Abstract

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.

Abstract

BACKGROUND Venous ulcers (VU) are the most advanced stage of chronic venous disease (CVD) of the lower limbs. They are frequently associated with episodes of hemorrhage that can provoke chronic anemia (CA), delaying healing. There are no studies in the literature analyzing the prevalence of CA among patients with VU of the lower limbs and few studies have analyzed use of pentoxifylline to treat VU of the lower limbs. OBJECTIVES To evaluate the prevalence of CA in patients with lower limb VU and responses to treatment with ferrous sulfate (SF) compared with a combination of SF plus pentoxifylline as adjuvant treatment for VU of the lower limbs. METHODS A total of 67 patients with lower limb VU were recruited from a Lymphedema and Angiodysplasia Clinic at the Hospital das Clínicas, Recife, PE, Brazil. After initial clinical and laboratory assessments, patients diagnosed with CA were randomized into one of two groups: a control group, given SF (900 mg/day oral route), or a study group, treated with SF (900 mg/day oral route) and pentoxifylline (1,200 mg/day). All were reassessed after 90 days. RESULTS Twenty-seven patients (40%) had CA. After treatment, increases were observed in hemoglobin and hematocrit levels, iron kinetics had improved, and both depth and area of VU had reduced in both groups, without statistically significant differences. CONCLUSIONS A high prevalence of anemia was detected in the study population. The combination of SF and pentoxifylline was not more effective than SF alone for adjuvant treatment of VU of the lower limbs.

Abstract

AIMS: Iron deficiency is common in patients with heart failure (HF). In AFFIRM-AHF, ferric carboxymaltose (FCM) reduced the risk of hospitalisations for HF (HHF) and improved quality of life vs. placebo in iron-deficient patients with a recent episode of acute HF. The objective of this study was to estimate the cost-effectiveness of FCM compared with placebo in iron-deficient patients with left ventricular ejection fraction <50%, stabilised after an episode of acute HF, using data from the AFFIRM-AHF trial from Italian, UK, US and Swiss payer perspectives. METHODS AND RESULTS A lifetime Markov model was built to characterise outcomes in patients according to the AFFIRM-AHF trial. Health states were defined using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Subsequent HHF were incorporated using a negative binomial regression model with cardiovascular and all-cause mortality incorporated via parametric survival analysis. Direct healthcare costs (2020 GBP/USD/EUR/CHF) and utility values were sourced from published literature and AFFIRM-AHF. Modelled outcomes indicated that treatment with FCM was dominant (cost saving with additional health gains) in the UK, USA and Switzerland, and highly cost-effective in Italy [incremental cost-effectiveness ratio (ICER) EUR 1269 per quality-adjusted life-year (QALY)]. Results were driven by reduced costs for HHF events combined with QALY gains of 0.43-0.44, attributable to increased time in higher KCCQ states (representing better functional outcomes). Sensitivity and subgroup analyses demonstrated data robustness, with the ICER remaining dominant or highly cost-effective under a wide range of scenarios, including increasing treatment costs and various patient subgroups, despite a moderate increase in costs for de novo HF and smaller QALY gains for ischaemic aetiology. CONCLUSION Ferric carboxymaltose is estimated to be a highly cost-effective treatment across countries (Italy, UK, USA and Switzerland) representing different healthcare systems.

Abstract

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.

Abstract

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).

