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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 -
Cancer Treatment Reviews Dec 2012Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against chlorambucil, but have not been directly compared against each other. There is currently no agreed upon standard therapeutic regimen for treatment-naïve CLL.
METHODS
We performed a systematic literature review to identify randomized controlled trials (RCTs) published prior to November 2011 of therapies for previously untreated CLL. We conducted a network meta-analysis using fixed and random effect statistical models to estimate differences between shape and scale parameters of progression-free survival (PFS) curves for each competing therapy. We used the parameter estimates and a Weibull distribution to project mean PFS for each therapy option.
RESULTS
Five RCTs were included in our comparison network. Overall, patients were younger (59-65 years), had good performance status based on the Eastern Cooperative Oncology Group scale (ECOG 0-1), and earlier stage disease (Rai 0-II or Binet A or B). The combination regimen fludarabine with cyclophosphamide and rituximab (FCR) was estimated to yield mean PFS of 76 months (95% CrI: 60, 91), FC 60 months (46, 73), fludarabine 38 months (27, 49), alemtuzumab 24 months (15, 32), and chlorambucil 23 months (15, 32).
CONCLUSION
Our results suggest that FCR has relatively higher potential of preventing disease progression in younger, healthier, treatment-naïve CLL patients and should be considered an optimal initial treatment strategy for this patient population. However, because estimates are based on model simulation, additional studies of FCR are necessary to clinically validate its therapeutic potential.
Topics: Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Randomized Controlled Trials as Topic; Rituximab; Vidarabine
PubMed: 22405931
DOI: 10.1016/j.ctrv.2012.02.006 -
Rheumatology (Oxford, England) May 2011Objectives. To critically evaluate the evidence regarding complementary and alternative medicine (CAM) taken orally or applied topically (excluding glucosamine and... (Review)
Review
Objectives. To critically evaluate the evidence regarding complementary and alternative medicine (CAM) taken orally or applied topically (excluding glucosamine and chondroitin) in the treatment of OA. Methods. Randomized clinical trials of OA using CAMs, in comparison with other treatments or placebo, published in English up to January 2009, were eligible for inclusion. They were identified using systematic searches of bibliographic databases and manual searching of reference lists. Information was extracted on outcomes, and statistical significance, in comparison with alternative treatment of placebo, and side effects were reported. The methodological quality of the primary studies was determined. Results. The present review found consistent evidence that capsaicin gel and S-adenosyl methionine were effective in the management of OA. There was also some consistency to the evidence that Indian Frankincense, methylsulphonylmethane and rose hip may be effective. For other substances with promising evidence, the evidence base was either insufficiently large or the evidence base was inconsistent. Most of the CAM compounds studied were free of major adverse effects. Conclusion. The major limitation in reviewing the evidence is the paucity of randomized controlled trials in the area: widening the evidence base, particularly for those compounds for which there is promising evidence, should be a priority for both researchers and funders.
Topics: Administration, Oral; Administration, Topical; Antirheumatic Agents; Capsaicin; Complementary Therapies; Humans; Osteoarthritis; S-Adenosylmethionine; Treatment Outcome
PubMed: 21169345
DOI: 10.1093/rheumatology/keq379 -
PloS One 2017Perioperative infusion of adenosine has been suggested to reduce the requirement for inhalation anesthetics, without causing serious adverse effects in humans. We... (Meta-Analysis)
Meta-Analysis
PURPOSE
Perioperative infusion of adenosine has been suggested to reduce the requirement for inhalation anesthetics, without causing serious adverse effects in humans. We conducted a meta-analysis of randomized controlled trials evaluating the effect of adenosine on postoperative analgesia.
METHODS
We retrieved articles in computerized searches of Scopus, Web of Science, PubMed, EMBASE, and Cochrane Library databases, up to July 2016. We used adenosine, postoperative analgesia, and postoperative pain(s) as key words, with humans, RCT, and CCT as filters. Data of eligible studies were extracted, which included pain scores, cumulative opioid consumption, adverse reactions, and vital signs. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed-effects or random-effects models, depending on the heterogeneity of the included trials.
