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The Journal of Headache and Pain Apr 2022Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are... (Review)
Review
BACKGROUND
Adenosine is a purinergic signaling molecule with a wide range of physiological functions including anti- and pronociceptive properties. Adenosine receptors are expressed in the trigeminovascular system, and adenosine receptor antagonist, caffeine, relieves migraine headache. We performed a systematic review of the literature of preclinical data addressing the role of adenosine in migraine pathophysiology.
METHODS
PubMed and EMBASE were searched for pre-clinical studies on the role of adenosine in migraine pathophysiology on September 5, 2021.
RESULTS
A total of 2510 studies were screened by title and abstract. Of these, thirteen pre-clinical studies evaluating adenosine, adenosine A1, A2A and A3 receptors were included. These studies showed that adenosine signaling pathway is involved in controlling vascular tone. Furthermore, electrical stimulation of the trigeminal ganglion modulates the expression of adenosine A and A receptors in the trigeminal ganglion and trigeminal nucleus caudalis implicating adenosine signaling pathway in pain transmission.
CONCLUSION
Preclinical studies showed that adenosine has a dual effect on vasodilation and trigeminal pain pathway due to different receptor activation, suggesting a possible role of adenosine in migraine pathophysiology. Studies investigating pharmacological characteristics of subtypes of adenosine receptors are needed to further elucidate their role as a potential target for migraine treatment.
Topics: Adenosine; Humans; Migraine Disorders; Signal Transduction; Trigeminal Ganglion; Trigeminal Nuclei
PubMed: 35382738
DOI: 10.1186/s10194-022-01412-0 -
Multiple Sclerosis and Related Disorders Jan 2023Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and... (Review)
Review
BACKGROUND
Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and Year 2. Most patients achieve sustained efficacy with CladT, but a small proportion may experience new disease activity (DA). Following completion of the indicated dose, physicians may have questions relating to the long-term management of these patients. Since the EU approval of CladT over 5 years ago, real-world evidence (RWE) is increasing and may provide some insights and guidance for clinical practice. We describe a systematic literature review (SLR) of RWE and provide expert opinions relating to six questions regarding the long-term use of CladT.
METHODS
Pertinent clinical questions were developed by a steering committee (SC) of 14 international multiple sclerosis (MS) experts regarding breakthrough DA in Year 1, new DA after 2 years or more of treatment, long-term management of stable patients, and whether additional courses of CladT may be required or safe. An SLR was performed in EMBASE and PubMed using the population, intervention, comparators, outcomes, study design (PICOS) framework to identify relevant studies within the last 15 years. Searches of key congress proceedings for the last 2-3 years were also performed. Following review of the results and RWE, the SC drafted and agreed on expert opinion statements for each question.
RESULTS
A total of 35 publications reporting RWE for CladT were included in this review. In the real world, breakthrough DA in Year 1 is of low incidence (1.1-21.9%) but can occur, particularly in patients switching from anti-lymphocyte trafficking agents. In most patients, this DA did not lead to treatment discontinuation. Reported rates of DA after the full therapeutic effect of CladT has been achieved (end of Year 2, 3 or 4) range from 12.0 to 18.7% in the few studies identified. No RWE was identified to support management decisions for stable patients in Year 5 or later. Views among the group were also diverse on this question and voting on expert opinion statements was required. Only two studies reported the administration of additional courses of CladT, but detailed safety outcomes were not provided.
CONCLUSIONS
RWE for the long-term use of CladT in the treatment of RMS is increasing, however, gaps in knowledge remain. Where possible, the RWE identified through the SLR informed expert statements, but, where RWE is still lacking, these were based solely on experiences and opinion, providing some guidance on topics and questions that occur in daily clinical practice. More real-world studies with longer-term follow-up periods are needed and highly anticipated.
Topics: Humans; Cladribine; Multiple Sclerosis; Expert Testimony; Lymphocytes; Tablets; Recurrence; Immunosuppressive Agents
PubMed: 36565573
DOI: 10.1016/j.msard.2022.104459 -
Journal of Thrombosis and Haemostasis :... Jun 2015Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity.
OBJECTIVES
To compare the impact of ticagrelor and prasugrel on high on-treatment platelet reactivity (HTPR).
