Recombinant porcine factor VIII (rpFVIII) is indicated for treating bleeding episodes in acquired haemophilia A, but there are few data regarding laboratory methods to adequately monitor treatment. ...This study involving three Italian laboratories aimed to evaluate the analytical performance of different assays for measuring rpFVIII. Five spiked rpFVIII samples (0.5–1.5 IU/mL) were analysed on three days, in triplicate, with eleven combinations of reagents (Werfen, Boston, MA, USA: SynthasIL and SynthaFax for one-stage assay, Chromogenix Coamatic FVIII for chromogenic assay), FVIII depleted plasmas (with or without von Willebrand factor—VWF) and calibrators (HemosIL human calibrator plasma, porcine calibrator diluted in FVIII deficient plasma with or without VWF). The assays were performed on ACL TOP analysers (Werfen, Boston, MA, USA). Intra- and inter-assay and inter-laboratory Coefficient of Variation (CV%) were calculated together with percentage of recovery (% recovery) on the expected value. The results showed that the reagent combinations reaching satisfactory analytical performance are: SynthasIL/human calibrator/deficient plasma+VWF (total recovery 99.4%, inter-laboratory CV 4.04%), SynthasIL/porcine calibrator/deficient plasma+VWF (total recovery 111%, inter-laboratory CV 2.75%) and Chromogenic/ porcine calibrator/deficient plasma+VWF (total recovery 96.6%, inter-laboratory CV 8.32%). This study highlights that the use of porcine standard (when available) and FVIII deficient plasma with VWF should be recommended.
Describe the efficacy of a galenic glycopyrrolate formulation and its impact on patients with sialorrhea Quality of Life (QoL), including costs analysis.
We performed a retrospective observational ...study on 21 patients who received a custom-formulated galenic glycopyrrolate syrup for sialorrhea for an average period of 14.3 months. We analyzed the telephone interviews with elaborated and validated questionnaires and the therapy costs comparing the brand marketed drug with the galenic formulation.
Overall, 16 out of 21 patients (76.2%) reported a significant improvement in sialorrhea and QoL. In 14 subjects (66.7%), there was a remarkable decrease in the drooling severity; 10 individuals (47.6%) reported a reduction in drooling frequency. Nine patients experienced at least one adverse effect of glycopyrrolate therapy, and three of them stopped the treatment. No severe side effects were observed. The galenic drug significantly reduced costs for patients.
An oral glycopyrrolate solution easily administered to children with brain injuries is not commercially available in many European countries. This study demonstrates the efficacy of a compounded glycopyrrolate syrup on drooling severity, frequency and ensures a better QoL in patients and their caregivers.
Early T-cell reconstitution following allogeneic transplantation depends on the persistence and function of T cells that are adoptively transferred with the graft. Posttransplant cyclophosphamide ...(pt-Cy) effectively prevents alloreactive responses from unmanipulated grafts, but its effect on subsequent immune reconstitution remains undetermined. Here, we show that T memory stem cells (TSCM), which demonstrated superior reconstitution capacity in preclinical models, are the most abundant circulating T-cell population in the early days following haploidentical transplantation combined with pt-Cy and precede the expansion of effector cells. Transferred naive, but not TSCM or conventional memory cells preferentially survive cyclophosphamide, thus suggesting that posttransplant TSCM originate from naive precursors. Moreover, donor naive T cells specific for exogenous and self/tumor antigens persist in the host and contribute to peripheral reconstitution by differentiating into effectors. Similarly, pathogen-specific memory T cells generate detectable recall responses, but only in the presence of the cognate antigen. We thus define the cellular basis of T-cell reconstitution following pt-Cy at the antigen-specific level and propose to explore naive-derived TSCM in the clinical setting to overcome immunodeficiency. These trials were registered at www.clinicaltrials.gov as #NCT02049424 and #NCT02049580.
•TSCM are abundant early after allogeneic hematopoietic stem cell transplantation and derive from naive T cells that survived pt-Cy.•Pt-Cy allows the generation of donor primary and recall responses in transplanted patients, even in the presence of persistent antigen.
Introduction:
In the right ventricle, selective site pacing (SSP) has been shown to avoid detrimental hemodynamic effects induced by right ventricular apical pacing and, in the right atrium, to ...prevent the onset of atrial fibrillation and to slow down disease progression. The purpose of our multicenter observational study was to describe the use of a transvenous 4‐French catheter‐delivered lead for SSP in the clinical practice of a large number of centers.