RESULTS
In total, 757 patients from 9 studies were included. The overall effect of adenosine on postoperative VAS/VRS scores and postoperative opioid consumption was not significantly different from that of controls (P >0.1). The occurrence of PONV and pruritus was not statistically significantly different between an adenosine and nonremifentanil subgroup (P >0.1), but the rate of PONV occurrence was greater in the remifentanil subgroup (P <0.01). Time to first postoperative analgesic requirement in the adenosine group was not significantly difference from that of the saline group (SMD = 0.07, 95%CI: -0.28 to 0.41, P = 0.71); but this occurred significantly later than with remifentanil (SMD = 1.10, 95%CI: 2.48 to 4.06, P < 0.01). Time to hospital discharge was not significantly different between the control and adenosine groups (P = 0.78). The perioperative systolic blood pressure was significantly lower in the adenosine than in the control group in the mannitol subgroup (P < 0.01). The incidence of bradycardia, transient first- degree atrioventricular block, and tachycardia was not significantly different between the adenosine and control groups (P > 0.1).
CONCLUSION
Adenosine has no analgesic effect or prophylactic effect against PONV, but reduce systolic blood pressure and heart rates. Adenosine may benefit patients with hypertension, ischemic heart disease, and tachyarrhythmia, thereby improving cardiac function.
Topics: Adenosine; Adolescent; Adult; Aged; Analgesia; Analgesics, Opioid; Female; Humans; Male; Middle Aged; Pain, Postoperative; Young Adult
PubMed: 28333936
DOI: 10.1371/journal.pone.0173518 -
International Journal of Cardiology Jun 2017Adenosine may unmask dormant PV conduction and facilitate consolidation of PV isolation. We performed a meta-analysis to determine the impact of adenosine administration... (Meta-Analysis)
Meta-Analysis Review
AIMS
Adenosine may unmask dormant PV conduction and facilitate consolidation of PV isolation. We performed a meta-analysis to determine the impact of adenosine administration on clinical outcomes in patients undergoing PVI.
METHODS
References and electronic databases reporting AF ablation and adenosine following PVI were searched through to 22nd November 2015. The impact of adenosine on freedom from AF was assessed in twenty publications after radiofrequency ablation (RFA), and in four publications after cryoablation to achieve PVI. Relative risks were calculated and combined in a meta-analysis using random effects modeling.
RESULTS
In patients undergoing RFA with adenosine challenge, there was a significant reduction in freedom from AF in patients with versus without adenosine induced reconnection (RR 0.86; 95%CI 0.77-0.98; p=0.02) particularly if no further ablation was performed (RR 0.66; 95%CI 0.50-0.87; p<0.01). There was no difference when comparing outcomes in studies of routine adenosine challenge vs no adenosine (RR 1.07; 95%CI 0.93-1.22; p=0.36). There was a non-significant trend to an increase in freedom from AF in patients receiving routine adenosine challenge (RR 1.18 95%CI 0.99-1.42; p=0.07) in non-randomized studies using cryoablation.
CONCLUSION
Adenosine induced PV reconnection following PVI is associated with a significant increase in AF recurrence, particularly if the reconnection sites are not targeted for ablation. The routine use of adenosine may be beneficial in AF ablation if given early post-PVI, at sufficient dose and reconnection is ablated.
Topics: Adenosine; Atrial Fibrillation; Catheter Ablation; Cryosurgery; Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic
PubMed: 28089454
DOI: 10.1016/j.ijcard.2017.01.070 -
Acta Psychiatrica Scandinavica May 2019Obsessive-compulsive disorder (OCD) is a chronic, prevalent, and highly impairing psychiatric illness. Although the pathophysiology of OCD remains unknown, pathways... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Obsessive-compulsive disorder (OCD) is a chronic, prevalent, and highly impairing psychiatric illness. Although the pathophysiology of OCD remains unknown, pathways involved in oxidative and nitrosative stress (O&NS) have been implicated. The present study aims to systematically review the literature for quantitative evidence that patients with OCD have altered measures of blood O&NS markers.
