Abstract

Background and Objectives: To determine and compare the effects of the timing of oxytocin administration (routinely used for intraoperative uterotonic purposes in cesarean section (CS) deliveries in our clinic) on the severity of postpartum hemorrhage following CS. Materials and Methods: All study participants (n = 216) had previous cesarean deliveries, were 38-40 weeks pregnant, and had CS planned under elective conditions. The cases were randomly divided into two groups: one group (n = 108) receiving oxytocin administration before the removal of the placenta (AOBRP) and another group (n = 108) receiving oxytocin administration after the removal of the placenta (AOARP). In all cases, the placenta was removed using the manual traction method. The standard dose of oxytocin is administered as an intravenous (IV) push of 3 international units (IU); simultaneously, 10 IU of oxytocin is added to 1000 cc isotonic fluid and given as an IV infusion at a rate of 250 cc/h. All methods and procedures applied to both groups were identical, except for the timing of administration of the standard oxytocin dose. Age, body mass index (BMI), parity, gestational week, preoperative hemoglobin (HB) and hematocrit (HTC), postoperative 6th and 24th hour HB-HTC, intraoperative hemorrhage, additional uterotonic need during cesarean section, postoperative hemorrhage (number of pads), need for blood transfusion during or after cesarean section, cesarean section time, and postpartum newborn baby weight were evaluated. Results: Age (year), BMI (kg/m(2)), parity, gestational week, surgical time, and newborn weight (g) did not differ between the groups (p > 0.05). The AOBRP group had significantly higher postoperative 6th hour HB and HTC and postoperative 24th hour HB and HTC values (p < 0.05). The intraoperative hemorrhage level was higher in the AOARP group (p = 0.000). Conclusions: The administration of oxytocin before placenta removal did not change the volume of bleeding in the postoperative period but significantly reduced the volume of bleeding in the intraoperative period. Therefore, in the postoperative period, the HB and HTC values of the AOBRP group were higher than those of the AOARP group.

Abstract

BACKGROUND It has been shown that ferric carboxymaltose (FCM) improves symptoms and quality of life in iron-deficient patients with heart failure (HF). AIM: We aimed to systematically review studies conducted on the cost-effectiveness of FCM compared to placebo in iron-deficient patients with HF. METHOD We searched PubMed, EMBASE, Scopus, and Web of Science to find the relevant studies. After removing duplicates, two authors independently evaluated the titles, abstracts, and full texts. We included studies that investigated the full economic evaluations of FCM in HF patients with iron deficiency (cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis) and used the CHEERS tool to evaluate the quality of the studies. RESULTS Seven studies were included which evaluated the economic analysis of treatments with FCM in iron-deficient patients with HF. The CHEERS scores for most of the studies (n = 6) were 0.77 or higher (very good quality). The lowest incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) of FCM ($1801.96) was from Italy, and the highest ICER per QALY of FCM ($25,981.28) South Korea. Results of the studies showed that FCM, compared to placebo, was cost-effective in iron-deficient patients with HF. CONCLUSION FCM is a cost-effective treatment for iron-deficient patients with HF. Considering the fact that all the included studies in the present systematic review took place in high-income countries, we recommend further studies investigating the cost-effectiveness of FCM in low- and middle-income countries.

Abstract

Hydroxyurea and low dose thalidomide are low-cost, easily accessible Hb F inducing agents that have been found to decrease transfusion dependency among transfusion-dependent thalassemia patients. However, these drugs have not much been explored in a randomized controlled setting. The objective of this study was to determine the efficacy and safety of hydroxyurea and low dose thalidomide in adult transfusion dependent β thalassemia. A total of 39 transfusion dependent β thalassemia patients were randomized into three arms: Arm A (Hydroxyurea 500 mg/day), Arm B (thalidomide 50 mg/day), and Control Arm. The primary outcome was rise in haemoglobin at 24-weeks from the baseline levels. The mean age of the cohort was 26.9 ± 4.7 years. Total 13 patients (33.3%) were splenectomised. The mean rise of haemoglobin at the end of 24 weeks was 0.18 ± 0.645 g/dl, 0.56 ± 1.343 g/dl, and - 0.31 ± 0.942 g/dl in Arm A, Arm B and control arm, respectively, p = 0.127. The mean volume of blood transfused per unit body weight in 24 weeks was significantly less in the thalidomide arm compared with the control arm (p = 0.035). Abdominal pain (Grade 1-2, 23.1%) and pruritus (Grade 1, 15.4%) were the main adverse events in hydroxyurea arm, whereas somnolence was the main side effect noted in the thalidomide arm (Grade 1-2, 78.3%). Single agent hydroxyurea or thalidomide is ineffective in increasing haemoglobin and decreasing transfusion burden among majority of the adult transfusion dependent thalassemia patients. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s12288-022-01620-3.

Abstract

BACKGROUND Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use. OBJECTIVES To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDβT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDβT, quality of life and adverse events. MAIN RESULTS We included seven RCTs involving 291 people with NTDβT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF. AUTHORS' CONCLUSIONS We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDβT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.

