scholarly journals A review of the treatment options for skin rash induced by EGFR-targeted therapies: Evidence from randomized clinical trials and a metaanalysis

2013 ◽  
Vol 47 (2) ◽  
pp. 166-175 ◽  
Author(s):  
Janja Ocvirk ◽  
Steffen Heeger ◽  
Philip McCloud ◽  
Ralf-Dieter Hofheinz
Keyword(s):  
Skin Rash ◽  
Vitamin K ◽  
Targeted Therapies ◽  
Literature Search ◽  
Randomized Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Evidence Based ◽  
Targeted Agents ◽  
Oral Antibiotics

Background.Agents targeting the epidermal growth factor receptor (EGFR) are amongst the most extensively used of the targeted agents in the therapy of some of the most common solid tumors. Although they avoid many of the classic side effects associated with cytotoxic chemotherapy, they are associated with unpleasant cutaneous toxicities which can affect treatment compliance and impinge on patient quality of life. To date, despite a plethora of consensus recommendations, expert opinions and reviews, there is a paucity of evidence-based guidance for the management of the skin rash that occurs in the treatment of patients receiving EGFR-targeted therapies.Methods.A literature search was conducted as a first step towards investigating not only an evidence-based approach to the management of skin rash, but also with a view to designing future randomized trials. Results. The literature search identified seven randomized trials and a meta-analysis was conducted using the data from four of these trials involving oral antibiotics. The meta-analysis of the data from these four trials suggests that prophylactic antibiotics might reduce the relative risk of severe rash associated with EGFR-targeted agents by 42-77%. Vitamin K cream was also identified as having a potential role in the management EGFR-targeted agent induced rash.Conclusions.This review and meta-analysis clearly identify the need for further randomized studies of the role of oral antibiotics in this setting. The results of the ongoing randomized trials of the topical application of vitamin K cream plus or minus doxycycline and employing prophylactic versus reactive strategies are eagerly awaited.

Abstract 11526: Intraprocedural Thrombotic Events During PCI for ACS Are Associated With Increased Adverse Ischemic Events at 30 Days: A Meta-Analysis of Randomized Trials

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ramez Nairooz ◽  
Partha Sardar ◽  
Saurav Chatterjee ◽  
Zubair Ahmed ◽  
Dmitriy N Feldman
Keyword(s):  
Clinical Outcomes ◽  
Stent Thrombosis ◽  
Literature Search ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Repeat Revascularization ◽  
Coronary Syndrome ◽  
Reported Data ◽  
Ischemic Events

Background: Data regarding intraprocedural thrombotic events (IPTE) including slow reflow or no reflow, distal embolization, intraprocedural stent thrombosis and abrupt vessel closure during PCI for acute coronary syndrome (ACS) are scarce. Their association with subsequent adverse ischemic events needs further investigation. Aim: To evaluate effect of IPTE on in-hospital and at 30-days clinical outcomes after PCI for ACS. Hypothesis: IPTE during PCI are associated with adverse ischemic events while in-hospital and at 30 days. Methods: We performed a literature search of all published full-length articles of randomized trials that reported data on patients with IPTE compared with no IPTE during PCI for patients with ACS. We calculated odd ratios via random effects model for in-hospital ischemic outcomes and 30 day outcomes. Results: Our literature search yielded 3 randomized trials reporting clinical outcomes with IPTE and no IPTE for ACS patients undergoing PCI: ACUITY, HORIZONS-AMI and EARLY-ACS trials. We report clinical outcomes (in-hospital and at 30 days) in 8,043 patients in total, of those 673 had IPTE. At 30 days, patients with IPTE had more major adverse cardiovascular events (MACE) (Odds ratio (OR) 3.97, 95% Confidence interval (CI) [1.81-8.69]; p=0.0006), mortality (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003), myocardial infarction (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003), repeat revascularization (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003), total stent thrombosis (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003) and non-CABG related major bleeding (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003) than those with no IPTE. Similarly, in-hospital clinical outcomes were all significantly higher in patients with IPTE than those without. Conclusion: IPTE during PCI is associated with more adverse ischemic events, including mortality, both in-hospital and at 30 days.

