Bromocriptine for the treatment of postoperative cerebellar mutism syndrome in pediatric patients: Three case reports.

INTRODUCTION: Cerebellar mutism syndrome (CMS) is a common complication after posterior fossa tumor resection. It is characterized by a significant lack or loss of speech. Its biological origin remains unclear and there are no standardized treatments. However, bromocriptine seems to be a possible treatment for this condition. CASE REPORT: In this paper, we present three cases of pediatric patients (4, 5, and 17-year old) who developed CMS after posterior fossa tumor surgery. They were treated with bromocriptine to improve neurological symptoms.Management and outcome: Bromocriptine was started at a low dose and was progressively increased to reach the minimum effective dose. After four months of treatment, a normal and fluid speech was observed in the three patients. No discontinuation due to adverse events were reported. DISCUSSION: Bromocriptine has shown to be an effective and safe treatment for CMS in pediatric patients after posterior fossa tumor resection.

Effectiveness and Safety of Ombitasvir-Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin for HCV Genotype 1 Infection for 12 Weeks Under Routine Clinical Practice.

BACKGROUND: No previous studies exist examining the effectiveness and safety in real clinical practice of the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV). OBJECTIVE: To evaluate the effectiveness and safety in real clinical practice of the combination of OBV/PTV/r+DSV with or without ribavirin for 12 weeks in treatment-naïve and previously treated adult patients with chronic hepatitis C virus (HCV) genotype 1 infection. METHODS: This was an observational study of a prospective cohort of treatment-naïve and pretreated adult patients who received 12 weeks of OBV/PTV/r (25/150/100 mg once daily) and DSV (250 mg twice daily) with or without ribavirin. The primary effectiveness outcome was sustained virological response 12 weeks after the end of treatment (SVR12). Safety outcomes were presented by the incidence of adverse events. RESULTS: A total of 116 of 121 patients achieved a SVR12 (95.9%, 95% CI = 90.6-98.6). The SVR12 rate was 93.8% (95% CI = 86.0-97.9) in cirrhotic patients and 100% (95% CI = 91.4-100.0) in noncirrhotic patients. Adverse events occurred in 91.7% of patients, of which 81.8% were grade 1/2, and none led to premature discontinuation. Grade 3 adverse events were reported in 9.9% of patients. The most frequent adverse event was anemia (52.1%), although only 1.6% had a hemoglobin level below 8 g/dL. The incidence of any adverse event was higher in the group of patients who received ribavirin (96.5% vs 80.0%, P = 0.002). CONCLUSIONS: The combination of OBV/PTV/r+DSV with or without ribavirin for 12-week settings achieved a high rate of SVR12, with an acceptable safety profile in routine clinical care.

Prevention and treatment of intraluminal catheter thrombosis in children hospitalised in a paediatric intensive care unit.

AIM: The aim of the study was to develop and implement a protocol for the prevention and treatment of catheter related intraluminal thrombosis in a paediatric intensive care unit METHODS: A computerised search was carried out on MEDLINE, through PubMed, using the medical subject heading 'central venous catheter', 'central venous access device', 'central venous line' associated with 'occlusion', 'obstruction', 'catheter-related thrombosis', 'critically ill patients' and 'thrombolytic therapy'. References of reviewed articles were also searched for relevant titles as well as non-randomised controlled trials and series of cases when no information of higher level of evidence was available. RESULTS: With the information gathered, a protocol for the prevention and treatment of catheter related intraluminal thrombosis was elaborated and those recommendations that best suit our environment were included. They were agreed upon by a broad panel of professionals working in the Pediatric Intensive Care Unit and the Pharmacy Department. CONCLUSIONS: Due to the variety of options available for the pharmacotherapeutic management of intraluminal catheter thrombosis, one measure to improve the quality of the therapy and to diminish the variability in the prescription could be the implementation of a protocol as described in this paper.

Risks in the implementation and use of smart pumps in a pediatric intensive care unit: application of the failure mode and effects analysis.

