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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; Randomized Controlled Trials as Topic; Zalcitabine; Zidovudine
PubMed: 10908523
DOI: 10.1002/14651858.CD002038 -
Stroke Feb 2014The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis.
METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science. Twenty-two studies comprising 173 371 patients were included.
RESULTS
In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.73-0.88; P<0.0001; I(2)=28%) and of ischemic stroke or transient ischemic attack by 23% (RR, 0.77; 95% CI, 0.69-0.85; P<0.0001; I(2)=18%) without increasing the risk of intracranial hemorrhage. In the secondary prevention cohort, DAPT with aspirin and clopidogrel also reduced the relative risk of total stroke by 24% as compared with aspirin alone (RR, 0.76; 95% CI, 0.68-0.86; P<0.0001; I(2)=0%). DAPT with prasugrel or ticagrelor and aspirin versus DAPT with clopidogrel and aspirin was not associated with a risk reduction of stroke.
CONCLUSIONS
DAPT with clopidogrel and aspirin compared with aspirin effectively reduces the risk of total and ischemic stroke in the overall cohort consisting of patients with cardiovascular disease without increase in intracranial hemorrhage, as well as decreases the risk of a recurrent total stroke in patients with a previous stroke/transient ischemic attack. Our meta-analysis suggests that DAPT including low-dose aspirin (75-100 mg) and clopidogrel (75 mg) should be further investigated as a strategy to reduce recurrent strokes.
CLINICAL TRIAL REGISTRATION URL
http://www.crd.york.ac.uk/prospero. Unique identifier: CRD42011001596.
Topics: Adenosine; Aged; Aspirin; Cerebral Hemorrhage; Cerebrovascular Disorders; Clopidogrel; Cohort Studies; Data Interpretation, Statistical; Drug Therapy, Combination; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Population; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Receptors, Purinergic P2; Secondary Prevention; Stroke; Thiophenes; Ticagrelor; Ticlopidine; Vascular Diseases
PubMed: 24368560
DOI: 10.1161/STROKEAHA.113.002590 -
Rheumatology (Oxford, England) Jun 2010To critically evaluate the evidence regarding complementary and alternative medicines (CAMs) taken orally or applied topically for the treatment of FM. (Review)
Review
OBJECTIVE
To critically evaluate the evidence regarding complementary and alternative medicines (CAMs) taken orally or applied topically for the treatment of FM.
METHODS
Randomized controlled trials of FM using CAMs, in comparison with other treatments or placebo, published in English up to March 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 or placebo, and side effects were reported. The methodological quality of the primary studies was determined.
RESULTS
Single studies on four CAMs, and three on different approaches to homeopathic care were identified. Their methodological quality was moderate. The homeopathy studies were small, but each reported an improvement in pain. The effects of anthocyanidins, capsaicin and S-adenosylmethionine each showed at least one statistically significant improved outcome compared with placebo. However, the studies of anthocyanidins and capsaicin only demonstrated an improvement in a single outcome, sleep disturbance and tenderness, respectively, of several outcomes considered. No evidence of efficacy was found regarding Soy in a single study. Most of these CAMs were free of major adverse effects and usually associated with only minor adverse effects such as dizziness, nausea and stomach upsets.
CONCLUSION
There is insufficient evidence on any CAM, taken orally or applied topically, for FM. The small number of positive studies lack replication. Further high-quality trials are necessary to determine whether these initial findings can be supported by a larger evidence base.