Incidence of severe nephrotoxicity with cisplatin vs. non-cisplatin regimens: A meta-analysis with sub-group analyses based on renal eligibility criteria.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15549-e15549
Author(s):  
Arati Dahal ◽  
Brandon Kyle Bellows ◽  
Guru Sonpavde ◽  
Matt D. Galsky ◽  
Neeraj Agarwal
Keyword(s):  
Renal Function ◽  
Fixed Effects ◽  
Literature Search ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Exclusion Criterion ◽  
Eligibility Criteria ◽  
Subgroup Analyses ◽  
Grade 3 ◽  
Re Methods

e15549 Background: Serum Creatinine (SCr) is commonly used to screen patients for eligibility in trials of the nephrotoxic drug cisplatin despite the fact that glomerular filtration rate (GFR) is known to better estimate renal function. The objective of this meta-analysis was to indirectly compare incidence of nephrotoxicity in trials using cisplatin for treatment of solid tumors when renal function was assessed using SCr or GFR for eligibility criteria. Methods: A literature search was conducted in PubMed to identify randomized trials comparing cisplatin to non-cisplatin containing chemotherapy regimens. Studies were included if they were performed from 1990-2010, used SCr or GFR as eligibility criteria, and reported incidence of WHO or NCI grade ≥3 nephrotoxic events for both treatment arms. Review articles, non-randomized trials, observational, phase I, studies without a comparator group, or not reported in English were excluded. The relative risk (RR) of grade ≥3 nephrotoxicity associated with cisplatin vs. non-cisplatin regimens was examined using inverse variance weighted fixed effects (FE) and random effects (RE) methods. Subgroup analyses of studies using SCr, GFR, and either SCr or GFR for screening were performed. Results: The literature search identified 2,359 studies, and 42 studies met all inclusion and exclusion criterion (N=9,521 patients). SCr was used as eligibility criteria in 20 studies (N=4,704), GFR was used by 9 studies (N=1,650), and either SCr or GFR was used by 13 studies (N=3,167). The overall RR for developing nephrotoxicity with cisplatin vs. non-cisplatin treatment was 1.75 (95%CI 1.18-2.58, p=0.005). Results from subgroup analyses showed the RR was 2.60 (95%CI 1.34-5.03, p=0.005) when SCr was used as eligibility criteria compared to 1.50 (95%CI 0.82-2.74, p=0.19) when GFR was used and 1.26 (95%CI 0.55-2.85, p=0.59) when either SCr or GFR was used. Results did not vary between FE and RE methods. Conclusions: Cisplatin based therapy is associated with a significant increase in severe nephrotoxicity. The risk of severe nephrotoxicity is higher in trials that utilize SCr as eligibility criteria compared to those that utilize GFR.

scholarly journals Vitamin K prophylaxis in newborns

2021 ◽  
Vol 21 (S1) ◽  
Author(s):  
Sophie Jullien
Keyword(s):  
Vitamin K ◽  
Literature Search ◽  
Randomized Trials ◽  
Supporting Evidence ◽  
Vitamin K Prophylaxis ◽  
Manual Search ◽  
Oral Regimen ◽  
Significant Difference ◽  
Haemorrhagic Disease ◽  
Key Terms

AbstractWe looked at existing recommendations and supporting evidence on the effectiveness of vitamin K given after birth in preventing the haemorrhagic disease of the newborn (HDN).We conducted a literature search up to the 10th of December 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.All newborns should receive vitamin K prophylaxis, as it has been proven that oral and intramuscular prophylactic vitamin K given after birth are effective for preventing classical HDN. There are no randomized trials looking at the efficacy of vitamin K supplement on late HDN. There are no randomized trials comparing the oral and intramuscular route of administration of prophylactic vitamin K in newborns. From older trials and surveillance data, it seems that there is no significant difference between the intramuscular and the oral regimens for preventing classical and late HDN, provided that the oral regimen is duly completed. Evidence assessing vitamin K prophylaxis in preterm infants is scarce.

scholarly journals Antiplatelets in patients with atrial fibrillation: a systematic review and meta-analysis of randomized clinical trials

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
A Benz ◽  
I Johansson ◽  
W Dewilde ◽  
RD Lopes ◽  
R Mehran ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Randomized Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
County Council ◽  
Qualitative Interaction

