-
1.
Efficacy and safety of deferoxamine, deferasirox and deferiprone triple iron chelator combination therapy for transfusion-dependent β-thalassaemia with very high iron overload: a protocol for randomised controlled clinical trial
Premawardhena, A., Perera, C., Wijethilaka, M. N., Wanasinghe, S. K., Rajakaruna, Rhmg, Samarasinghe, Rankk, Williams, S., Mettananda, S.
BMJ open. 2024;14(2):e077342
Abstract
INTRODUCTION Despite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload. METHODS AND ANALYSIS This is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures. ETHICS AND DISSEMINATION Ethical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals. TRIAL REGISTRATION NUMBER The trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).
-
2.
High-dose intravenous immunoglobulin versus albumin 4% in paediatric toxic shock syndrome: a randomised controlled feasibility study
Portefaix, A., Dhelens, C., Recher, M., Cour-Andlauer, F., Naudin, J., Mortamet, G., Joram, N., Tissières, P., Ginhoux, T., Kassai, B., et al
Archives of disease in childhood. 2024
Abstract
PURPOSE Toxic shock syndrome (TSS) is a rare disease responsible for significant morbidity and mortality. Intravenous immunoglobulin (IG) therapy in paediatric TSS could improve shock and organ failure, but more consistent efficacy and safety data are needed. Our objective was to determine whether a randomised clinical trial (RCT) assessing intravenous IG in TSS in children is feasible. METHODS We performed a multicentre, feasibility, double-blind RCT assessing efficacy of high-dose intravenous IG versus albumin 4% (control group) within the first 12 hours of shock onset. Included patients were aged above 1 month and below 18 years with suspected TSS and septic shock. Feasibility was assessed by measuring inclusion rate, protocol compliance and missing data regarding death and the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score. Other secondary clinical outcomes were evaluated during hospital stay, at 60 day and 1 year. RESULTS 28 patients, admitted in 6 paediatric intensive care units during 36 consecutive months and followed for 1 year, received the allocated treatment: 13 in intravenous IG group, 15 in control group. The median age was 10.6 years and the sex ratio was 1. Inclusion rate was above 50%, protocol deviations were below 30% and missing data regarding death and PELOD-2 Score below 10%. No difference concerning secondary clinical outcomes between groups was observed, and more adverse events were reported in the control group. CONCLUSION It seems to be feasible to conduct an RCT assessing intravenous IG efficacy and safety in paediatric TSS but must be realised internationally, with choice of a clinically relevant endpoint and a specific design in order to be realistic. TRIAL REGISTRATION NUMBER NCT02219165.
-
3.
Two-dimensional radiographs and CBCT assessment of concentrated growth factor and platelet-rich fibrin scaffolds in regenerative endodontic treatment of immature incisors with periapical radiolucency: a randomized clinical trial
Elheeny, A. A. H., Tony, G. E.
Journal of endodontics. 2024
Abstract
INTRODUCTION The primary aim of this study was to compare the radiographic changes of immature incisors with periapical radiolucency after treatment with platelet-rich fibrin (PRF) and concentrated growth factor (CGF) platelet concentrate scaffolds as well as assessment of the clinical success rate over 12 months. The secondary aim was to monitor the radiographic changes in terms of reduction of periapical lesion diameter (PALD), root dentine thickness (RDT), root length (RL), and apical foramen width (AFW). The tertiary aim was to assess and pulp responses, after 12 months METHODS Fifty six children withseventy necrotic, single-rooted maxillary incisors with periapical radiolucency were treated with either CGF or PRF scaffolds (35 teeth per group). Two patients with four teeth (two teeth in each group) failed to attain the follow-up recalls. Radiographic changes in terms of reduction of periapical lesion diameter (PALD), root dentine thickness (RDT), root length (RL), and apical foramen width (AFW) were monitored using a two-dimensional radiograph and CBCT scan. The clinical performance of teeth receiving both scaffolds was assessed after 6 and 12 months. Categorical and continuous data were analyzed using the chi-square test and the t-test, respectively. The time and group effects on the means of different radiographic dimensions were tested using the general linear model (GLM). Bland-Altman plots were used to assess the level of agreement between the 2D radiographs and CBCT. The level of significance was defined at 0.05 and a 95% CI. RESULTS The means of PALD and RL showed significant enhancement in the CGF group compared to the PRF group (p< 0.05). While the difference between the two scaffolds in terms of RDT and AFW was not significant (p> .05). The findings of the 2D radiograph and CBCT were consistent. Clinically, both scaffold success rates were similar (93.9%) over the follow-up intervals. The influence of study independent variables had no significant effect on the success of the REPs outcome (p> 0.05). There was no significant difference in the positive pulp responses to the thermal and electric pulp tests after one year of treatment (p> 0.05). CONCLUSIONS According to the short-term follow-up, PRF and CGF were successful in treating immature teeth with periapical radiolucency by regenerative endodontics. Both scaffold systems induced periapical healing and root lengthening with significant superiority of CGF.