METHODS
The PubMed and Cochrane databases were searched for eligible studies in December 2014. Studies were eligible if they compared ticagrelor and prasugrel regarding high on-treatment platelet reactivity (HTPR). Pooled estimates were calculated by using a random-effects model with 95% confidence intervals.
RESULTS
We included 14 studies and 1822 patients: 805 and 1017 in the ticagrelor and prasugrel groups, respectively. The rate of HTPR was significantly lower in the ticagrelor group: 1.5% vs. 9.8% (RR = 0.27 [0.14-0.50]). The pre-specified analysis focusing on randomized trials (n = 10) showed consistent results (RR = 0.27 [0.12-0.60]).
CONCLUSION
Our results suggest that ticagrelor allows a higher platelet reactivity inhibition as compared with prasugrel and leads to a further decrease in the rate of HTPR.
Topics: Adenosine; Blood Platelets; Chi-Square Distribution; Drug Resistance; Heart Diseases; Humans; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Risk Factors; Ticagrelor; Treatment Outcome
PubMed: 25809392
DOI: 10.1111/jth.12907 -
Drug Safety Nov 2022Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is...
INTRODUCTION
Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is scarce.
OBJECTIVE
We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatric population.
METHODS
We included original articles conducted in a paediatric population (< 18 years) in which a therapeutic intervention was described to manage APAP or idiosyncratic DILI. Findings were summarized based on age groups (preterm newborn neonates, term and post-term neonates, infants, children and adolescents).
RESULTS
Overall, 25 publications (fifteen case reports, six case series and four retrospective cohort studies) were included, including a total of 140 paediatric DILI cases, from preterm newborn neonates to adolescents. N-acetylcysteine was used to treat 19 APAP cases. N-acetylcysteine (n = 14), ursodeoxycholic acid (n = 3), corticosteroids (n = 31), carnitine (n = 16) and the combination of glycyrrhizin, reduced glutathione, polyene phosphatidylcholine and S-adenosylmethionine (n = 31) were the therapeutic options for treating idiosyncratic DILI. The molecular adsorbent recirculating system was used in the management of either APAP (n = 4) or idiosyncratic DILI (n = 2), while 20 paediatric ALF cases received continuous renal replacement therapy.
CONCLUSIONS
This systematic review identified DILI in the paediatric population who have received specific treatment. These interventions appear to be mainly extrapolated from low-quality evidence from the adult population. Thus, there is a need for high-quality studies to test the efficacy of known and novel therapies to treat DILI specifically addressed to the paediatric population. PROSPERO registration number CRD42021214702.
Topics: Acetaminophen; Acetylcysteine; Adolescent; Adrenal Cortex Hormones; Adult; Carnitine; Chemical and Drug Induced Liver Injury; Child; Drug-Related Side Effects and Adverse Reactions; Glutathione; Glycyrrhizic Acid; Humans; Infant, Newborn; Liver; Liver Failure, Acute; Retrospective Studies; S-Adenosylmethionine; Ursodeoxycholic Acid
PubMed: 36006605
DOI: 10.1007/s40264-022-01224-w -
Journal of Women's Health (2002) May 2017Oxidative stress may play an important role in both initiation and progression of breast cancer. We conducted the first systematic epidemiologic review to summarize the... (Review)
Review
BACKGROUND
Oxidative stress may play an important role in both initiation and progression of breast cancer. We conducted the first systematic epidemiologic review to summarize the published literature on oxidative stress biomarkers and breast cancer.
MATERIALS AND METHODS
We implemented systematic search strategies to identify published studies of oxidative stress biomarkers and (1) risk of developing breast cancer and (2) breast cancer prognosis using the PRISMA statement guidelines.
RESULTS
We identified eleven case-control studies of oxidative stress biomarkers and breast cancer. Biomarkers utilized varied and menopausal status was a key modifying factor. Across three nested case-control studies with biomarkers measured before diagnosis, one reported increased risk of postmenopausal breast cancer in association with 8-oxodG (DNA damage biomarker), while two (one of F-isoprostanes and one of fluorescent oxidation products) reported inverse associations for premenopausal breast cancer only. We identified eight prognostic studies. Two reported associations for lipid peroxidation and breast cancer prognosis; results for other studies were null.