Methods:
We enrolled 574 patients in whom an implantable device was indicated. In all patients, SSP was achieved by using the Select Secure System™ (Medtronic Inc., Minneapolis, MN, USA).
Results:
In 570 patients, the lead was successfully implanted. In 125 patients, atrial SSP was performed: in 75 (60%) the lead was placed in the interatrial septum, in 31 (25%) in the coronary sinus ostium, and in 19 (15%) in the Bachman bundle. Ventricular SSP was undertaken in 138 patients: in 105 (76%) the high septal right ventricular outflow tract (RVOT) position was paced, in seven (5%) the high free‐wall RVOT, in 25 (18%) the low septal RVOT, and in one (1%) the low free‐wall RVOT. In the remaining 307 patients, the His zone was paced: in 87 (28%) patients, direct His‐bundle pacing and in 220 (72%) patients para‐hisian pacing was achieved. Adequate pacing parameters and a lead‐related complication rate of 2.6% were recorded during a follow‐up of 20 ± 10 months.
Conclusions:
Our results demonstrated that many sites, in the right atrium, in the right ventricle, and in His‐bundle region, can be paced using the Select Secure System™. (PACE 2011; 34:339–347)
Introduction
The high morbidity and mortality associated with invasive fungal infections (IFIs) provide the rationale for antifungal prophylaxis in immuno-compromised pediatric patients undergoing ...hematopoietic stem cell transplantation (HSCT). Caspofungin and micafungin are antifungal agents of interest for prophylaxis of IFIs because of their potency against
Candida
and minimal toxicity or interactions with other drugs. Few studies have demonstrated the safety and efficacy of such echinocandins as prophylaxis for IFIs in patients undergoing HSCT.
Methods
This retrospective cohort study compared caspofungin and micafungin for prevention of IFIs in 93 pediatric patients undergoing HSCT for oncological or non-oncological disease. The observation began with the first dose of antifungal agent and ended 3 months after transplantation.
Results
Patients in the micafungin group had a higher overall treatment success rate of 87.2 versus 84.8% in the caspofungin group, but the difference was not significant. There were no statistically significant differences in the incidence or type of proven/probable IFIs between the 2 groups. The low incidence of death did not differ statistically between the groups. Patients in the caspofungin group presented more frequently with fever, during and after neutropenia. In both groups, we observed an expected worsening of blood chemistry parameters. There were no adverse events definitely attributable to the two antifungal agents.
Conclusion
These results demonstrate good efficacy and tolerability for caspofungin and micafungin. However, better results with respect to the incidence and resolution of fever in the micafungin group may suggest its use in preference to that of caspofungin.
Acute graft-versus-host disease (GvHD) remains the second leading cause of death, after disease relapse, in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The ...medical records of 112 pediatric patients who underwent allo-HSCT from matched unrelated and haploidentical donors were analyzed. Patients were divided into two groups, according to the GvHD prophylactic regimen used. In the control group, GvHD prophylaxis consisted of cyclosporine A (CsA) and methotrexate (MTX) or CsA and mycophenolate mofetil (MMF) at a standard daily dose of 30 mg/kg. All subjects in the study group received tacrolimus (FK506) and MMF. In this group, MMF was subjected to therapeutic drug monitoring (TDM) through mycophenolic acid (MPA) area under the curve AUC
. We found a statistically significant difference in both overall acute GvHD (
< 0.0001) and overall chronic GvHD (
< 0.05) incidence between the study and the control group. The initial daily MMF dose and the age at transplant in the study group proved to be inversely correlated (r = -0.523,
< 0.0001). The children under six years of age required a significantly higher daily MMF dose (
< 0.008). This study showed that pharmacological monitoring of MPA AUC
concentration allowed a reduction in the incidence of acute and chronic GvHD. MMF showed age-dependent pharmacokinetics due to greater drug clearance in younger children.
This study is to compare ibuprofen and ketorolac for children with trauma-related acute pain. We conducted a multicentre randomized, double-blind, controlled trial in the Paediatric Emergency ...Department setting. We enrolled patients aged 8 to 17 who accessed the emergency department for pain related to a limb trauma that occurred in the previous 48 h. At the admission, patients were classified based on numeric rating scale-11 (NRS-11) in moderate (NRS 4–6) and severe (NRS 7–10) pain groups. Each patient was randomized to receive either ibuprofen (10 mg/kg) or ketorolac (0.5 mg/kg) and the placebo of the not given drug in a double dummies design. NRS-11 was asked every 30 min until 2 h after drug and placebo administration. The primary outcome was NRS-11 reduction at 60 min. Among 125 patients with severe pain, NRS-11 reduction after 60 min from drug administration was 2.0 (IQR 1.0–4.0) for ibuprofen and 1.0 (IQR 1.0–3.0) for ketorolac (p = 0.36). Ibuprofen was significantly better, considering secondary outcomes, at 90 min with a lower median of NRS-11 (p 0.008), more patients with NRS-11 less than 4 (p 0.01) and a reduction of pain score of more than 3 NRS-11 points (p 0.01). Among 87 patients with moderate pain, the NRS-11 reduction after 60 min from drug administration was 1.63 (± 1.8) for ibuprofen and 1.8 (± 1.6) for ketorolac, with no statistically significant difference.
