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Journal of Clinical Medicine Apr 2023Globally, stroke is the second leading cause of death and disability. In different studies conducted previously, the choline-containing phospholipids citicoline and... (Review)
Review
BACKGROUND
Globally, stroke is the second leading cause of death and disability. In different studies conducted previously, the choline-containing phospholipids citicoline and choline alphoscerate have been proposed as adjuvants in the treatment of acute strokes. A systematic review was conducted to provide updated information on the effects of citicoline and choline alphoscerate in patients with acute and hemorrhagic strokes.
METHODS
PubMed/Medline, Scopus, and Web of Science were searched to identify relevant materials. Data were pooled, and odds ratios (OR) were reported for binary outcomes. Using mean differences (MD), we evaluated continuous outcomes.
RESULTS
A total of 1460 studies were reviewed; 15 studies with 8357 subjects met the eligibility criteria and were included in the analysis. In our study, citicoline treatment did not result in improved neurological function (NIHSS < 1, OR = 1.05; 95% confidence interval (CI): 0.87-1.27) or functional recovery (mRS < 1, OR = 1.36; 95% CI: 0.99-1.87) in patients with acute stroke. Choline alphoscerate improved neurological function and functional recovery in stroke patients based on the Mathew's scale and the Mini-Mental State Examination (MMSE).
CONCLUSION
Citicoline did not improve the neurological or functional outcomes in acute stroke patients. In contrast, choline alphoscerate improved neurological function and functional recovery and reduced dependency in stroke patients.
PubMed: 37109211
DOI: 10.3390/jcm12082875 -
Journal of Alzheimer's Disease : JAD 2023Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function impairment occurring in neurological conditions including adult-onset dementia disorders. Despite its 1985 marketing authorization, there are still discrepancies between countries regarding its approval as a prescription medicine and discussions about its effectiveness.
OBJECTIVE
This study aimed to evaluate the efficacy of the α-GPC compound for treating cognitive impairment in patients with adult-onset neurological disorders.
METHODS
Relevant studies were identified by searching PubMed, Web of Science, and Embase. Studies that evaluated the effects of α-GPC alone or in combination with other compounds on adult-onset cognitive impairment reporting cognition, function, and behavior were considered. We assessed the risk of bias of selected studies using the Cochrane risk of bias tool.
RESULTS
A total of 1,326 studies and 300 full-text articles were screened. We included seven randomized controlled trials (RCTs) and one prospective cohort study that met our eligibility criteria. We found significant effects of α-GPC in combination with donepezil on cognition [4 RCTs, mean difference (MD):1.72, 95% confidence interval (CI): 0.20 to 3.25], functional outcomes [3 RCTs, MD:0.79, 95% CI: 0.34 to 1.23], and behavioral outcomes [4 RCTs; MD: -7.61, 95% CI: -10.31 to -4.91]. We also observed that patients who received α-GPC had significantly better cognition than those who received either placebo or other medications [MD: 3.50, 95% CI: 0.36 to 6.63].
CONCLUSION
α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.
Topics: Humans; Donepezil; Glycerylphosphorylcholine; Cognitive Dysfunction; Cognition Disorders; Cognition; Randomized Controlled Trials as Topic
PubMed: 36683513
DOI: 10.3233/JAD-221189 -
Frontiers in Neurology 2022As a common endovascular treatment for intracranial aneurysms, the pipeline embolization device (PED) is considered a standard treatment option, especially for large,...
INTRODUCTION
As a common endovascular treatment for intracranial aneurysms, the pipeline embolization device (PED) is considered a standard treatment option, especially for large, giant, wide-necked, or dissecting aneurysms. A layer of phosphorylcholine biocompatible polymer added to the surface of the PED can substantially improve this technology. This PED with shield technology (pipeline shield) is relatively novel; its early technical success and safety have been reported. We conducted a systematic literature review with the aim of evaluating the efficacy and safety of the pipeline shield.
METHODS
We searched the PubMed, Embase, and Cochrane databases, following the preferred reporting items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.
RESULTS
We selected five prospective and two retrospective studies for review. A total of 572 aneurysms were included; of these, 506 (88.5%) were unruptured. The antiplatelet regimens were heterogeneous. The rate of perioperative and postoperative complications was 11.1% [95% confidence interval (CI): 6.5-18.9%]. The adequate occlusion rate at 6 months was 73.9% (95% CI: 69.1-78.7%). The adequate occlusion rate of more than 12 months was 80.9% (95% CI: 75.1-86.1%). The mortality rate was 0.7% (95% CI: 0.2-1.5%). Subgroup analyses showed that aneurysm rupture status had no effect on aneurysm occlusion rate, patient morbidity, or mortality.
CONCLUSION
This review demonstrates the safety and efficacy of the pipeline shield for treating intracranial aneurysms. However, direct comparisons of the pipeline shield with other flow diverters are needed to better understand the relative safety and effectiveness of different devices.
PubMed: 36452166
DOI: 10.3389/fneur.2022.971664 -
European Journal of Medical Research Sep 2022Intrahepatic cholestasis of pregnancy (ICP) is a severe idiopathic disorder of bile metabolism; however, the etiology and pathogenesis of ICP remain unclear. (Review)
Review
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is a severe idiopathic disorder of bile metabolism; however, the etiology and pathogenesis of ICP remain unclear.
AIMS
This study comprehensively reviewed metabolomics studies related to ICP, to help in identifying the pathophysiological changes of ICP and evaluating the potential application of metabolomics in its diagnosis.