Topics: Anthocyanins; Capsaicin; Complementary Therapies; Cost-Benefit Analysis; Fibromyalgia; Humans; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Glycine max; Treatment Outcome
PubMed: 20202927
DOI: 10.1093/rheumatology/keq025 -
Bone Marrow Transplantation Feb 2016We aimed to evaluate the efficacy and toxicity profile of busulfan-fludarabine (Bu-Flu) compared with busulfan-cyclophosphamide (Bu-Cy) as a preparative regimen for... (Comparative Study)
Comparative Study Meta-Analysis Review
We aimed to evaluate the efficacy and toxicity profile of busulfan-fludarabine (Bu-Flu) compared with busulfan-cyclophosphamide (Bu-Cy) as a preparative regimen for patients undergoing allogeneic hematopoietic cell transplantation. We performed a systematic review and meta-analysis of all comparative trials, both randomized controlled trials (RCTs) and non-randomized. Our search yielded 15 trials recruiting 1830 patients. Four trials were RCTs and 11 were either one-arm intervention trials compared with historical controls or retrospective studies. There was a lower risk for non-relapse mortality (NRM) at 100 days in patients given Bu-Flu regimen compared with those given Bu-Cy regimen (relative risk (RR) 0.56; 95% confidence interval (CI) 0.34-0.92, 8 trials); however, there were no differences in all-cause mortality at 100 days (RR 0.85; 95% CI 0.56-1.30, 9 trials) and at the end of study (RR 0.81; 95% CI 0.64-1.02, 13 trials). The risks of sinusoidal obstruction syndrome (SOS) and microbiologically documented infections were lower in patients given Bu-Flu regimen (RR 0.34; 95% CI 0.19-0.62, 8 trials and RR 0.79; 95% CI 0.64-0.97, 2 trials, respectively); however, risk for SOS was no longer lower when performing sensitivity analysis according to RCTs. Engraftment kinetics, risk of grade 3-4 mucositis, GvHD, relapse and NRM at the end of the study were all similar between the two groups. We conclude that both regimens have similar efficacy profiles, whereas toxicity is lower with the Bu-Flu regimen.
Topics: Allografts; Busulfan; Cyclophosphamide; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Randomized Controlled Trials as Topic; Survival Rate; Transplantation Conditioning; Vidarabine
PubMed: 26457908
DOI: 10.1038/bmt.2015.238 -
European Journal of Internal Medicine Jun 2022Aspirin is a cornerstone of preventive treatment for stroke recurrence, but during the last few years the role of dual antiplatelet therapy (DAPT) is much more emerging. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aspirin is a cornerstone of preventive treatment for stroke recurrence, but during the last few years the role of dual antiplatelet therapy (DAPT) is much more emerging.
OBJECTIVE
This systematic review aimed to compare early use of P2Y12 inhibitors (clopidogrel/ticagrelor) plus aspirin to aspirin alone for acute treatment and secondary prevention in acute non-cardioembolic minor ischemic stroke or TIA.
METHODS
A systematic search on MEDLINE and EMBASE was performed. Treatment effects were estimated with RRs and 95% CI. We used RevMan 5.4 for data analyses. We assessed methodological quality of selected studies according to Rob2 tools and quality of evidence with GRADE approach.
RESULTS
Four RCTs were included, enrolling 21,459 patients. Compared to aspirin alone, DAPT was superior in reducing stroke recurrence (RR 0.74, 95% CI 0.67-0.82, P <0.00001, absolute risk difference by 2%, NNT 50) and disabling stroke defined as mRS>2 (RR 0.84, 95% CI 0.75-0.95, P = 0.004), with no impact on all causes of mortality (RR 1.30, 95% CI 0.90-1.89, P = 0.16). An increased risk of major bleeding was emerged (RR 2.54, 95% CI 1.65-3.92, P <0.0001, absolute risk difference by 0,4%, NNH 250), in particular with ticagrelor, but there was no correlation between therapy duration and bleeding risk, as appeared from one-month (RR 3.06, 95% CI 1.64 to 5.69) and three-month (RR 2.09, 95% CI 1.18 to 3.69) follow-up analysis.
CONCLUSIONS
Early administration of P2Y12 inhibitors plus aspirin in patients with acute non-cardioembolic minor ischemic stroke or TIA reduced the incidence of ischemic stroke recurrence, impacting more significantly than the increased bleeding risk and influencing patients' quality of life by reducing disabling stroke.
Topics: Aspirin; Drug Therapy, Combination; Humans; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Quality of Life; Secondary Prevention; Stroke; Ticagrelor
PubMed: 35331593
DOI: 10.1016/j.ejim.2022.03.017 -
Cardiovascular Revascularization... Dec 2020Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor added to aspirin is considered the standard of care for patients with acute coronary syndrome (ACS) undergoing... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor added to aspirin is considered the standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Prasugrel and ticagrelor are commonly used P2Y12 inhibitors, and a few head-to-head randomized control trials (RCTs) have been performed. We performed a systematic review and meta-analysis of these RCTs to compare the efficacy and adverse effects between these two agents when used in patients with ACS undergoing PCI.
METHODS
We searched PubMed/MEDLINE and Cochrane library for RCTs comparing prasugrel to ticagrelor in ACS. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, major bleeding, and all bleeding event. Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI).