Conclusions
: Oral ibuprofen and ketorolac are similarly effective in children and adolescents with acute traumatic musculoskeletal pain.
Trial registration
: ClinicalTrial.gov registration number: NCT04133623.
What is Known:
• Limb trauma is one of the most common causes of paediatric emergency department visits. Non-steroidal anti-inflammatory drugs are the most frequently used analgesics in this clinical setting. In particular ibuprofen is the first over the counter non-steroidal anti-inflammatory drug in terms of use. Ketorolac is considered the most effective non-steroidal anti-inflammatory drug for severe pain.
What is New:
• This study directly compared oral ibuprofen and ketorolac for moderate and severe acute traumatic pain in children and adolescents. Both drugs were similarly effective in children and adolescents with severe pain, and ketorolac was not superior to Ibuprofen for moderate pain.
The health-related quality of life (HRQoL) of people with hemophilia (PWH) is an important issue, especially considering people suffering from chronic diseases beyond hemophilia. The principal aim of ...this study was to investigate the presence and relevance of psychological symptoms, both internalizing and externalizing, lifestyle, and HRQoL in a group of Italian PWH with chronic bloodborne co-infections and comorbidities. Furthermore, the research describes the association between psychological aspects and the impact of disease-related characteristics (type of hemophilia, presence of co-infections, and comorbidities) on them.
Seventy patients (mean age 46.77±11.3), 64 with severe hemophilia A (Factor VIII: C < 1 IU/dL) and 6 with severe hemophilia B (Factor IX <1 IU/dL), were consecutively recruited from seven Hemophilia Centers in Italy of Italian Association of Hemophilia Centers (AICE). In order to assess psychological symptoms, HRQoL, and lifestyle, three psychological questionnaires were administered (the SCL-90-R, SF-36, and PSQ, respectively).
A general decline in the quality of life and an increase in the tendency to adopt a lifestyle characterized by hyperactivity emerged. Inverse correlations were found between HRQoL and psychological distress. Although the SCL-90-R did not reveal symptoms above the clinical cut-off, co-infections significantly increased anxiety, depression, somatizations, paranoia, and social withdrawal. Lastly, HRQoL is impaired by co-infections as well as comorbidities.
Our preliminary results must be confirmed to deepen the findings between mental health and hemophilia.
To assess the effectiveness of sublingual ketorolac versus sublingual tramadol in reducing the pain associated with fracture or dislocation of extremities in children.
A double-blind, randomised, ...controlled, non-inferiority trial was conducted in the paediatric emergency department of a research institute. One hundred and thirty-one children aged 4-17 years with suspected bone fracture or dislocation were enrolled. Eligible children were randomised to ketorolac (0.5 mg/kg) and placebo, or to tramadol (2 mg/kg) and placebo by sublingual administration, using a double-dummy technique. Pain was assessed by the patients every 20 min, for a maximum period of 2 h, using the McGrath scale for patients up to 6 years of age, and the Visual Analogue Scale for those older than 6 years of age.
The mean pain scores fell significantly from eight to four and five in the ketorolac and tramadol groups, respectively, by 100 min (Wilcoxon sign rank test, p<0.001). The mean pain scores for ketorolac were lower than those for tramadol, but these differences were not significant at any time point (Mann-Whitney U Test, p values: 0-20 min: 0.167; 20-40 min: 0.314; 40-60 min: 0.223; 60-80 min: 0.348; 80-100 min: 0.166; 100-120 min: 0.08). The rescue dose of paracetamol-codeine was administered in 2/60 children in the ketorolac group versus 8/65 in the tramadol group (Fisher exact test, p=0.098). There were no statistically significant differences between the two groups in the frequency of adverse effects.
Both sublingual ketorolac and tramadol were equally effective for pain management in children with suspected fractures or dislocations.
The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ...ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1-6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20-0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1-6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis.
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