Abstract

PURPOSE To evaluate the effects of shared decision-making (SDM) with patient decision aid (PtDA) on hemostasis device selection and reduction of decisional conflicts in patients undergoing transfemoral angiography. MATERIALS AND METHODS Patients undergoing angiography were randomized to receive either a standard explanation or the process aid of PtDA for choosing hemostasis devices. The decisional conflict was assessed using the 4-item SURE (Sure of myself; Understand information; Risk-benefit ratio; Encouragement) scale. Differences in demographic variables, clinical variables, and final choice of hemostasis devices were compared through univariable and multivariable logistic regression analyses. RESULTS In total, 158 patients were included-80 in the PtDA group and 78 in the standard group. No difference was found between the two groups in terms of patient demographic and clinical variables. The PtDA group scored better on all questions of the SURE scale both individually and collaboratively (P < .001). PtDA intervention (P = .031) and the reason for angiography (P = .0006) were the main variables that influenced patient hemostasis device choice in the univariable logistic regression analysis. Reason for angiography remained the only deciding factor that affected patient choice in multivariable logistic regression analysis (P = .015). CONCLUSIONS Step-by-step guidance and pictorial explanation with the assistance of PtDA led to improvements in patient knowledge but show no significant impact in multivariate analysis for the influence on the choice of hemostasis device. Implementation of PtDA-aided SDM is recommended for improving patient-centered care.

Abstract

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.

Abstract

Background There is a lack of evidence-based practice regarding the duration of pressure pack placement following tooth extraction. This study aimed to compare the incidence of post-extraction bleeding following 60 minutes versus 10 minutes of pressure pack placement. Methodology A randomized controlled trial was conducted at a tertiary care hospital and included patients requiring intra-alveolar tooth extractions. Patients were randomly allocated into the experimental group or control group by a permuted block randomization method. A blinded observer noted the incidence of post-extraction bleeding. Categorical variables were summarized as frequency and percentage. The chi-square test was used for intergroup statistical analysis. P-values <0.05 were considered statistically significant. Results There were 528 participants, 264 of whom were allocated to each group. The incidence of post-extraction bleeding was 8% and 6.8% in the experimental and control groups, respectively. On bivariate analysis, there was no statistically significant difference between the two groups (p = 0.618; relative risk with 95% confidence interval = 1.0). Conclusions In the majority of cases, hemostasis was achieved in 10 minutes. Therefore, removing the pressure pack after 10 minutes may be advised to ensure hemostasis and, ultimately, save chairside time.

Abstract

BACKGROUND Postoperative epistaxis is a known possibility following endoscopic sinonasal surgery. Tranexamic acid (TXA) has been shown to reduce intraoperative blood loss and improve the visual field. This study evaluates the clinical efficacy of TXA when given at end of surgery to reduce postoperative bleeding. METHODS This randomized, double-blinded placebo-controlled trial was conducted from April to November 2021. Patients scheduled to undergo endoscopic sinus or nasal surgery were randomized to receive an intravenous dose of 1g TXA or saline intraoperatively prior to extubation. A 10-inch visual analog scale (VAS) was used to query patients regarding postoperative bleeding each day for one week. The medical record was examined to determine the need for additional evaluations or interventions for epistaxis. RESULTS 40 patients completed the study. The mean/SD postoperative bleeding VAS for the TXA group on the day of surgery was not significantly different from the saline group (4.82 [2.18] in vs 5.03 [2.14] in, p = 0.8). There were no significant differences between treatment arms on any postoperative day through day 7 (0.67 [1.84] in vs 0.87 [0.99] in, p = 0.7), nor in the reduction in VAS compared to the respective baseline on the day of surgery. There were no significant differences in terms of additional interventions (e.g. additional evaluation in recovery, ED, or clinic, need for packing, or return to OR). CONCLUSION While TXA has previously demonstrated efficacy to reduce intraoperative bleeding during sinonasal surgery, when postoperative bleeding is already minimal at baseline, TXA does not appear to reduce it significantly further. This article is protected by copyright. All rights reserved.

Abstract

OBJECTIVES The aim of this review is to evaluate complications in patients undergoing surgical control of bleeding after thyroid surgery. Secondly, we have analyzed the rate of the main complications. METHODS The databases PubMed and EMBASE were searched for articles regarding complications after revision thyroid surgery for bleeding. A Systematic review methodology based on Preferred Reporting Items for Systematic Reviews and Meta-analysis was performed. RESULTS Nine studies met the inclusion criteria, six are retrospectives and three retrospectives controlled. The overall rate of bleeding after thyroid surgery was 1.38%. In these patients, the most common complication after revision surgery for bleeding is hypoparathyroidism 24.9% (95% CI: 20.7-29.5) followed by recurrent laryngeal nerve injury 8.1% (95% CI: 6.4-10.1) and wound infection 4.5% (95% CI: 2.5-7.6). Tracheostomy and other lethal complications are rarely described. CONCLUSION Although rare, complications after surgical control of bleeding in patients undergoing thyroid surgery can be serious. Therefore, in order to optimize the surgical outcomes, standardized protocol providing early detection and precise hemostasis procedure, is needed. Specific patient-informed consent for this condition should be created.

Abstract

AIMS: Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalisations and improved quality of life when used to treat ID at discharge in patients hospitalised for acute HF with left-ventricular ejection fraction of <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden. METHODS AND RESULTS The per country eligible population was calculated, aligning with the ESC 2021 HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalisation episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13,237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalisations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5,215 in Sweden to 205,630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within one year. CONCLUSIONS This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realised through implementation of the ESC HF guideline recommendations regarding ID treatment. This article is protected by copyright. All rights reserved.