METHODS
Relevant articles were searched through 2 online databases (PubMed and Web of Science) from January 2000 to March 2022. The metabolites involved were systematically examined and compared. Pathway analysis was conducted through the online software MetaboAnalyst 5.0.
RESULTS
A total of 14 papers reporting 212 metabolites were included in this study. There were several highly reported metabolites: bile acids, such as glycocholic acid, taurochenodeoxycholic acid, taurocholic acid, tauroursodeoxycholic acid, and glycochenodeoxycholic acid. Dysregulation of metabolic pathways involved bile acid metabolism and lipid metabolism. Metabolites related to lipid metabolism include phosphatidylcholine, phosphorylcholine, phosphatidylserine, sphingomyelin, and ceramide.
CONCLUSIONS
This study provides a systematic review of metabolomics of ICP and deepens our understanding of the etiology of ICP.
Topics: Bile Acids and Salts; Cholestasis, Intrahepatic; Female; Humans; Metabolomics; Pregnancy; Pregnancy Complications
PubMed: 36104763
DOI: 10.1186/s40001-022-00802-z -
Materials (Basel, Switzerland) Mar 2021Researchers have developed novel nanocomposites that incorporate additional biomaterials with dimethylaminohexadecyl methacrylate (DMAHDM) in order to reduce secondary... (Review)
Review
Researchers have developed novel nanocomposites that incorporate additional biomaterials with dimethylaminohexadecyl methacrylate (DMAHDM) in order to reduce secondary caries. The aim of this review was to summarize the current literature and assess the synergistic antibacterial and remineralizing effects that may contribute to the prevention of secondary caries. An electronic search was undertaken in MEDLINE using PubMed, Embase, Scopus, Web of Science and Cochrane databases. The initial search identified 954 papers. After the removal of duplicates and screening the titles and abstracts, 15 articles were eligible for this review. The amalgamation of 2-methacryloyloxyethyl phosphorylcholine (MPC) and silver nanoparticles (AgNPs) with DMAHDM resulted in increased antibacterial potency. The addition of nanoparticles of amorphous calcium phosphate (NACP) and polyamidoamine dendrimers (PAMAM) resulted in improved remineralization potential. Further clinical studies need to be planned to explore the antibacterial and remineralizing properties of these novel composites for clinical success.
PubMed: 33808198
DOI: 10.3390/ma14071688 -
PLoS Neglected Tropical Diseases Mar 2021Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs).
METHODS
For this updated systematic review, we searched the following databases from 1st Jan 2016 through 2nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression.
RESULTS
We identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041-0.114; I2 = 81.4%; 95% prediction interval (PI): 0.001-2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368-1.021; I2 = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021-0.081; I2 = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244-1.355; I2 = 91.9%] compared to 0.043 [95% CI: 0.020-0.090; I2 = 62.5%] in 160 arms which excluded HIV co-infections.
CONCLUSION
Mortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.
Topics: Amphotericin B; Antimony; Antiprotozoal Agents; Deoxycholic Acid; Drug Combinations; Humans; Leishmaniasis, Visceral; Phosphorylcholine
PubMed: 33780461
DOI: 10.1371/journal.pntd.0009302 -
The Cochrane Database of Systematic... Aug 2020On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009.
OBJECTIVES
To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML).
SEARCH METHODS
We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome.
MAIN RESULTS
We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.
Topics: Administration, Oral; Adult; Antiprotozoal Agents; Azithromycin; BCG Vaccine; Female; Humans; Hyperthermia, Induced; Immunocompetence; Injections, Intramuscular; Injections, Intravenous; Interferon-gamma; Leishmaniasis Vaccines; Leishmaniasis, Cutaneous; Leishmaniasis, Mucocutaneous; Male; Meglumine Antimoniate; Pentoxifylline; Phosphorylcholine; Randomized Controlled Trials as Topic
PubMed: 32853410
DOI: 10.1002/14651858.CD004834.pub3 -
Antimicrobial Agents and Chemotherapy Jul 2019Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by parasites. Previous studies speculated that...
Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by parasites. Previous studies speculated that augmenting cytokines associated with a type 1 T-helper cell (Th1) response is necessary to combat severe forms of leishmaniasis, and it has been hypothesized that the antileishmanial drug miltefosine is capable of immunomodulation and induction of Th1 cytokines. A better understanding of the immunomodulatory effects of miltefosine is central to providing a rationale regarding synergistic mechanisms of activity to combine miltefosine optimally with other conventional and future antileishmanials that are currently under development. Therefore, a systematic literature search was performed to evaluate to what extent and how miltefosine influences the host Th1 response. Miltefosine's effects observed in both a preclinical and a clinical context associated with immunomodulation in the treatment of leishmaniasis are evaluated in this review. A total of 27 studies were included in the analysis. Based on the current evidence, miltefosine is not only capable of inducing direct parasite killing but also of modulating the host immunity. Our findings suggest that miltefosine-induced activation of Th1 cytokines, particularly represented by increased gamma interferon (IFN-γ) and interleukin 12 (IL-12), is essential to prevail over the -driven Th2 response. Differences in miltefosine-induced host-mediated effects between , animal model, and human studies are further discussed. All things considered, an effective treatment with miltefosine is acquired by enhanced functional Th1 cytokine responses and may further be enhanced in combination with immunostimulatory agents.
Topics: Animals; Antiprotozoal Agents; Cytokines; Humans; Immunomodulation; Leishmania; Leishmaniasis; Phosphorylcholine
PubMed: 31036692
DOI: 10.1128/AAC.02507-18