RESULTS
Six trials with 6807 patients were included. There were no significant difference of MACE (RR 0.93; 95% CI [0.72-1.20]; p = 0.59; I = 26%), all-cause mortality (RR 0.92; 95% CI [0.73-1.17]; p = 0.51; I = 0%), cardiovascular mortality (RR 0.99; 95% CI [0.75-1.31]; p = 0.96; I = 0%), MI (RR 0.87; 95% CI [0.60-1.27]; p = 0.48; I = 27%), stent thrombosis (RR 0.64; 95% CI [0.39-1.04]; p = 0.07; I = 0%), major bleeding (RR 0.94; 95% CI [0.70-1.26]; p = 0.68; I = 6%), and all bleeding event (RR 0.92; 95% CI [0.77-1.09]; p = 0.32; I = 0%) for prasugrel compared with ticagrelor.
CONCLUSION
There are no significant difference of MACE, all-cause mortality, cardiovascular mortality, MI, stent thrombosis, and bleeding between prasugrel and ticagrelor when added to aspirin among patients with ACS undergoing PCI.
Topics: Acute Coronary Syndrome; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome
PubMed: 32513604
DOI: 10.1016/j.carrev.2020.05.038 -
Current Medical Research and Opinion Aug 2018To assess the comparative efficacy and safety of cladribine tablets versus alternative disease modifying treatments (DMTs) in patients with active relapsing-remitting... (Comparative Study)
Comparative Study
OBJECTIVE
To assess the comparative efficacy and safety of cladribine tablets versus alternative disease modifying treatments (DMTs) in patients with active relapsing-remitting multiple sclerosis (RRMS), and in a subgroup with high disease activity (HRA + DAT), using systematic literature review (SLR) and network meta-analysis (NMA).
METHODS
MEDLINE, Embase, MEDLINE In-Process and CENTRAL databases were systematically searched to identify English-language publications of relevant studies of approved DMTs for RRMS. Searches were conducted from database inception to January 2017. Conference websites and trial registries were also searched. NMA considered the effects of DMTs on annualized relapse rate (ARR), confirmed disease progression (CDP), no evidence of disease activity (NEDA) and safety.
RESULTS
Of 10,825 articles retrieved and screened, 44 studies assessing 12 DMTs contributed to the NMA. In patients with active RRMS, cladribine tablets were associated with a significant 58% reduction in ARR versus placebo (p < .05); cladribine tablets were similar or significantly better than other DMT regimens and ranked fourth among DMTs, behind alemtuzumab, natalizumab and ocrelizumab. For CDP for 6 months and NEDA, improvements with cladribine tablets were significantly greater than those of placebo (p < .05), with no comparator DMT demonstrating significantly better results. Similar findings were reported in the HRA + DAT population. Overall adverse event risk for cladribine tablets did not differ significantly from that of placebo and most alternative DMTs.
CONCLUSION
In this first NMA to consider cladribine tablets, ocrelizumab and daclizumab for treatment of RRMS, cladribine tablets are a comparatively effective and safe alternative to other DMTs in both active RRMS and HRA + DAT populations.
Topics: Alemtuzumab; Cladribine; Humans; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Network Meta-Analysis; Tablets
PubMed: 29149804
DOI: 10.1080/03007995.2017.1407303 -
Journal of Cardiovascular Pharmacology May 2022The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy in patients, and in older patients, with acute coronary syndrome is... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy in patients, and in older patients, with acute coronary syndrome is reviewed. PubMed, Embase, the Cochrane Library, MEDLINE, and HTA databases were searched (September 2, 2020) for randomized controlled trials (RCTs). Pooled risk differences (clopidogrel minus ticagrelor) were estimated using random-effects meta-analyses, and certainty of evidence was assessed according to Grading of Recommendations Assessment, Development, and Evaluation. In all, 29 RCTs were identified. The risk difference for all-cause mortality was 0.6% (-0.03% to 1.3%), cardiovascular (CV) mortality: 0.6% (95% confidence interval: 0.01% to 1.1%), myocardial infarction (MI): 0.9% (0.4% to 1.3%), stent thrombosis: 0.7% (0.4 to 1.1%), clinically significant bleeding: -1.9% (-3.7% to -0.2%), major bleeding: -0.9% (-1.6% to -0.1%), and dyspnea: -5.8% (-7.7% to -3.8%). In older patients, there were no differences between the comparison groups regarding all-cause mortality, CV mortality, and MI, whereas the risk of clinically significant bleeding and major bleeding was lower in the clopidogrel group, -5.9% (-11 to -0.9%, 1 RCT) and -2.4% (-4.4% to -0.3%), respectively. Compared with ticagrelor, clopidogrel may result in little or no difference regarding all-cause mortality. Although not evident in older patients, it cannot be excluded that clopidogrel may be slightly less efficient in reducing the risk of CV mortality and MI, whereas ticagrelor is probably more efficacious in reducing the risk of stent thrombosis. Clopidogrel results in a reduced risk of dyspnea and clinically significant bleeding and in older people probably in a reduced risk of major bleeding.
Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dyspnea; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Thrombosis; Ticagrelor; Treatment Outcome
PubMed: 35170490
DOI: 10.1097/FJC.0000000000001233 -
Medicine Nov 2023To ascertain the efficacy and safety of cladribine, cytarabine, and filgrastim-based regimen in relapsed or refractory (R/R) AML patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To ascertain the efficacy and safety of cladribine, cytarabine, and filgrastim-based regimen in relapsed or refractory (R/R) AML patients.
METHODS
Clinical studies were searched in PubMed, Cochrane Library, Embase data. We selected available factors including complete remission (CR), overall response rate (ORR), overall survival (OS) to evaluate the efficacy, and early death (ED), and adverse events to evaluate safety.
RESULTS
15 records with 812 R/R AML patients were finally included and analyzed using the R software. Subgroups analysis was also conducted. The pooled CR rate for CLAG regimen, CLAG-M regimen, and CLAG combined with any other drugs regimen is 56% (95% CI: 46-66), 46% (95% CI: 34-56), 44% (95% CI: 26-64), respectively. The relapsed and refractory groups showed a CR rate of 68% (95% CI: 53-80), and 51% (95% CI: 45-58) with CLAG related regimens. As risk grade decreases, the pooled CR rate increases. Regarding the safety for CLAG-related protocols, systematic review was conducted.
CONCLUSION
The CLAG-related regimen is an effective and safe therapy for R/R AML patients, CLAG seems to have more superiority than CLAG combined therapy, though further studies including cladribine combination treatment protocols, are still needed to confirm our results further.
Topics: Humans; Filgrastim; Cladribine; Leukemia, Myeloid, Acute; Remission Induction; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Granulocyte Colony-Stimulating Factor
PubMed: 37933074
DOI: 10.1097/MD.0000000000034949 -
PloS One 2023The function of coronary microcirculation is an important factor in predicting the prognosis of patients with acute coronary syndrome (ACS) who receive percutaneous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The function of coronary microcirculation is an important factor in predicting the prognosis of patients with acute coronary syndrome (ACS) who receive percutaneous coronary intervention (PCI) therapy. Ticagrelor, a type of oral P2Y12 inhibitor, is widely prescribed to ACS patients and can improve prognosis compared to clopidogrel. However, the efficacy of ticagrelor on coronary microcirculation, compared to clopidogrel, remains unclear. The objective of this meta-analysis was to determine the efficacy of ticagrelor on coronary microcirculation.
METHODS
The PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were comprehensively searched to identify studies until November 2022. Data was pooled using the fixed effects model or random effects model based on the level of heterogeneity. Sensitivity analyses were performed to measure the effects of potential confounders.
RESULTS
After screening, 16 trials with a total of 3676 participants were ultimately included in the analysis. The meta-analysis revealed that compared to clopidogrel, patients receiving ticagrelor exhibited a more significant reduction in the IMR (WMD: -6.23, 95% CI: -8.41 to -4.04), a reduction in the cTFC (WMD: -1.88; 95% CI: -3.32 to -0.45), and greater increases in CFR (WMD: 0.38; 95% CI: 0.18 to 0.57), MBG (RR 1.29, 95% CI 1.12 to 1.48), and TIMI (RR 1.03, 95% CI 1.00 to 1.06).
CONCLUSION
Our findings suggest that, compared to clopidogrel, ticagrelor has a significant effect in reducing coronary microcirculatory resistance, enhancing coronary blood flow reserve, and improving myocardial perfusion.
Topics: Humans; Acute Coronary Syndrome; Clopidogrel; Ticagrelor; Microcirculation; Percutaneous Coronary Intervention
PubMed: 37643179
DOI: 10.1371/journal.pone.0289243