Background and ImportanceAmikacin is a widely used antibiotic in neonates. An adequate dosing regimen is essential for effective and safe therapy; however, many patients do not achieve adequate ...plasma concentrations due to high interindividual variability in this population.Aim and ObjectivesTo compare the amikacin plasma concentrations in neonates according to the administered 15mg/kg/24h dosing regimen (15-DR), a previously established protocol, versus the amikacin 12mg/kg/24h (12-DR) new protocol, with the aim of establishing best initial dosing regimen (DR) that guarantees an effective and safe treatment, as well as analysing differences between subpopulations (preterm or term).Material and MethodsRetrospective observational studyAll patients admitted to neonatal unit or neonatal intensive care unit under amikacin treatment and with 12-DR or 15-DR between January-July 2023 were included. Patients with different DR were excluded.The following variables were collected from the patients’ clinical histories (Orion Clínic®): gender, age, weight, preterm (<37 gestation weeks)/term, DR, minimum (Cmin) and maximum (Cmax) plasma concentrations. The optimal levels established were: Cmin <5 µg/mL and Cmax 20–30µg/mL.Quantitative variables are expressed as mean and standard deviation (SD) and qualitative variables as number and percentage (%). The Chi-square test was used to compare qualitative variables. Statistical significance was considered when p ≤ 0.05. Statistical analysis was performed with SPSS version 23.0.ResultsA total of 88 patients were identified, 11 were excluded because they were not neonates and 27 patients because they presented a different DR. Finally, 50 patients were included, 26 (52.0%) were male, mean age at level time was 7.6 (1.7) days, weight 2.9 (1.0) kg, and 35 (70.0%) were at term.Regarding treatment, 24 (48.0%) patients were treated with 12-DR and 26 (52.0%) with 15-DR. The mean Cmin was 1.4 (0.2) µg/mL and 2.3 (0.3), respectively, and mean Cmax was 26.0 (0.9) µg/mL for 12-DR group and 33.5 (1.3) µg/mL for 15-DR group. A total of 18 (75.0%) patients with 12-DR achieved target plasma concentrations compared to 7 (26.9%) in the 15-DR group, statistically significant differences were observed. When comparing between premature and term patients, no statistically significant differences were observed.Conclusion and RelevanceThis study demonstrates that amikacin 12mg/kg/24h dosing regimen guarantees better results in terms of optimal plasma concentrations in neonatal patients, which allows us to establish this dosage regimen as the initial dose in our patients. Clinical pharmacokinetics is essential for improving outcomes in neonates.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Background and ImportanceEvolocumab, an inhibitor of proprotein convertase subtilin-kexin type 9, represents an alternative therapeutic option for individuals who exhibit intolerance to standard ...low-density lipoprotein cholesterol (LDL-C) treatments or fail to attain desired LDL-C levels.Aim and ObjectivesThis study aims to assess the effectiveness, safety and adherence to evolocumab among patients with hypercholesterolemia.Material and MethodsObservational, retrospective, and multidisciplinary study that included patients who started treatment with evolocumab in a tertiary hospital between July 2016 and August 2022. Data variables (clinical history and dispensing program) were sex, age, indication, statins treatment, evolucumab dosage, treatment duration, LDL-C levels at baseline, 3, 6, 12 and 36 months, adverse effects (AEs) and adherence (medication possession rate). SPSS-27 statistical program (Wilcoxon test) was used to compare the decrease in LCL-C levels at different times.ResultsThe study enrolled 63 patients (52.4% women), with an average age at initiation of 61.8 (SD:11.1) years. The primary diagnoses included familial hypercholesterolemia (57.1%), established cardiovascular disease (33.3%) or both (9.5%). 