METHODS
Independent random-effects meta-analyses using standardized mean differences were conducted to assess each marker separately. Additionally, data from multiple markers were pooled together in a meta-analysis for measures of oxidant activity and another for measures of antioxidant activity.
RESULTS
Thirteen studies met inclusion criteria, involving 433 OCD patients and 459 controls. Eleven blood O&NS markers were eligible for independent quantitative analyses. We found that, in OCD patients, the oxidant markers 8-hydroxydeoxyguanosine and malondialdehyde, and the antioxidants glutathione peroxidase and superoxide dismutase, were significantly increased while total antioxidant status, vitamin C, and vitamin E were significantly decreased, when comparing with controls. Regarding pooled meta-analyses, we found a statistically significant increase in oxidant markers, but non-significant results regarding antioxidant markers.
CONCLUSIONS
Our meta-analysis suggests that OCD patients have a systemic oxidative imbalance that is not adequately buffered by the antioxidant system. Additional studies are needed in order to support this association.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Ascorbic Acid; Biomarkers; Case-Control Studies; Child; Evaluation Studies as Topic; Female; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Middle Aged; Nitrosative Stress; Obsessive-Compulsive Disorder; Oxidative Stress; Superoxide Dismutase; Vitamin E; Young Adult
PubMed: 30873609
DOI: 10.1111/acps.13026 -
Cardiology 2022There have been inconsistent data on the direct comparison of prasugrel and ticagrelor. This meta-analysis was conducted to summarize the current available evidence. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
There have been inconsistent data on the direct comparison of prasugrel and ticagrelor. This meta-analysis was conducted to summarize the current available evidence.
METHODS
We performed a meta-analysis (PROSPERO-registered CRD42020166810) of randomized trials up to February 2020 that compared prasugrel and ticagrelor in acute coronary syndrome with respect to the composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death and secondary endpoints including MI, stroke, cardiovascular death, major bleeding (Bleeding Academic Research Consortium (BARC) type 2 or above), stent thrombosis, all-cause death, and other safety outcomes.
RESULTS
Of the 11 eligible RCTs with 6,098 patients randomized to prasugrel (n = 3,050) or ticagrelor (n = 3,048), 180 and 207 had the composite endpoint events in the prasugrel arm and the ticagrelor arm, respectively, over a weighted mean follow-up period of 11 ± 2 months. Compared with prasugrel, the ticagrelor group had similar risk in the primary composite endpoint (risk ratio [RR] = 1.17; 95% CI = 0.96-1.42; p = 0.12, I2 = 0%). Compared to prasugrel, there was no significant difference associated with the ticagrelor groups with respect to stroke (RR = 1.05; 95% CI = 0.66-1.67; p = 0.84, I2 = 0%), cardiovascular death (RR = 1.01; 95% CI = 0.75-1.36; p = 0.95, I2 = 0%), BARC type 2 or above bleeding (RR = 1.16; 95% CI = 0.89-1.52; p = 0.26, I2 = 0%), stent thrombosis (RR = 1.58; 95% CI = 0.90-2.76; p = 0.11, I2 = 0%), and all-cause death (RR = 1.10; 95% CI = 0.86-1.43; p = 0.45, I2 = 0%) except MI (RR = 1.38; 95% CI = 1.05-1.81; p = 0.02, I2 = 0%) Conclusion: Compared with prasugrel, ticagrelor did not reduce the primary composite endpoint of MI, stroke, and cardiovascular death at a weighted mean follow-up of 11 months. There was no significant difference between the secondary outcomes except MI.
Topics: Acute Coronary Syndrome; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome
PubMed: 34743081
DOI: 10.1159/000520673 -
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 -
The Cochrane Database of Systematic... Jun 2013Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The first version of this review, published in 2001, and including nine randomised controlled trials involving 227 women, concluded that there was insufficient evidence to recommend any of the interventions alone or in combination. This is the first update.
OBJECTIVES
To evaluate the effectiveness and safety of therapeutic and delivery interventions in women with cholestasis of pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 February 2013) and reference lists of identified studies.
