908
DOI: 10.1007/s40263-022-00963-9 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD)...
BACKGROUND
Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD) includes mild cognitive impairment (MCI) due to AD and mild AD dementia.
OBJECTIVE
The aim of this study was to investigate symptomatic treatment prevalence and treatment patterns in eAD.
METHODS
Embase, MEDLINE, and EBM Reviews were searched in November 2021 for observational studies reporting symptomatic treatment patterns in eAD. The range of patients receiving treatment was collated. Risk of bias was assessed using the Joanna Briggs Institute (JBI) prevalence tool. Two independent reviewers screened the records, one performed data extraction and quality assessment while a second checked.
RESULTS
Twenty-one studies (prospective and retrospective cohorts, cross-sectional studies, and a survey) were included. Population size ranged from 23 to 2,028. Worldwide, 18 to 35% of patients diagnosed with MCI due to AD received any AChE inhibitor (three studies; n = 631), 7 to 8% memantine (two studies; n = 229), and 9% combination therapy (one study; n = 402). Patients receiving no treatment ranged from 41 to 54% (two studies; n = 733). Worldwide, in mild AD dementia patients, 13 to 89% received any AChE inhibitor (six studies; n = 3,715), 1 to 21% memantine (five studies, n = 3,527), and 0.4 to 39% combination therapy (four studies, n = 3,018). Patients receiving no treatment ranged from 9 to 26% (five studies, n = 4,073).
CONCLUSION
Limitations in reporting led to unclear risk of bias. The results reveal a pattern of use of symptomatic treatment in eAD beyond approved labels and highlights the opportunity for new consensus guidelines to inform clinical practice.
Topics: Humans; Alzheimer Disease; Memantine; Prospective Studies; Cross-Sectional Studies; Retrospective Studies; Dementia; Cognitive Dysfunction; Disease Progression
PubMed: 36404542
DOI: 10.3233/JAD-220471 -
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 -
Neuromodulation : Journal of the... Feb 2023Subthalamic nucleus deep brain stimulation (DBS) is the most common therapeutic surgical procedure for patients with Parkinson's disease with motor fluctuations,...
BACKGROUND AND OBJECTIVES
Subthalamic nucleus deep brain stimulation (DBS) is the most common therapeutic surgical procedure for patients with Parkinson's disease with motor fluctuations, dyskinesia, or tremor. Routine follow-up of patients allows clinicians to anticipate replacement of the DBS battery reaching the end of its life. Patients who experience a sudden stop of the DBS battery experience a rapid worsening of symptoms unresponsive to high dose of levodopa, in a life-threatening phenomenon called "DBS-withdrawal syndrome." In the current context of the COVID-19 pandemic, in which many surgeries are being deprogrammed, it is of utmost importance to determine to what extent DBS battery replacement surgeries should be considered an emergency. In this study, we attempt to identify risk factors of DBS-withdrawal syndrome and provide new insights about pathophysiological hypotheses. We then elaborate on the optimal approach to avoid and manage such a situation.
MATERIALS AND METHODS
We conducted a systematic review of the literature on the subject and reported the cases of 20 patients (including five from our experience) with DBS-withdrawal syndrome, comparing them with 15 undisturbed patients (including three from our experience), all having undergone neurostimulation discontinuation.
RESULTS
A long disease duration at battery removal and many years of DBS therapy are the main potential identified risk factors (p < 0.005). In addition, a trend for older age at the event and higher Unified Parkinson's Disease Rating Scale motor score before initial DBS implantation (evaluated in OFF-drug condition) was found (p < 0.05). We discuss several hypotheses that might explain this phenomenon, including discontinued functioning of the thalamic-basal ganglia loop due to DBS-stimulation cessation in a context in which cortical-basal ganglia loop had lost its cortical input, and possible onset of a severe bradykinesia through the simultaneous occurrence of an alpha and high-beta synchronized state.
CONCLUSIONS
The patients' clinical condition may deteriorate rapidly, be unresponsive to high dose of levodopa, and become life-threatening. Hospitalization is suggested for clinical monitoring. In the context of the current COVID-19 pandemic, it is important to widely communicate the replacement of DBS batteries reaching the end of their life. More importantly, in cases in which the battery has stopped, there should be no delay in performing replacement as an emergent surgery.
Topics: Humans; Parkinson Disease; Levodopa; Deep Brain Stimulation; Pandemics; Treatment Outcome; COVID-19
PubMed: 36344398
DOI: 10.1016/j.neurom.2022.09.008 -
Journal of Enzyme Inhibition and... Dec 2023An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation...
An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity.
Topics: Antioxidants; Glycation End Products, Advanced; Molecular Docking Simulation; Serum Albumin, Bovine; Amantadine
PubMed: 36325591
DOI: 10.1080/14756366.2022.2137161