63.5% of patients were intolerant to statins, 1.6% had contraindications, and 34.9% received statins at maximum tolerated doses without achieving target LDL-C levels. Dosage was 140 mg/14 days, with an average treatment duration of 3.0 (SD:1.6) years and an adherence rate of 91.3 (SD:14.9)%. The average LDL-C levels was 169.9 (SD:57.5)mg/dl, 84.9 (SD: 62.6) mg/dl, 77.2 (SD: 47.5)mg/dl, 75.7 (SD: 39.0) mg/dl and 84.0 (SD: 44.5) mg/dl at basal, 3, 6, 12 and 36 months, respectively. These LDL-C levels were significantly reduced (p<0.01) when compared to basal. Currently the majority (85.7%) of patients continue their treatment, 1.6% lost to follow-up, and 12.7% discontinued due to death (4.8%), AEs (6.3%) and lack of response (1.6%). Only four patients had AEs (headache; pseudo catarrhal symptoms, haematomas, spasms; anaphylaxis; skin reaction, diarrhoea and myopathies), and evolocumab was withdrawn in all of them.Conclusion and RelevanceEvolocumab emerges as a compelling therapeutic option for LDL-C reduction and cardiovascular risk mitigation, particularly for patients with statin intolerance or inadequate statin response. The results obtained in our real clinical practice (55.4% decrease in LDL-C levels at 12 months) were similar to those of the pivotal clinical trials. Further research is warranted to ascertain its impact on major cardiovascular events in real-world settings.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Background and ImportanceLung cancer (LC) is the third most common prevalent cancer and the leading cause of cancer-related death. Therapeutic options for LC are limited. A large number of ...immunotherapy-based clinical trials (CT) are underway due to their promising results. Therefore, it is necessary to evaluate the economic impact of CT in LC patients.Aim and ObjectivesTo evaluate the economic impact of participating in CT with immunotherapy provided by the sponsor in patients with LC.Material and MethodsSingle-centre multidisciplinary study calculating the cost-saving impact of the use of immunotherapy provided by the sponsor in CT in a tertiary hospital between January2019 and December2022.Inclusion criteriapatients diagnosed with LC (small cell and non-small cell) treated with commercialised immunotherapy in CT (amivantamab, atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab). Exclusion criteria: CT with placebo-masked immunotherapy.The information was retrieved from Farmis-Oncofarm®, pkEnsayos® and Orion-Logis®. Baseline characteristics (age and sex), diagnosis, clinical data (trials per phase and drug administered) and consumption data (quantity expressed in mg and costs avoided per CT, per patient and per diagnosis) were analysed.Statistical analysiscalculation of percentages and means with 95% confidence intervals (95%CI). Economic data was expressed in avoided costs.ResultsThe study included 81 patients (71.6% male) with an average age of 65.7 years (95%CI:63.8–67.6). Most of patients were diagnosed with non-small-cell LC (85.2%, n=69).A total of 27 CT were included (81.5% for non-small-cell and 18.5% for small-cell): phase I (n=1), phase I/II (n=2), phase II (n=6), phase IIa (n=1), phase III (n=12), phase IIIb (n=2), phase IIIb/IV (n=2) and phase IV (n=1). Nine of them used nivolumab (33.3%); 6 atezolizumab (22.2%); 6 pembrolizumab (22.2%); 3 durvalumab (11.1%); 2 ipilimumab (7.4%); 1 amivantamab (3.7%) and 1 avelumab (3.7%).The overall avoided cost was 2,178,167€ (1,715,360€ and 462,807€ for non-small cell lung cancer and small cell lung cancer, respectively), per CT 80,673€ and per patient 26,891€.Conclusion and RelevancePatient participation in CT with immunotherapy in LC has a great economic impact in terms of direct costs avoided in antineoplastic treatment. The inclusion of patients in these CT contributes to the sustainability of the healthcare system and allows patients access to innovative therapies.References and/or AcknowledgementsConflict of InterestNo conflict of interest.