-
4.
Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial
Andre, M. C., Sanchez, C., Bressieux-Degueldre, S., Perez, M. H., Wütz, D., Blanchard-Rohner, G., Grazioli, S., Schöbi, N., Trück, J., Welzel, T., et al
EClinicalMedicine. 2024;67:102358
Abstract
BACKGROUND Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. METHODS This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). FINDINGS Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39). INTERPRETATION Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. FUNDING NOMIS, Vontobel, and Gaydoul Foundation.
-
5.
Immunomodulatory therapy in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS, MIS-C; RECOVERY): a randomised, controlled, open-label, platform trial
The Lancet. Child & adolescent health. 2024
Abstract
BACKGROUND Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS), also known as multisystem inflammatory syndrome in children (MIS-C) emerged in April, 2020. The paediatric comparisons within the RECOVERY trial aimed to assess the effect of intravenous immunoglobulin or corticosteroids compared with usual care on duration of hospital stay for children with PIMS-TS and to compare tocilizumab (anti-IL-6 receptor monoclonal antibody) or anakinra (anti-IL-1 receptor antagonist) with usual care for those with inflammation refractory to initial treatment. METHODS We did this randomised, controlled, open-label, platform trial in 51 hospitals in the UK. Eligible patients were younger than 18 years and had been admitted to hospital for PIMS-TS. In the first randomisation, patients were randomly assigned (1:1:1) to usual care (no additional treatments), usual care plus methylprednisolone (10mg/kg per day for 3 consecutive days), or usual care plus intravenous immunoglobulin (a single dose of 2 g/kg). If further anti-inflammatory treatment was considered necessary, children aged at least 1 year could be considered for a second randomisation, in which patients were randomly assigned (1:2:2) to usual care, intravenous tocilizumab (12 mg/kg in patients <30 kg; 8mg/kg in patients ≥30 kg, up to a maximum dose of 800 mg), or subcutaneous anakinra (2 mg/kg once per day in patients ≥10 kg). Randomisation was by use of a web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was duration of hospital stay. Analysis was by intention to treat. For treatments assessed in each randomisation, a single Bayesian framework assuming uninformative priors for treatment was used to jointly assess the efficacy of each intervention compared with usual care. The trial was registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS Between May 18, 2020, and Jan 20, 2022, 237 children with PIMS-TS were enrolled and included in the intention-to-treat analysis. Of the 214 patients who entered the first randomisation, 73 were assigned to receive intravenous immunoglobulin, 61 methylprednisolone, and 80 usual care. Of the 70 children who entered the second randomisation (including 23 who did not enter the first randomisation), 28 were assigned to receive tocilizumab, 14 anakinra, and 28 usual care. Mean age was 9·5 years (SD 3·8) in the randomisation and 9·6 years (3·6) in the second randomisation. 118 (55%) of 214 patients in the first randomisation and 39 (56%) of 70 patients in the second randomisation were male. 130 (55%) of 237 patients were Black, Asian, or minority ethnic, and 105 (44%) were White. Mean duration of hospital stay was 7·4 days (SD 0·4) in children assigned to intravenous immunoglobulin and 7·6 days (0·4) in children assigned to usual care (difference -0·1 days, 95% credible interval [CrI] -1·3 to 1·0; posterior probability 59%). Mean duration of hospital stay was 6·9 days (SD 0·5) in children assigned to methylprednisolone (difference from usual care -0·7 days, 95% CrI -1·9 to 0·6; posterior probability 87%). Mean duration of hospital stay was 6·6 days (SD 0·7) in children assigned to second-line tocilizumab and 9·9 days (0·9) in children assigned to usual care (difference -3·3 days, 95% CrI -5·6 to -1·0; posterior probability >99%). Mean duration of hospital stay was 8·5 days (SD 1·2) in children assigned to anakinra (difference from usual care -1·4 days, 95% CrI -4·3 to 1·8; posterior probability 84%). Two persistent coronary artery aneurysms were reported among patients assigned to usual care in the first randomisation. There were few cardiac arrythmias, bleeding, or thrombotic events in any group. Two children died; neither was considered related to study treatment. INTERPRETATION Moderate evidence suggests that, compared with usual care, first-line intravenous methylprednisolone reduces duration of hospital stay for children with PIMS-TS. Good evidence suggests that second-line tocilizumab reduces duration of hospital stay for children with inflammation refractory to initial treatment. Neither intravenous immunoglobulin nor anakinra had any effect on duration of hospital stay compared with usual care. FUNDING Medical Research Council and National Institute of Health Research.