OBJECTIVES: The aim of this study was to identify risk points in the different stages of the smart infusion pump implementation process to prioritize improvement measures. METHODS: Failure modes and effects analysis (FMEA) in the pediatric intensive care unit (PICU) of a General and Teaching Hospital. A multidisciplinary team was comprised of two intensive care pediatricians, two clinical pharmacists and the PICU nurse manager. FMEA was carried out before implementing CareFusion infusion smart pumps and eighteen months after to identify risk points during three different stages of the implementation process: creating a drug library; using the technology during clinical practice and analyzing the data stored using Guardrails® CQI v4.1 Event Reporter software. RESULTS: Several actions for improvement were taken. These included carrying out periodical reviews of the drug library, developing support documents, and including a training profile in the system so that alarms set off by real programming errors could be distinguished from those caused by incorrect use of the system. Eighteen months after the implementation, these measures had helped to reduce the likelihood of each risk point occurring and increase the likelihood of their detection. CONCLUSIONS: Carrying out an FMEA made it possible to detect risk points in the use of smart pumps, take action to improve the tool, and adapt it to the PICU. Providing user training and support tools and continuously monitoring results helped to improve the usefulness of the drug library, increased users' compliance with the drug library, and decreased the number of unnecessary alarms.

Pharmacokinetics of eculizumab in adult and pediatric patients with atypical hemolytic uremic syndrome and C3 glomerulopathy. / Farmacocinética de eculizumab en pacientes adultos y pediátricos con síndrome hemolítico urémico atípico y glomerulopatía C3.

OBJECTIVE: The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy. METHODS: Observational, ambispective and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in five hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre-dose and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations. RESULTS: Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (IQR 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined. Mean pre-dose and post-dose concentration values detected during the maintenance phase were 243.8 (SD 240.6) µg/mL and 747.4 (SD 444.3) µg/mL, respectively. Increased complement blockade was observed at higher pre-dose concentrations (p=0.002) and decreased serum creatinine at both higher pre- and post-dose concentrations (p=0.001 and p=0.017, respectively). Using ROC curves, it was determined that a pre-dose concentration >149.0 µg/mL was optimal to achieve complement blockade, with an AUC of 0.87 (0.78-0.95). Finally, high inter-individual (48.9% CV) with low intra-individual variabilities (11.9% CV) in eculizumab clearance were observed. CONCLUSIONS: The present study reports supratherapeutic concentrations of eculizumab in patients with aHUS, and defines higher concentrations than those described in the data sheet to achieve blockade, thus encouraging the personalization of treatment with eculizumab.

[Translated article] Pharmacokinetics of eculizumab in adult and pediatric patients with atypical hemolytic uremic syndrome and C3 glomerulopathy.

OBJECTIVE: The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy. METHODS: Observational, ambispective, and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in 5 hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre- and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations. RESULTS: Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (interquartile range (IQR) 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined. Mean pre- and post-dose concentration values detected during the maintenance phase were 243.8 (SD 240.6) µg/mL and 747.4 (standard deviation (SD) 444.3) µg/mL, respectively. Increased complement blockade was observed at higher pre-dose concentrations (P = .002) and decreased serum creatinine at both higher pre- and post-dose concentrations (P = .001 and P = .017, respectively). Using ROC curves, it was determined that a pre-dose concentration >149.0 µg/mL was optimal to achieve complement blockade, with an AUC of 0.87 (0.78-0.95). Finally, high inter-individual (48.9% variation coefficient (CV)) with low intra-individual variabilities (11.9% CV) in eculizumab clearance were observed. CONCLUSIONS: The present study reports supratherapeutic concentrations of eculizumab in patients with aHUS, and defines higher concentrations than those described in the data sheet to achieve blockade, thus encouraging the personalization of treatment with eculizumab.

Use of Monoclonal Antibodies in a Pediatric Patient With Severe Combined Immunodeficiency and Persistent SARS-CoV-2 Infection.

We describe the use of monoclonal antibodies for the treatment of persistent SARS-CoV-2 infection in a pediatric patient with severe combined immunodeficiency who required urgent stem cell transplantation to cure his disease.

Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice.

BACKGROUND: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. METHODS: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. RESULTS: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. CONCLUSION: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.