Background and importanceGlycaemic alterations are highly prevalent in premature newborns during the first days of life. Particularly, hyperglycaemia has been reported as an independent risk factor ...for increased mortality and morbidity. This condition requires the use of insulin infusions for its treatment. However, this drug presents problems of adsorption to plastic that is intensified with low insulin concentrations and infusion rhythms used in neonates, conditioning the decrease and also the ignorance of the doses actually administrated to the newborn. There is no consensus on the appropriate insulin preparation and administration.Aim and objectivesTo determine the combination of variables for the preparation and administration of insulin infusions that provides higher accuracy and lower probability of error.Material and methodsAn experimental study was carried out with the aim of determining which variable (additive (albumin yes/no), solution (sodium chloride solution, NaCl 0.9%/glucose 5%), operator (1/2), preconditioning (yes/no), purge (yes/no), concentration (0.05–0.1 UI/mL), infusion rate (0.3–0.7 mL/h) and infusion duration (1 hour/24 hours)) most influences the concentration and dose of insulin administrated. The determinations were made with immunoassay using IMMULITE 1000 equipment. Previously, an ad hoc calibration was developed, adjusted to the range of doses commonly used in neonatal insulin infusions. Finally, a screening model using Plackett-Burman designs was developed to calculate insulin recovery and determine the variables with the most influence.Results24 experimental infusions were made, using combinations of different variables. After analysing the total of the samples, each of the recovery values obtained were entered in the screening model. The variables that achieved higher insulin recovery values were the additive (albumin - yes) and the solution (NaCl 0.9%). The model can explain 48.16% of the variation in insulin recovery, in which the additive has a standardised effect four times greater and the solution two times greater than the rest of the variables that do not exceed 1. (Figure 1: Pareto diagram)Conclusion and relevanceThe additive and the solution seem to be the most important determining factors for the recovery of insulin in the preparation of the infusions. The addition of albumin and preparing the infusions with sodium chloride solution 0.9% as solution results in a greater recovery of insulin.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and importanceHaemodynamically significant patent ductus arteriosus (hsPDA) is a common cause of morbidity and mortality in preterm infants. Currently, the first-line therapy for hsPDA is ...ibuprofen, but this treatment has potentially life-threatening side effects. Paracetamol has been proposed as an alternative to ibuprofen, but there is still insufficient clinical evidence to make a standard recommendation.Aim and objectivesTo evaluate the efficacy and safety of the standard treatment of hsPDA with ibuprofen versus paracetamol in the closure of hsPDA.Material and methodsNon-inferiority, randomised, multicentre, double-blind clinical trial was designed to evaluate the efficacy and safety of intravenous (IV) paracetamol versus IV ibuprofen in preterm patients with a gestational age (GA) ≤30 weeks diagnosed with hsPDA in four Spanish hospitals. Patients were randomized 1:1 to 10 mg/kg ibuprofen followed by 5 mg/kg at 24 and 48 hours or 15 mg/kg paracetamol every 6 hours for 3 days. If ductus size was >1 mm after the end of the 3-day course of the assigned treatment, another 3-day course of the same treatment was administered. If not, efficacy, ibuprofen and/or surgical closure were evaluated. The primary endpoint was ductus closure after the first treatment course.ResultsThe clinical trial is currently ongoing. The results presented correspond to an interim analysis with the objective of evaluating possible relevant safety warnings. A total of 91 patients have been recruited (approximately one-third of the scheduled recruitment). The populations of both groups have been comparable, with a mean GA of 26 weeks. For the main variable, ductus clousure after the first treatment course, an intention-to-treat analysis revealed no statistically significant differences between the groups (62.8% vs 42.2%, p=0.053). Applying the random stop method to assess the need to continue or stop the study, a p value <0.978 was obtained, the limit for assuming a lack of power. Likewise, no differences were found in the main safety variables.Conclusion and relevanceGiven the data obtained in the intermediate analysis, it is essential to continue with the planned recruitment. At the moment, with the results of this analysis and the previous literature, it is not yet possible to establish a clear recommendation on the use of paracetamol in hsPDA.