CONCLUSIONS
DNA damage may increase risk of breast cancer among postmenopausal women, while lipid peroxidation may be inversely associated with premenopausal breast cancer. Lipid peroxidation may be associated with survival after breast cancer diagnosis; however, results require evaluation in large, prospective cohort studies.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers, Tumor; Breast Neoplasms; Deoxyguanosine; Female; Humans; Middle Aged; Oxidative Stress; Prognosis; Risk Factors; Survival Analysis
PubMed: 28151039
DOI: 10.1089/jwh.2016.5973 -
Multiple Sclerosis and Related Disorders Dec 2022The Coronavirus 19 pandemic has raised new relevant questions regarding the management of patients with multiple sclerosis (pwMS) treated with different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Coronavirus 19 pandemic has raised new relevant questions regarding the management of patients with multiple sclerosis (pwMS) treated with different immunosuppressive and immunomodulant drugs. In most COVID-19 outcomes analyses, due to the small available sample size, patients treated with cladribine were grouped with patients treated with other treatments.
METHODS
Three major databases (PubMed, Scopus and Web of Science) and the most recent MS congress libraries were searched for extracting original articles on COVID-19 and multiple sclerosis. The key inclusion criteria were the presence of data on pwMS treated with cladribine and with documented positivity for COVID-19. The quality of the included studies was evaluated using a modified version of the Dutch Cochrane center critical review checklist proposed by MOOSE. A common-effect meta-analysis was used for estimating the pooled proportion of patients with severe events (hospitalizations, pneumonia, ICU admissions and deaths) and heterogeneity was assessed by the I statistic.
RESULTS
13 articles were included in the analysis and the median quality of the articles reached a level of 4. The selected studies included 5138 patients with COVID-19, of whom 107 (2.1%) were treated with cladribine. Pooled estimates of hospitalization and death were 9.36% and 0% for patients treated with cladribine, 14.98% and 2.66% for pwMS under other treatments.
CONCLUSION
These results indicate that pwMS treated with cladribine are not at a greater risk of developing a severe form of COVID-19.
REGISTRATION
The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022329464).
Topics: Humans; Cladribine; Multiple Sclerosis; COVID-19; Pandemics; Immunosuppressive Agents
PubMed: 36137347
DOI: 10.1016/j.msard.2022.104156 -
PloS One 2015It has been well established that S-adenosyl-L-methionine (SAMe) is the principal methyl donor in methyltransferase reactions and that SAMe supplementation restores... (Meta-Analysis)
Meta-Analysis Review
It has been well established that S-adenosyl-L-methionine (SAMe) is the principal methyl donor in methyltransferase reactions and that SAMe supplementation restores hepatic glutathione (GSH) deposits and attenuates liver injury. However, the effectiveness of SAMe therapy in chronic liver disease has not been adequately addressed. We searched globally recognized electronic databases, including PubMed, the Cochrane Database and EMBASE, to retrieve relevant randomized controlled trials (RCTs) of chronic liver disease published in the past 20 years. We then performed a systematic review and meta-analysis of the enrolled trials that met the inclusion criteria.The results showed that twelve RCTs from 11 studies, which examined 705 patients, were included in this research. For liver function, certain results obtained from data synthesis and independent comparisons demonstrated significant differences between the levels of total bilirubin (TBIL) and aspartate transaminase (AST). However, no studies identified significant differences regarding alanine transaminase (ALT) levels. An analysis of the adverse events and long-term prognosis also indicated no significant differences between the SAMe and the placebo groups. In a subgroup analysis of gravidas and children, several of the included data indicated that there was a significant difference in the pruritus score. Furthermore, the results regarding ursodeoxycholic acid (UDCA) and stronger neo-minophagen C (SNMC) indicated that both treatments were more effective than SAMe was in certain chronic liver diseases. These findings suggest that SAMe could be used as the basis of a medication regimen for liver function improvement because of its safety. However, SAMe also demonstrated limited clinical value in the treatment of certain chronic liver diseases.