SELECTION CRITERIA
Randomised controlled trials that compared two intervention strategies for women with a clinical diagnosis of obstetric cholestasis.
DATA COLLECTION AND ANALYSIS
The review authors independently assessed trials for eligibility and risk of bias. We independently extracted data and checked these for accuracy.
MAIN RESULTS
We included 21 trials with a total of 1197 women. They were mostly at moderate to high risk of bias. They assessed 11 different interventions resulting in 15 different comparisons.Compared with placebo, ursodeoxycholic acid (UDCA) showed improvement in pruritus in five (228 women) out of seven trials. There were no significant differences in instances of fetal distress in the UDCA groups compared with placebo (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.22 to 2.02; five trials, 304 women; random-effects analysis: T² = 0.74; I² = 48%). There were significantly fewer total preterm births with UDCA (RR 0.46; 95% CI 0.28 to 0.73; two trials, 179 women). The difference for spontaneous preterm births was not significant (RR 0.99; 95% CI 0.41 to 2.36, two trials, 109 women).Two trials (48 women) reported lower (better) pruritus scores for S-adenosylmethionine (SAMe) compared with placebo, while two other trials of 34 women reported no significant differences between groups.UDCA was more effective in improving pruritus than either SAMe (four trials; 133 women) or cholestyramine (one trial; 84 women), as was combined UDCA+SAMe when compared with placebo (one trial; 16 women) and SAMe alone (two trials; 68 women). However, combined UDCA+SAMe was no more effective than UDCA alone in regard to pruritus improvement (one trial; 53 women) and two trials (80 women) reported data were insufficient to draw any conclusions from. In one trial comparing UDCA and dexamethasone (83 women), a significant improvement with UDCA was seen only in a subgroup of women with severe obstetric cholestasis (23 women).Danxiaoling significantly improved pruritus in comparison to Yiganling. No significant differences were seen in pruritus improvement with other interventions.Eight trials reported fetal or neonatal deaths, with two deaths reported overall (both in the placebo groups).Women receiving UDCA and cholestyramine experienced nausea, vomiting and diarrhoea. Guar gum caused mild abdominal distress, diarrhoea and flatulence during the first days of treatment. Women found charcoal suspension unpleasant to swallow. Dexamethasone caused nausea, dizziness and stomach pain in one woman.One trial (62 women) looked at the timing of delivery intervention. There were no stillbirths or neonatal deaths in 'early delivery' or the 'await spontaneous labour' group. There were no significant differences in the rates of caesarean section, meconium passage or admission to neonatal intensive care unit between the two groups.
AUTHORS' CONCLUSIONS
Different approaches to assessing and reporting pruritus precluded pooling of trials comparing the effects of UDCA versus placebo on pruritus, but examination of individual trials suggests that UDCA significantly improves pruritus, albeit by a small amount. Fewer instances of fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant. Large trials of UDCA to determine fetal benefits or risks are needed.A single trial was too small to rule in or out a clinically important effect of early term delivery on caesarean section.There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction (YCHD), Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy.
Topics: Charcoal; Cholagogues and Choleretics; Cholestasis; Cholestyramine Resin; Drugs, Chinese Herbal; Female; Galactans; Humans; Mannans; Plant Gums; Pregnancy; Pregnancy Complications; Pruritus; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Ursodeoxycholic Acid
PubMed: 23794285
DOI: 10.1002/14651858.CD000493.pub2 -
The Cochrane Database of Systematic... 2000Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC). (Review)
Review
BACKGROUND
Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC).
OBJECTIVES
To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival.
SEARCH STRATEGY
Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts.
SELECTION CRITERIA
Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events.
DATA COLLECTION AND ANALYSIS
Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials.
MAIN RESULTS
Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009).
REVIEWER'S CONCLUSIONS
The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.
Topics: Adult; Anti-HIV Agents; Didanosine; Drug Administration Schedule; Drug Therapy, Combination; HIV Infections; Humans; Zalcitabine; Zidovudine
PubMed: 10796851
DOI: 10.1002/14651858.CD002038