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and importanceSARS-CoV-2 infection can impact the survival of patients with acute myeloid leukaemia (AML) but there is little published evidence in AML.Aim and objectivesTo analyse the ...clinical futures and outcome of SARS-CoV-2 infection in AML patients.Material and methodsAn observational multicentre study was conducted between March and May 2020 with 117 patients reported from 47 Spanish centres. Leukaemic and viral infections were studied, and inter-relationships were established.ResultsMedian age was 68 years, men (56.7% vs 43.3%), median time from AML diagnosis to SARS-CoV-2 was 4 months and mean number of comorbidities was 1.2. Cytogenetic risk was low in 16.9%, intermediate in 57.1% and high in 26.0%; 55.7% had active disease, 39.2% complete remission and 5.1% partial response. 29.4% were off-therapy and 70.6% were receiving anti-leukaemic treatment: induction chemotherapy (25.3%), hypomethylating (19.3%), clinical trial (17.0%), consolidation chemotherapy (14.8%), venetoclax (3.4%), FLT3 inhibitors (3.4%) and/or maintenance (1.1%). Overall, 3.7% were newly diagnosed, 77.8% had received one line of treatment, 14.8% two and 3.7% four. 15.4% had prior allogeneic transplantation.Only 4.0% of patients were asymptomatic, while the main signs and symptoms were fever (77.8%), pneumonia (75.0%), cough (65.3%), dyspnoea (52.0%), diarrhoea (20.4%), nausea/vomiting (12.2%), rhinorrhoea (10.2%) and headache (7.4%). Analytical parameters were: neutrophils 3112 cells/μL (1900–7300), lymphocytes 1090 cells/μL (1000–3000), interleukin 6 118 pg/mL (0–100), ferritin 4505 ng/mL (15–150) and D-dimer 2823 ng/mL (20–500), with liver enzymes altered in 23.9% of cases. 84.2% received specific treatment for coronavirus infection: chloroquine or hydroxychloroquine (82.2%), lopinavir/ritonavir (54.0%), corticosteroids (39.6%), azithromycin (33.0%), tocilizumab (15.8%), plasma convalescent (3.0%), clinical trial medication (3.0%), remdesivir (2.0%) and/or anakinra (1.0%).The course was mild in 14.7%, moderate in 32.0% and severe in 53.3%. Mean time to negativisation was 20.5 days, duration of symptoms 17.6 days and hospital stay 11.1 days. In 48.1% of cases treatment for AML was maintained, in 26.6% delayed and in 25.3% modified due to coronavirus disease. 47.5% died, establishing an association between mortality and age over 60 years (58.3% vs 36.4%, p=0.043), ≥2 lines of treatment (72.7% vs 44.3%, p=0.020), active disease (62.5% vs 29.4%, p=0.002) and pneumonia (61.2% vs 22.7%, p=0.002). Overall, 47.5% overcame the infection, and in 5.0% SARS-CoV-2 genetic material was still detected at the time of analysis. A non-significant lower mortality rate was observed among: previous transplantation (45.7% vs 64.3%, p=0.19), neutrophil >1900 cells/μL (41.1% vs 60.0%, p=0.09), lymphocyte >1000 cells/μL (42.9% vs 63.6%, p=0.09) and hydroxychloroquine or chloroquine plus azithromycin (35.3% vs 60.0%, p=0.10).Conclusion and relevanceSARS-CoV-2 infection produced high mortality among AML patients. Mortality was correlated with age, active disease and pneumonia.References and/or acknowledgementsAcknowledgements: Pethema FoundationConflict of interestNo conflict of interest
Background and importanceParenteral nutritional (PN) support in critically ill patients with SARS-CoV-2 infection is a currently unknown field of study with little published literature to generate ...scientific evidence.Aim and objectivesTo carry out a descriptive study of all patients with SARS-CoV-2 infection admitted to the ICU and resuscitation unit with invasive mechanical ventilation and central PN between March and June 2020 by the nutrition unit of the pharmacy service.Material and methodsA retrospective longitudinal study was carried out in a tertiary hospital. The clinical situation was reviewed, and the contributions of the artificial nutrition preparations were studied. Energetic requirements were calculated with the Harris–Benedict equation corrected for stress factor and protein requirements with weight adjusted by protein factor. Categorical variables are presented as percentages and continuous variables as mean (SD) or median (IQR).Results11 patients were included, with a mean age of 58.5±9.9 years, 72.7% men. 