Abstract

BACKGROUND AND AIMS Diabetic foot ulcers (DFUs) are among challenging hurdles both for the patient and the physician. There is a recent trend toward finding novel and clinically efficient modalities to treat this potentially hazardous complication of diabetes mellitus in a timely manner. Herein, we aim to appraise the efficacy of platelet-rich plasma (PRP) in healing of clean DFUs. METHODS 90 patients with clean DFUs consisting of 56 (62.2%) males and 34 (37.8%) females with mean age (±standard deviation) of 56.52 (±7.14) years were enrolled in this study between June 2017 and December 2018. They were randomly allocated into control group (47 patients who received conventional dressing along with silver sulfadiazine ointment twice daily), and case group (43 patients who received PRP gel twice weekly for 3 weeks). All the patients were followed up for 6 months. RESULTS Our study showed that PRP significantly increased the healing rate of DFUs regardless of the age (p-value: 0.0), gender (p-value: 0.0), or smoking (p-value: 0.0) and blood pressure (p-value: 0.0) status of patients, but it did not have a significant impact on the need for amputation (p-value: 0.11), level of amputation (p-value: 0.16), or the need for further treatments such as graft or angioplasty (p-value: 0.52). CONCLUSION Regardless of the age, gender, or smoking and blood pressure status of patients, PRP can be efficiently used in diabetic patients to accelerate the healing rate of foot ulcers.

Abstract

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.

Abstract

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.

Abstract

STUDY OBJECTIVE Epistaxis is a common emergency department (ED) presentation and, if simple first aid measures fail, can lead to a need for anterior nasal packing. Tranexamic acid is an agent that contributes to blood clot stability. The aim of this study is to investigate the effectiveness of topical intranasal tranexamic acid in adult patients presenting to the ED with persistent epistaxis, and whether it reduces the need for anterior nasal packing. METHODS From May 5, 2017, to March 31, 2019, a double-blind, placebo-controlled, multicenter, 1:1, randomized controlled trial was conducted across 26 EDs in the United Kingdom. Participants with spontaneous epistaxis, persisting after simple first aid and the application of a topical vasoconstrictor, were randomly allocated to receive topical tranexamic acid or placebo. The primary outcome was the need for anterior nasal packing of any kind during the index ED attendance. Secondary outcome measures included hospital admission, need for blood transfusion, recurrent epistaxis, and any thrombotic events requiring any hospital reattendance within 1 week. RESULTS The study sample consisted of 496 participants with spontaneous epistaxis, persisting after simple first aid and application of a topical vasoconstrictor. In total, 211 participants (42.5%) received anterior nasal packing during the index ED attendance, including 111 of 254 (43.7%) in the tranexamic acid group versus 100 of 242 (41.3%) in the placebo group. The difference was not statistically significant (odds ratio 1.107; 95% confidence interval 0.769 to 1.594; P=.59). Furthermore, there were no statistically significant differences between tranexamic acid and placebo for any of the secondary outcome measures. CONCLUSION In patients presenting to an ED with atraumatic epistaxis that is uncontrolled with simple first aid measures, topical tranexamic acid applied in the bleeding nostril on a cotton wool dental roll is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing.

Abstract

OBJECTIVE The current study assesses the effects of platelet-rich plasma-fibrin glue (PRP-FG) dressing along with oral vitamin E and C on wound healing and biochemical markers in patients with non-healing diabetic foot ulcers (non-healing DFU). METHODS This randomized, double-blind, placebo-controlled trial was performed on twenty-five patients with non-healing DFU. Patients were treated with PRP-FG dressing plus oral vitamin E and C (intervention group) or PRP-FG dressing plus placebo (control group) for eight weeks. RESULTS Eight weeks after treatment, six wounds in the intervention group and two wounds in the control group were completely closed, and also wound size significantly reduced in both intervention (-9.7 ± 6.9 cm(2), p = 0.002), and control (-5.6 ± 5.4 cm(2), p = 0.003) groups. This reduction in wound size was significantly greater in the intervention group compared to the control group (p = 0.019). Also, a significant decrease in prooxidant-antioxidant balance (PAB) index, ESR, and hs-CRP were observed in the intervention group compared to the control group (p < 0.05). CONCLUSION Results of this trial showed that PRP-FG dressing along with oral vitamin E and C could be used to increase wound healing in patients with non-healing DFU by enhancing the wound healing process and reducing oxidative stress. TRIAL REGISTRATION This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04315909).