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr. Benz reports a personal research grant from the German Heart Foundation (Deutsche Herzstiftung e.V.). Dr. Johansson reports personal unrestricted research grants from Swedish Heart-Lung Foundation (Hjärt-Lungfonden) and from Stockholm County Council (Region Stockholm). Dr. McIntyre holds a fellowship award from the Canadian Institutes for Health Research (CIHR). Dr. Shoamanesh reports funding support from the Marta and Owen Boris Foundation and the Heart and Stroke Foundation of Canada. Background/Introduction: There is an ongoing controversy surrounding the efficacy and safety of antiplatelet agents in patients with atrial fibrillation (AF). Purpose We aimed to systematically assess the effects of antiplatelets on stroke and other outcomes in patients with AF, both receiving oral anticoagulation or not. Methods We searched MEDLINE, Embase and CENTRAL up until September 2020 to identify randomized trials allocating patients with AF to aspirin or a P2Y12 inhibitor, versus control. Where applicable, we obtained unpublished data from study authors. Random-effects models were applied for meta-analysis. Results Based on 21,518 patients from 18 randomized trials, there was no reduction in stroke with antiplatelet therapy (risk ratio [RR] 0.89, 95% confidence interval [CI] 0.76-1.04). There was a significant qualitative interaction according to whether patients were receiving concomitant oral anticoagulation or not (p < 0.001). Without concomitant anticoagulation, antiplatelets reduced stroke (RR 0.77, 95% CI 0.69-0.86), while they appeared to increase stroke with it (RR 1.33, 95% CI 0.98-1.79). A similar pattern emerged for ischaemic stroke. Antiplatelets increased major bleeding (RR 1.54, 95% CI 1.35-1.77) and intracranial haemorrhage (RR 1.64, 95% CI 1.20-2.24), and reduced myocardial infarction (RR 0.79, 95% CI 0.65-0.94), consistently and irrespective of concomitant anticoagulation. Antiplatelets had a neutral effect on mortality (RR 1.02, 95% CI 0.89-1.17). Conclusions Antiplatelet therapy did not reduce stroke and increased major bleeding in patients with AF. Antiplatelets did not affect mortality. Subgroup analysis suggests a reduction in stroke with antiplatelets in patients without concomitant oral anticoagulation, and a corresponding signal for harm in those with it. Abstract Figure.

scholarly journals COMT and Alpha-Tocopherol Effects in Cancer Prevention: Gene-Supplement Interactions in Two Randomized Clinical Trials

2019 ◽  
Vol 111 (7) ◽  
pp. 684-694 ◽  
Author(s):  
Kathryn T Hall ◽  
Julie E Buring ◽  
Kenneth J Mukamal ◽  
M Vinayaga Moorthy ◽  
Peter M Wayne ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Cancer Prevention ◽  
Randomized Trials ◽  
Randomized Clinical Trials ◽  
Statistical Tests ◽  
Meta Analysis ◽  
Alpha Tocopherol ◽  
Health Study ◽  
Post Trial

AbstractBackgroundVitamins are among the most frequently used supplements (48% of US adults). However, little is known about contributions of genetic variation to their efficacy and safety. Multiple pathways link catechol-O-methyltransferase (COMT) to the vitamin E supplement, alpha-tocopherol, and cancer.MethodsHere we determined if COMT exerted pharmacogenetic effects on cancer prevention in two randomized trials of alpha-tocopherol supplementation. Pharmacogenetic effects of common COMT rs4680 (val158met), which encodes a nonsynonymous valine-to-methionine substitution, were examined in the trial plus a 10-year post-trial follow-up (overall) period of The Women’s Genome Health Study (WGHS, N = 23 294), a 10-year alpha-tocopherol and aspirin trial with 10 years post-trial follow-up. Results were validated in a case/control (N = 2396/2235) subset of the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC, N = 29 133). The primary outcome was total cancers. Rates of cancer types prevalent in women (colorectal, breast, lung, uterine, and lymphoma/leukemia) were also examined. All statistical tests were two-sided.ResultsRandom-effects meta-analysis of rs4680 genotype strata, in WGHS and ATBC overall periods, revealed differential alpha-tocopherol effects compared with placebo: met/met (hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.80 to 0.97; P = .01), val/met (HR = 0.99; 95% CI = 0.92 to 1.06; P = .74), and val/val (HR = 1.18; 95% CI = 1.06 to 1.31; P = .002) with a statistically significant COMT by alpha-tocopherol interaction (Pinteraction <.001). Timing of effects differed, with stronger effects in WGHS trial and ATBC post-trial.ConclusionPharmacogenetic analysis of COMT and cancer prevention in two large randomized trials revealed statistically significant COMT by alpha-tocopherol interaction, such that alpha-tocopherol was beneficial among rs4680 met-allele (28.0%), but not val-allele (22.8%) homozygotes. These effects indicate the need for additional studies of genetic variation as a determinant of the benefits and possible harms of over-the-counter supplements, like alpha-tocopherol, used for health promotion.