54.5% were admitted to the ICU and 45.5% to resuscitation, with a stay of 48±26 days and a mortality of 36.4%. The number of comorbidities was 3.1±1.9, highlighting arterial hypertension (63.6%), dyslipidaemia and diabetes mellitus (both 27.3%). All analytical parameters evaluated at admission were altered (IL-6, D-dimer, LDH, CRP and lymphocytes).BMI was 27.6±5.2 kg/m2, with 54.6% of patients with excess weight. Duration of PN was 6±3 days and in 81.8% enteral nutrition was co-administered by nasogastric tube. Estimated total energy expenditure was 2162±244 kcal/day with protein requirements of 117±14 g/day. With artificial nutritional support, 2166±427 kcal/day and 117±18 g protein/day were administered.PN provided 1169±256 kcal, 70±12 g protein, 129±31 g glucose and 39±16 g lipids. The non-protein energy/g nitrogen ratio was 77±14 kcal/g, the glucose:lipid ratio was 61:39±15%, volume was 1152±162 mL and osmolarity was 1425±111 mosmol/L. Regarding micronutrients, sodium (74 (IQR 32) mEq), potassium (59 (IQR 45) mEq), magnesium (10, (IQR 3) mEq), calcium (9 (IQR 0) mEq), chloride (48 (IQR 37) mEq) and phosphorus (12 (IQR 7) mmol) were included, in addition to mixtures of vitamins and trace elements.Conclusion and relevanceArtificial nutritional support was the only food source for intubated coronavirus infected patients, so it is essential that it meets nutritional requirements, as in this study, so that it contributes to the recovery of the patient.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and importanceRabbit antithymocyte immunoglobulin (ATG) is used to prevent or treat graft versus host disease (GVHD). There have been few studies on tolerance to administration of ATG in ...paediatric patients. It is related to immunomodulatory manifestations that cause an inflammatory response capable of triggering clinical and analytic manifestations similar to those of an infection, resulting in the administration of antibiotic in most patients.Aim and objectivesTo describe the tolerance to administration of ATG in paediatric patients who underwent bone marrow transplantation (BMT) and to analyse its relationship with clinical and analytic manifestations similar to an infection.Material and methodsThis was an observational retrospective study involving paediatric patients with BMT that received ATG (December 2010–February 2019). Variables collected were demographics (age/sex), BMT related variables (pathology, sources of haematopoietic stem cells (HSC), donor type), clinical symptoms (fever (secondary to ATG if 0–72 hours post-infusion), temperature), treatment (dose, premedication, side effects), analytics (maximum procalcitonin (PCT) and C reactive protein (CRP), liver and kidney function markers) and blood cultures. Variables were obtained from electronic/paper medical records and the oncohaematologic electronic prescribing programme.ResultsFifty-six patients were enrolled, 55.35% (31) men, with a median age of 7 years, and 92.8% (52) received ATG as prophylaxis and 7.2% (4) as refractory treatment of GVHD. The doses recorded were 1.25–2.5 mg/kg, with 2 mg/kg the most common dose (85.7%; 48) over 3 days (2 days if haploidentical BMT). All patients received premedication, full dose and no reduction in the rate of administration or discontinuation. The most frequent underlying diseases were oncological, mainly acute lymphoblastic leukaemia (57.1%; 32), and haematological (9 patients), mainly medullary aplasia (33.3%; 3). The main source of HSC was peripheral blood (50%; 28) and donor type was mismatched unrelated donor (39.28%; 22).In 73.2% (41) of patients, fever (38.5°C±0.5) appeared 11.28 hours after the start of infusion and lasted 1.77±0.84 days; 82.9% (34) of these patients received broad spectrum antibiotic treatment (mostly cefepime, amikacin, teicoplanin) over 7.61±3.79 days, with positive blood culture in 7.3% (3). Markers of infection were altered in most patients, with average values for CRP of 97.55±59.45 mg/dL and PCT of 35.57±28.55 ng/dL.Other side effects were hypertransaminasaemia (33.92%; 19), hyperbilirubinaemia (5.36%; 3), anaphylaxis (5.36%), capillary permeability syndrome (5.36%), alteration of renal function (1.78%; 1) and rash (1.78%).Conclusion and relevanceATG treatment in paediatric patients was associated with mild side effects. ATG triggered analytical and clinically altered parameters that simulated infection and hence empirical antibiotherapy was initiated which could be stopped precociously in the event of toxic fever by ATG.References and/or acknowledgementsNo conflict of interest.
