Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial
IMPORTANCE The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear. OBJECTIVE To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy. DESIGN, SETTING, AND PARTICIPANTS Open-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019. INTERVENTIONS Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy. MAIN OUTCOMES AND MEASURES The primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome. RESULTS Among 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups. CONCLUSIONS AND RELEVANCE Among patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02648113.
Patients with myocardial infarction enrolled in the REALITY trial (n= 668).
Restrictive transfusion strategy, haemoglobin <8 g/dL (n= 342).
Liberal transfusion strategy, haemoglobin <10 g/dL (n = 324).
Among the patients in the restrictive transfusion group, 122 (35.7%) received transfusion, compared to 323 (99.7%) patients in the liberal transfusion group. At 30 days, major adverse cardiovascular events occurred in 36 patients (11.0%) in the restrictive group and in 45 patients (14.0%) in the liberal group. In the restrictive vs. liberal group, all-cause death occurred in 5.6% vs. 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs. 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs. 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups.
Clinical studies on platelet-rich plasma (PRP) therapy for chronic cutaneous ulcers: a systematic review and meta-analysis of randomized controlled trials
Advances in wound care. 2021
SIGNIFICANCE Platelet-rich plasma (PRP) may be a potential drug for treatment of chronic refractory ulcers, which increase the risk of systemic infection and local canceration. However, the efficacy and safety of clinical application of PRP are still controversial. Thus, this study was aimed to assess the efficacy and safety of PRP in patients with chronic ulcers. Recent Advances: For this meta-analysis, Cochrane's Library, MEDLINE, EMBASE, PubMed, and Web of Knowledge databases were searched. Results were pooled using a random-effects model. The primary outcome was the proportion of completely healed chronic ulcers. CRITICAL ISSUES Seventeen randomized controlled trials (RCTs) were included. Compared with the control group, PRP significantly increased the fraction of healed ulcers (pooled RR =1.50; 95% CI 1.20 to 1.87; I2=47.8%). In autologous PRP (APRP) and homologous PRP (HPRP) subgroups, there were statistical differences between the control group vs. treatment subgroup (pooled RR=1.30, 95% CI 1.10 to 1.54, I2=25.7%; pooled RR=3.53, 95% CI 1.94 to 6.43, I2=0.0%, respectively). In terms of percent of chronic ulcers area healed, there was a statistically significant difference between the PRP-treated group vs. the control group (SMD=1.37, 95%CI=0.91 to 1.82, I2=22.1 %). As for PRP safety, there existed a statistically significant difference between the APRP subgroup and the HPRP subgroup, respectively (pooled RR=0.58; 95% CI 0.35 to 0.98; I2=0.0%) and (pooled RR=4.12; 95% CI 1.55 to 10.96; I2=6.8%). FUTURE DIRECTIONS Our findings shows that PRP may be a beneficial treatment of chronic skin ulcers and that APRP may be much safer than HPRP.
Efficacy of topical tranexamic acid in epistaxis: A systematic review and meta-analysis
The American journal of emergency medicine. 2021;51:169-175
INTRODUCTION Epistaxis is a very common presentation in the emergency department (ED), accounting for approximately 1 in 200 ED visits in the United States. Currently, standard practice includes the initial use of topical anesthetics and vasoconstrictors, followed by more invasive treatments such as nasal packing, cauterization or surgical ligation for refractory cases. Over the years several studies have investigated the potential use of topical Tranexamic Acid (TXA) in the management of epistaxis. We have conducted a meta-analysis to assess the efficacy of topical TXA versus other standard practices or placebo in the management of epistaxis. METHODS PubMed and Scopus databases were searched from inception to April 2021. We included randomized controlled trials and observational studies investigating the efficacy of TXA in bleeding cessation in epistaxis in adults. The primary outcome measured was the prevalence of bleeding cessation after treatment at first assessment. Other outcomes were bleeding reoccurrence between 24 and 72 h and at 7-8 days. A random-effects model was used to estimate odds ratio (OR) for outcomes. RESULTS A total of eight studies were included in the analysis, including seven randomized trials and one retrospective study. We included a total of 1299 patients, 596 (46%) received TXA while 703 (54%) received control treatment (placebo, lidocaine plus vasoconstrictors or local anesthetics). Patients who were treated with TXA were 3.5 times (OR 3.5, 95% CI 1.3-9.7) more likely to achieve bleeding cessation at the first assessment. Patients treated with TXA had 63% (OR 0.37, 95% CI 0.20-0.66) less likelihood of returning due to rebleeding at 24-72 h. CONCLUSION Topical TXA is associated with better bleeding cessation rates after treatment compared to the standard practices.