Targeted therapies in the treatment of advanced pancreatic adenocarcinoma (PC): A systematic review and meta-analysis of randomized trials.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e15209-e15209
Author(s):  
Venessa T. Chin ◽  
Adnan Nagrial ◽  
Lorraine A. Chantrill ◽  
Katrin Marie Sjoquist ◽  
Chelsie O'Connor ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Adenocarcinoma ◽  
Targeted Therapies ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Advanced Pancreatic Adenocarcinoma

scholarly journals The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Hee Joong Lee ◽  
Tae Chul Park ◽  
Jae Hoon Kim ◽  
Errol Norwitz ◽  
Banghyun Lee
Keyword(s):  
Pregnant Women ◽  
Odds Ratio ◽  
Selection Criteria ◽  
Literature Search ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Control Group ◽  
Systematic Literature Search ◽  
Vaginal Progesterone ◽  
Threatened Abortion

Objective. To conduct systematic analyses to evaluate the efficacy of progesterone therapy for the prevention of miscarriages in pregnant women experiencing threatened abortion. Methods. In November 2016, we performed a systematic literature search and identified 51 articles in PubMed, Embase, and Cochrane databases. We identified nine randomized trials that included 913 pregnant women (including 322 treated with oral dydrogesterone, 213 treated with vaginal progesterone, and 378 control subjects) who met the selection criteria. Results. The incidence of miscarriage was significantly lower in the total progesterone group than in the control group (13.0% versus 21.7%; odds ratio, 0.53; 95% confidence interval (CI), 0.36 to 0.78; P=0.001; I2, 0%). Moreover, the incidence of miscarriage was significantly lower in the oral dydrogesterone group than in the control group (11.7% versus 22.6%; odds ratio, 0.43; 95% CI, 0.26 to 0.71; P=0.001; I2, 0%) and was lower in the vaginal progesterone group than in the control group, although this difference was nonsignificant (15.4% versus 20.3%; odds ratio, 0.72; 95% CI, 0.39 to 1.34; P=0.30; I2, 0%). However, the incidence of miscarriage was not different between the oral dydrogesterone and vaginal progesterone groups. Conclusion. Progesterone therapy, especially oral dydrogesterone, can effectively prevent miscarriage in pregnant women experiencing threatened abortion.

scholarly journals Endovascular thrombectomy without versus with intravenous thrombolysis in acute ischemic stroke: a non-inferiority meta-analysis of randomized clinical trials

2021 ◽  
pp. neurintsurg-2021-017667
Author(s):  
Chun-Hsien Lin ◽  
Jeffrey L Saver ◽  
Bruce Ovbiagele ◽  
Wen-Yi Huang ◽  
Meng Lee
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Randomized Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
Risk Difference ◽  
Endovascular Thrombectomy ◽  
Symptomatic Intracranial Hemorrhage

ObjectiveTo conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0–2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO).MethodsWe searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: −15%, −10%, −6.5%, −5%, and −1.3% for the risk difference for functional independence at 90 days.ResultsFour trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI −4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of −4% fell within the non-inferiority margins of −15%, −10%, −6.5%, and −5%, but not −1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI −3% to 5%) for mRS 0–1, and 1% (95% CI −1% to 3%) for symptomatic intracranial hemorrhage.ConclusionsThis meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.

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