Topics: Age Factors; Chronic Disease; Humans; Liver Diseases; Liver Function Tests; S-Adenosylmethionine; Treatment Outcome
PubMed: 25774783
DOI: 10.1371/journal.pone.0122124 -
Ecotoxicology and Environmental Safety Nov 2023Oxidative stress (OS) constitutes a pivotal factor in the initiation and progression of lipopolysaccharide (LPS) challenges in broiler chickens. Increasing studies have... (Meta-Analysis)
Meta-Analysis Review
Oxidative stress (OS) constitutes a pivotal factor in the initiation and progression of lipopolysaccharide (LPS) challenges in broiler chickens. Increasing studies have demonstrated that Alleviation of oxidative stress seems to be a reasonable strategy to alleviate LPS-mediated afflictions in broilers. Nonetheless, the relationship between OS-related indicators and exposure to LPS remains a topic of debate. The aim of this investigation was to precisely and holistically evaluate the effect of LPS exposure on OS-associated markers. We conducted a systematic search of four electronic databases-PubMed, Web of Science, Scopus, and Cochrane for relevant studies, and a total of 31 studies were included. The overall results showed that the LPS treatment significantly increased the levels of oxygen radicals and their products, such as malondialdehydes (MDA), reactive oxygen species (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG), while significantly reduced the levels of antioxidants, such as total antioxidative capacity (T-AOC), total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH), in the chickens. Intriguingly, though the observed trends in alterations were not strictly correlated with LPS concentrations, the enzyme activity levels were indeed influenced by the concentration of LPS. This observation highlights the complex relationship between LPS exposure and the body's antioxidant response. Despite some limitations, all the included studies were deemed credible. Subgroup evaluations revealed that the jejunum and duodenum has demonstrated stronger antioxidant capability compared to other tissues. Overall, our study presents compelling evidence that exposure to LPS induces significant OS in chickens. And we also found that the extent of OS was related to LPS doses, target tissues, and dietary ingredients.
Topics: Animals; Antioxidants; Chickens; Lipopolysaccharides; Oxidative Stress; Glutathione; Reactive Oxygen Species; 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Dietary Supplements
PubMed: 37866038
DOI: 10.1016/j.ecoenv.2023.115606 -
Journal of Thrombosis and Haemostasis :... Jun 2019Early administration of P2Y12-receptor inhibitors is recommended in all patients with acute coronary syndrome undergoing invasive management, with the aim to achieve the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early administration of P2Y12-receptor inhibitors is recommended in all patients with acute coronary syndrome undergoing invasive management, with the aim to achieve the fastest and most effective platelet inhibition. Several trials investigated alternative methods of P2Y12-receptor inhibitor administration (mainly chewed or crushed) aimed at ensuring faster and higher platelet inhibition. Thus, we decided to perform a systematic review and meta-analysis analyzing efficacy and safety of alternative P2Y12-receptor inhibitor administration strategies.
METHODS
Systematic research was performed on Pubmed, Cochrane Library, Biomed Central, and Web of Science databases. We included randomized or observational trials testing at least one P2Y12-receptor inhibitor alternative administration. The primary outcome of the study was the value of the platelet reactivity unit (PRU) at 1 h after drug administration, assessed by VerifyNow P2Y12 test (Accumetrics, Inc., San Diego, CA). Secondary outcomes were adverse bleeding events (safety outcome).
RESULTS AND DISCUSSION
Fourteen studies were selected for qualitative analysis. Five studies, all focused on ticagrelor, were selected for quantitative efficacy analyses. These five studies compared the administration of crushed/chewed ticagrelor 180 mg loading dose (LD) with the standard whole tablets LD. The pooled mean difference between the two administrations was -59.24 PRU (95% CI from -30.61 to -87.87 PRU) in favor of the crushed/chewed administration, corresponding to a 25% mean relative PRU reduction between alternative and standard P2Y12-receptor inhibitor administrations at 1 h after drug intake. A similar relationship was found in other studies on alternative administration of clopidogrel and prasugrel, not included in the quantitative analysis.
Topics: Acute Coronary Syndrome; Administration, Oral; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Safety; Ticagrelor; Treatment Outcome
PubMed: 30884109
DOI: 10.1111/jth.14434 -
Journal of Interventional Cardiology 2022This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS).
BACKGROUND
The safety and efficacy of DAPT in elderly patients with ACS is not well characterized.
METHODS
We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public.
RESULTS
Our search yielded 660 potential studies. We included 8 studies reporting on 29,217 patients. There was a higher risk of bleeding event rates in elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 1.17 (95% CI 1.08 to 1.27, < 0.05). There was no difference in primary efficacy endpoint rates between elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 0.85 (95% CI 0.68 to 1.07, =0.17).
CONCLUSIONS
This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.
Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Ticagrelor; Treatment Outcome
PubMed: 36176329
DOI: 10.1155/2022/3111840