Background and importanceApnoea of prematurity (AOP) is an alteration of the regulation of breathing and is very prevalent. The treatment of choice is caffeine but there is a lot of variability in ...its dosage, often using doses higher than recommended. Despite the wide safety range, pharmacokinetic monitoring may be necessary in certain cases.Aim and objectivesThe goal was to establish the usefulness of saliva for monitoring serum caffeine levels non-invasively.Material and methodsThis was a single centre, prospective, observational study. Premature patients admitted to the neonatology service between December 2017 and August 2018 being treated with caffeine for AOP were sequentially included on request for informed consent. Two paired samples of saliva–blood were collected per patient, at pre-dose time, taking advantage of routine blood withdrawals. Saliva was collected with cellulose sponges (Eyetec) in Eppendorf tubes and blood in dry tubes (Mini-collect). Salivary secretion stimulators were not used. The samples were centrifuged immediately after being collected and stored at −20°C. The determination was made by micro-extraction in solid phase in tube coupled to capillary liquid chromatography. We recorded date of birth, gestational age (GA), sex, weight, caffeine treatment regimen, renal function and concomitant drugs.ResultsForty-seven neonates were included, mean GA 27.8 (SD 2.36) weeks, birth weight 1.11±0.44 kg and 62% were male sex. Mean corrected GA on the day of determination was 31±2.7 weeks and weight was 1.85±0.45 kg. Administration was oral in 59% and intravenous in 41%. The mean concentration of caffeine in saliva was 16.35±9.21 and in serum 19.28±9.21 µg/mL. Serum and saliva concentrations showed a strong correlation (Pearson’s correlation=0.83, figure 1), which was higher with oral administration (0.90 vs 0.73 intravenous). Predictive model of linear regression of blood values was performed from saliva values. When comparing weight, GA, sex, caffeine dose (mg/kg) and concomitant drugs, no differences in correlation were observed through a multivariate analysis. No patient had kidney failure.Abstract 5PSQ-073 Figure 1Correlation between serum and saliva (intravenous and oral) levelsConclusion and relevanceSaliva determination is a reliable and non-invasive method for monitoring caffeine levels in preterm children with AOP. Correlation was higher when caffeine was administered orally, probably due to greater clinical stability when oral medication is administered.References and/or acknowledgementsNo conflict of interest.
Background and importancePatent ductus arteriosus (PDA) is a common cause of morbidity and mortality in preterm infants. The treatment of choice is ibuprofen but contraindications and serious adverse ...events limits its use. Paracetamol has been proposed as an alternative to ibuprofen, with good results (80–95% efficacy) and apparently less side effects.Aim and objectivesTo analyse the effectiveness and safety of intravenous paracetamol in the treatment of haemodynamically significant PDA (hsPDA).Material and methodsA retrospective cohort study of hospitalised infants was conducted in a level III neonatal intensive care unit between July 2013 and January 2019. Criteria inclusion: gestational age (GA) ≤30 weeks and treatment of hsPDA with paracetamol 15 mg/kg/6 hours (minimum 8 doses) after contraindication or ineffectiveness of ibuprofen. Closure was considered if the ductus was <1 mm and not significant. The need for post-paracetamol treatment was also analysed.ResultsFifty-four patients were included, with a median GA of 26±1.8 weeks and median birth weight of 853±293 g. In 14 patients, paracetamol was used as the first option and in 40 after ibuprofen (table 1). The overall closure rate was 37%. No adverse effects were reported during treatment.Abstract 4CPS-133 Table 1 Paracetamol First option Second option after ibuprofen Overall Reason Contraindication Overall Ineffectiveness Contraindication All Patients (n) 14 40 18 22 54 Closure (n) 7 13 3 10 20 Reopen (n) 2 3 0 3 5 No additional treatment required (n) 0 6 6 0 6 Additional treatment required (n) 7 21 10 11 28 Surgery (n) 1 16 9 7 17 Died (n) 7 5 0 5 12 Closure rate (%) 50.0 32.5 16.7 45.5 37.0 Closure rate+no additional treatment (%) 50.0 47.5 50.0 45.5 48.1 Closure rate (excluding deceased patients) (%) 71.4 34.3 16.7 52.9 40.5 Conclusion and relevanceOur efficacy results were much lower than those published in most studies and case series. In our series, the overall efficacy of paracetamol was 37.0% and 40.5% if deceased patients were excluded from the analysis.Well designed clinical trials are needed to help decide the role of paracetamol in the management of hsPDA as the results are very different depending on whether it is administered as the first choice (50.0% or 71.4% excluding the deceased) or after ibuprofen (32.4% or 34.3% excluding the deceased).References and/or acknowledgementsNo conflict of interest.
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