-
6.
Clinical study on the role of platelet-rich plasma in human acellular dermal matrix with razor autologous skin graft repair of giant congenital pigmented nevus in children
Jin, F., Li, X., Chen, J., Liu, J., Wang, Y.
Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2024;90:305-314
Abstract
BACKGROUND NA OBJECTIVE Evaluate the safety and feasibility of platelet-rich plasma (PRP) in the treatment of giant congenital melanocytic nevi (GCMN) in children with human acellular dermal matrix (HADM) transplantation. PATIENTS AND METHODS A total of 22 children with GCMN were included in the study. They were divided into an experimental and a control group. The experimental group used the method of HADM with Razor Autologous Skin Graft combined with PRP to repair skin and soft tissue defects after giant nevus resection (Group A, n = 11). The control group was treated with HADM with Razor Autologous Skin Graft (Group B, n = 11) only. To compare the survival rate of skin grafts, we used the Vancouver Scar Scale (VSS) for the postoperative skin graft area and the Patient and Observer Scar Assessment Scale (POSAS) to compare the two groups of patients. RESULTS There was no statistically significant difference in age, gender, location of giant nevi, and pathological classification between Group A and Group (P > 0.05). The survival rate of skin grafting and the VSS and POSAS scores of scar tissue in group A were superior to those of group B (P < 0.05). CONCLUSIONS PRP has improved the survival rate of composite skin grafting in children with GCMN, and long-term satisfactory prognosis of scar healing. Therefore, we consider this treatment method a valuable contribution to clinical practice.
-
7.
Intravenous immunoglobulin in the management of neonatal sepsis: A randomised controlled trial
Rizvi MQ, Singh MV, Mishra N, Shrivastava A, Maurya M, Siddiqui SA
Tropical doctor. 2023;:494755221138689
Abstract
Sepsis is a leading cause of neonatal mortality and morbidity in low and middle-income countries. We designed a double-blinded randomised controlled trial in a neonatal intensive care unit (NICU) of a tertiary care teaching hospital to determine the role of intravenous immunoglobulin (IVIG) in decreasing hospital stay. Eighty neonates with clinical features of sepsis were enrolled in the study and placebo groups to receive 500 mg/kg of IVIG for three consecutive days or a placebo. The primary outcome measure was duration of hospital stay in days. The babies in both groups were comparable in terms of birth weight, gestation and sex distribution. There was no significant difference in duration of hospital stay (days) in the study and placebo groups. We found that treatment with IVIG did not shorten the duration of hospital stay in our setting.
-
8.
The Effect of Tranexamic Acid and Controlled Hypotension on Perioperative Blood Loss in Craniosynostosis Surgery
Moradi Farsani, D., Mazaheri, Z., Shafa, A.