Wound Healing in Diabetic Foot Ulcer Patients Using Combined Use of Platelet Rich Fibrin and Hyaluronic Acid, Platelet Rich Fibrin and Placebo: An Open Label, Randomized Controlled Trial
Acta medica Indonesiana. 2021;53(3):268-275
BACKGROUND Autologous platelet-rich fibrin (A-PRF) is an adjunctive method for diabetic foot ulcer (DFU) in addition to glycaemic control and debridement. This study aimed to evaluate the role of A-PRF + hyaluronic acid (HA), A-PRF and sodium chloride 0.9% (control) in DFU wound healing. Nowaday, the use of PRF autologous consider as adjuvant therapy in DFU treatment. METHODS This open-label randomized controlled trial was conducted at Koja District Hospital and Gatot Soebroto Hospital from July 2019 to April 2020. DFU patients with wound duration of three months, Wagner-2, and ulcer size < 40 cm2 were recruited and randomly assigned into A-PRF + AH, A-PRF and control group. On day-0, day-3 and day -7, samples and photographs were taken. Samples were analysed with ELISA and photographs were analysed with ImageJ to calculate granulation index (GI). Statistical analysis was performed using SPSS version 20. RESULTS Topical therapy with A-PRF + AH was associated with a significant increase in VEGF from day 0 (232.8 pg/mg) vs day 7 (544.5 pg/mg) compared to A-PRF on day 0 (185.7 pg/mg) vs day 7 (272.8 pg/mg), and the controls on day 0 (183.7 pg/mg) vs day 7 (167.4 pg/mg). On evaluation of VEGF swab, there is increasing significantly in A-PRF+HA group compare others group in day -3 ( p=0.022) and day -7 (p= 0.001).In the A-PRF + AH group, there was a significant decrease in IL-6 from day 0 (106.4 pg/mg) vs day 7 (88.7 pg/mg) compared with PRF on day 0 (91.9 pg/mg) vs day 7 (48,8 pg/mg). IL-6 was increased in the control group from day 0 (125.3 pg/mg) vs day 7 (167.9 pg/mg). On evaluation of IL-6 swab, there is decreasing significantly in A-PRF+HA group compare others group in day -7 (p= 0.041). CONCLUSION The PRF + HA combination increased angiogenesis and reduced inflammation in DFUs and may represent a new DFU therapy.
Supplementation with Iron in Pulmonary Arterial Hypertension: Two Randomized Crossover Trials
Annals of the American Thoracic Society. 2021
RATIONALE Iron deficiency, in the absence of anaemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin levels. The safety and benefit of parenteral iron replacement in this patient population is unclear. OBJECTIVES To evaluate the safety and efficacy of parenteral iron replacement in pulmonary arterial hypertension. METHODS In two randomised, double blind, placebo-controlled 12 week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject®) 1000 mg (or 15 mg/kg if weight < 66.7Kg) or saline as placebo and 17 patients in China received iron dextran (Cosmofer®) 20 mg iron/kg body weight or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by: a serum ferritin < 37 µg/l or iron < 10.3 µmol/l or transferrin saturations < 16.4%. RESULTS Both iron treatments were well tolerated and improved iron status. Analysed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6 minute walk test) or cardio-pulmonary haemodynamics, as assessed by right heart catheterisation, cardiac magnetic resonance or plasma NT-proBNP, at 12 weeks. CONCLUSION Iron repletion by administration of a slow release iron preparation as a single infusion to PAH patients with iron deficiency without overt anaemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with ClinicalTrials.gov (NCT01447628).
The high-risk bleeding category of different scores in patients with venous thromboembolism: Systematic review and meta-analysis
European journal of internal medicine. 2021
BACKGROUND In patients with venous thromboembolism (VTE), bleeding risk should be carefully assessed but none of the available risk scores is currently recommended. The aim of this study was to systematically evaluate the performance of bleeding scores in patients with VTE focusing on high-risk patients. METHODS Longitudinal studies were searched in Medline and Cochrane Library, as well as reviews and references of retrieved articles. Studies were identified, data were extracted, and reporting quality was evaluated. We determined the sensitivity, specificity, positive likelihood ratio (LR+), and diagnostic odds ratio (DOR) of the 'high risk' category of each bleeding score. Random effects meta-analysis was performed in order to derive the central estimates and 95% confidence intervals (95% CI). RESULTS Twenty-one studies and ten bleeding scores fulfilled the inclusion criteria. VTE-BLEED showed the highest sensitivity but the second-lowest specificity (Se 76%; Sp 61%), followed by ACCP (Se 59%; Sp 57%). The remaining scores had high specificity (> 80%) but a low sensitivity (< 20%). HEMORR(2)HAGES and Niewenhuis score showed the best performance regarding LR+ that was 2.67 and 5.91, respectively. Regarding DOR, the Niewenhuis score and VTE-BLEED were the best performers with 9.04; 95% CI 3.87-21.09 and 4.94 95% CI 2.66-9.09, respectively. In a cohort with patients predominantly treated with direct oral anticoagulants (DOACs), VTE-BLEED had the highest sensitivity (Se 77%; Sp 60%). CONCLUSIONS Overall, the majority of the risk scores showed a moderate ability to forecast major bleeding events, with the VTE-BLEED as the most sensitive in patients treated with DOACs.
Beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis
The Cochrane database of systematic reviews. 2021;1:Cd011973
BACKGROUND Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein thrombosis. Therefore, prevention is important. Band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding in children. However, primary prophylaxis is not the current standard of care in paediatric patients because it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children and adolescents. OBJECTIVES To determine the benefits and harms of beta-blockers compared with placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (April 2020). We screened the reference lists of the retrieved publications and manually searched the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstract books from 2008 to December 2019. We searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. SELECTION CRITERIA We planned to include randomised clinical trials, irrespective of blinding, language, or publication status to assess benefits and harms. We included observational studies, retrieved with the searches for randomised clinical trials, for a narrative report of harm. DATA COLLECTION AND ANALYSIS We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to asses risk of bias and use GRADE to assess the certainty of evidence. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and health-related quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to use intention-to-treat principle. We planned to analyse data with RevMan Analysis. MAIN RESULTS We found no randomised clinical trials that assessed beta-blockers compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We found four observational studies that reported on harms. As a systematic search for observational studies was not planned, we only listed the reported harms in a table. AUTHORS' CONCLUSIONS Randomised clinical trials assessing the benefits or harms of beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of beta-blockers versus placebo on patient-relevant clinical outcomes, such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of the two interventions.
Restrictive vs. Liberal Red Blood Cell Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: A Systematic Review and Meta-Analysis
Frontiers in cardiovascular medicine. 2021;8:736163
Objective: Anemia is frequent in patients with acute myocardial infarction (AMI), and the optimal red blood cell transfusion strategy for AMI patients with anemia is still controversial. We aimed to compare the efficacy of restrictive and liberal red cell transfusion strategies in AMI patients with anemia. Methods: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, and Clinicaltrials.gov, from their inception until March 2021. Studies designed to compare the efficacy between restrictive and liberal red blood cell transfusion strategies in patients with AMI were included. The primary outcome was all-cause mortality, including overall mortality, in-hospital or follow-up mortality. Risk ratios (RR) with 95% confidence intervals (CI) were presented and pooled by random-effects models. Results: The search yielded a total of 6,630 participants in six studies. A total of 2,008 patients received restrictive red blood cell transfusion while 4,622 patients were given liberal red blood cell transfusion. No difference was found in overall mortality and follow-up mortality between restrictive and liberal transfusion groups (RR = 1.07, 95% CI = 0.82-1.40, P = 0.62; RR = 0.89, 95% CI = 0.56-1.42, P = 0.62). However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion (RR = 1.22, 95% CI = 1.00-1.50, P = 0.05). No secondary outcomes, including follow-up reinfarction, stroke, and acute heart failure, differed significantly between the two groups. In addition, subgroup analysis showed no differences in overall mortality between the two groups based on sample size and design. Conclusion: Restrictive and liberal red blood cell transfusion have a similar effect on overall mortality and follow-up mortality in AMI patients with anemia. However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion. The findings suggest that transfusion strategy should be further evaluated in future studies.
Patients with acute myocardial infarction and anaemia (6 studies, n= 6,630).
Restrictive red blood cell transfusion strategy (n= 2,008).
Liberal red blood cell transfusion strategy (n= 4,622).
No difference was found in overall mortality and follow-up mortality between restrictive and liberal transfusion groups. However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion. No secondary outcomes, including follow-up reinfarction, stroke, and acute heart failure, differed significantly between the two groups. Subgroup analysis showed no differences in overall mortality between the two groups based on sample size and design.
Objective assessment of Platelet-Rich Plasma (PRP) potentiality in the treatment of Chronic leg Ulcer: RCT on 80 patients with Venous ulcer
Journal of cosmetic dermatology. 2021;20(10):3257-3263
BACKGROUND Chronic venous leg ulcer reduces the patients' activities and their overall quality of life. Platelet-rich plasma (PRP) was previously investigated as promising less invasive management for leg ulcers. THIS STUDY AIMS To re-assess the efficacy and safety of PRP in the management of chronic leg ulcers due to venous factors. PATIENTS/METHODS RCT enrolled 80 patients who clinically presented with chronic venous leg ulcers. Forty patients were allocated randomly for the treatment with autologous platelet-rich plasma (PRP). Intradermal and subdermal injection of PRP by 27guage syringe weekly, in all edges and in the granular floor of the ulcer for 4-6 sessions. Another 40 patients managed by conventional treatment by compression and dressing for the same period were allocated as Group B. Objective assessment achieved by the percentage of reduction of the size of the ulcer area, rate of healing, incidence of recurrence, and if side effects have been reported. RESULTS PRP therapy showed better results and high p value significance when compared to conventional therapy. CONCLUSION This study shows that PRP is effective and significant in promoting the wound healing process in chronic leg venous ulcers. PRP is simple, safe, and has a short learning curve technique.
The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study
European heart journal. 2021
AIMS: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. METHODS AND RESULTS The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. CONCLUSION In iron-deficient patients with HF and left ventricular ejection fraction ≤50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.