Anesthesiology and pain medicine. 2023;13(1):e130462
Abstract
BACKGROUND Open cranial vault reconstruction is the standard technique of craniosynostosis correction that may cause significant blood loss. OBJECTIVES The current study aimed at comparing the effect of tranexamic acid (TXA), controlled hypotension, and their combination on perioperative blood loss and transfusion requirement in craniosynostosis surgery. METHODS The present randomized, double-blind clinical trial was conducted on 75 infants referred for craniosynostosis surgery during 2017 - 2018. Ten minutes before the start of surgery, 10 mg/kg of TXA was administered intravenously to patients in the first group (TXA group). In the second group, patients were subjected to the controlled hypotension anesthesia (CHA) using intravenous remifentanil 0.1 μ/kg (CHA group). In the third group, the patients underwent CHA similar to that of the second group, along with intravenous injection of 10 mg/kg of TXA (CHA-TXA group). Then, patients' mean arterial pressure (MAP), heart rate (HR), total blood loss, and transfusion volume were evaluated and recorded. RESULTS The results of the present study revealed that although the changes in MAP and HR parameters over time (three hours after surgery) were significant in all three groups, the lowest decrease was observed in the CHA-TXA group (P-value < 0.05). In addition, the total perioperative blood loss in the CHA-TXA group with the mean of 181.20 ± 82.71 cc was significantly less than the total perioperative blood loss in the CHA and TXA groups with the means of 262.00 ± 104.04 cc and 212.80 ± 80.75 cc, respectively (P-value < 0.05). Moreover, the transfusion volume in the CHA-TXA group with the mean of 112.40 ± 53.50 cc was significantly lower than the transfusion volume in the CHA and TXA groups with the means of 174.00 ± 73.93 cc and 160.63 ± 59.35 cc, respectively (P-value < 0.05). In contrast, the total blood loss and transfusion volume were not significantly different between the CHA and TXA groups (P-value > 0.05). CONCLUSIONS According to the results of the present study, although the administration of TXA alone could effectively prevent blood loss and was associated with fewer transfusion requirements, the combination of this approach with hypotensive anesthesia resulted in more reduction in perioperative blood loss and transfusion volume as well as better hemodynamic stability.
-
9.
Tranexamic acid in pediatric hemorrhagic trauma
Borgman, M. A., Nishijima, D. K.
The Journal of Trauma and Acute Care Surgery. 2023;94(1S Suppl 1):S36-s40
Abstract
There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma-induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown), which can be identified with viscohemostatic assays. Whether viscohemostatic assays can appropriately identify children who may benefit or be harmed by TXA is also unknown.
-
10.
Cut umbilical cord milking (C-UCM) as a mode of placental transfusion in non-vigorous preterm neonates: a randomized controlled trial
Bora, R. L., Bandyopadhyay, S., Saha, B., Mukherjee, S., Hazra, A.
European journal of pediatrics. 2023
Abstract
Routine practice of delayed cord clamping (DCC) is the standard of care in vigorous neonates. However there is no consensus on the recommended approach to placental transfusion in non-vigorous neonates. In this trial, we tried to examine the effect of cut umbilical cord milking (C-UCM) as compared to early cord clamping (ECC) on hematological and clinical hemodynamic parameters in non-vigorous preterm neonates of 30-35 weeks gestation. The primary outcome assessed was venous hematocrit (Hct) at 48 (± 4) hours of postnatal age. The important secondary outcomes assessed were serum ferritin at 6 weeks of age, mean blood pressure in the initial transitional phase along with important neonatal morbidities and potential complications. In this single centre randomized controlled trial, 134 non vigorous neonates of 30-35 weeks gestation were allocated in a 1:1 ratio to either C-UCM (n = 67) or ECC (n = 67). For statistical analysis, unpaired Student t and Chi square or Fisher's exact test were used. The mean Hct at 48 h was higher in the C-UCM group as compared to the control group, 50.24(4.200) vs 46.16(2.957), p < .0001. Also significantly higher was the mean Hct at 12 h, 6 weeks and mean serum ferritin at 6 weeks of age in the milked group (p < .0001). Mean blood pressure at 1 h and 6 h was also significantly higher in the milked arm. Need for transfusion and inotropes was less in the milked group but not statistically significant. No significant difference in potential complications was observed between the groups. Conclusion: C-UCM stabilizes initial blood pressure and results in higher hematocrit and improved iron stores. It can be an alternative to DCC in non-vigorous preterm neonates of 30-35 weeks' gestation. Further large multicentric studies are needed to fully establish its efficacy and safety. Trial registration: CTRI/2021/12/038606; registration date December 14, 2021. What is Known: • DCC is the routinely recommended method of placental transfusion for vigorous neonates but no consensus exist for neonates requiring resuscitation at birth. • C-UCM is easier to perform in non-vigorous neonates but there is paucity of studies in the preterm population. What is New: • C-UCM is effective as well as safe in non-vigorous preterm neonates of 30-35 weeks gestational age. • C-UCM holds promise as an alternative to DCC, especially in resource limited settings and in situations where the later is not feasible.