Prescribing errors intercepted by clinical pharmacists in paediatrics and obstetrics in a tertiary hospital in Spain.

PURPOSE: To assess the main differences in clinical significance of the prescribing errors intercepted by clinical pharmacists in paediatrics and obstetrics and the reasons for these prescribing errors, as well as the differences in pharmacists' activity indicators. METHODS: The was a cross-sectional epidemiological study analysing the activities of paediatric pharmacists in a maternity and children's hospital with 180 paediatric beds and 138 obstetrics and gynaecology beds between January 2007 and December 2009. The following variables were analysed: clinical significance of prescribing errors intercepted, reason for the error, impact of the intervention by pharmacist, acceptance rate of the recommendation made, medication involved, intervention detection date and observations. RESULTS: A total of 2,449 interventions in medical orders were recorded. Interventions that were not accepted by doctors were excluded, leaving 43 cases (2.1%) of extremely significant interventions and 170 (8.4%) very significant interventions. Interventions in what were deemed to be error-free situations were excluded. Significance testing (based on 2,035 errors detected) showed that 1.7% of the detected errors were potentially lethal (35 cases), while 10.2% (210 cases) were clinically serious. The main reason for the interventions was the detection of a dosage between 1.5- and tenfold higher than the recommended dosage. The overall rate of acceptance of the pharmacist's suggestions was 92.2%. Pharmacists carried out an average of 0.016 interventions/patient-day throughout the study period. CONCLUSIONS: Paediatric patients had a fourfold higher risk of serious errors than the maternity population. Pharmacist intervention had a major impact on reducing prescribing errors in the study period, thus improving the quality and efficiency of care provided.

Treatment and prophylaxis of catheter-related thromboembolic events in children.

PURPOSE: The therapeutic management of catheter-related thromboembolic events in children is still a challenge due to the large number of potentially effective pharmacological alternatives and the insufficient scientific evidence available. A bibliographic review was performed in order to identify the available pharmacological alternatives for the prophylaxis and therapeutic management of catheter-related thrombosis in children. METHODS: A literature search was carried out on MEDLINE using the medical subject heading (MeSH) central venous catheter thrombosis and on Google Scholar. The search was limited to review papers, meta-analyses, clinical practice guidelines, and randomized controlled trials performed on pediatric populations until November 2011. RESULTS: The different options for anticoagulation include unfractionated heparin, low molecular weight heparin and vitamin K antagonists. Thrombus resolution is stimulated more rapidly with thrombolytic agents than with anticoagulants, but the risk-benefit ratio must be considered. Streptokinase is not considered an optimal alternative due to the risk of anaphylactic reactions and has been replaced by urokinase, alteplase or the newer reteplase. Preventive strategies have been considered and most centers have protocols for routine flushing of the catheter with heparin or normal saline. Intraluminal application of urokinase and alteplase has also been studied. CONCLUSIONS: The wide range of options available for the pharmacotherapeutic management of catheter-related thromboembolism in children and the lack of strong evidence on the comparative efficacy and safety of the different therapeutic options, make its positioning rather difficult. Randomized controlled trials and national plans should be set up urgently.

Standardisation of intravenous infusion therapy for paediatrics: big challenges for the little patients.

BACKGROUND: Worldwide organisations advocate standardising the management of intravenous drugs as an essential strategy to increase safety in paediatric healthcare settings. Intravenous administration is a route associated with some potential complications. Many adverse events are related to the use of intravenous medications, and the great variability in their handling and preparation represents an added risk that jeopardises the safety of children. PURPOSE: To standardise the dilutions of intravenous drugs most commonly administered to Spanish hospitalised paediatric and neonatal patients. METHODS: The process leading to the standardisation of concentrations was undertaken following a two-round modified Delphi procedure. The consensus included the most common drugs administered by continuous or intermittent intravenous infusion to hospitalised and/or critically ill paediatric patients. RESULTS: For paediatric patients, the proposal included a total of 102 drugs (45 continuous infusion and 59 intermittent infusion), with 192 concentrations to be standardised. The final consensus included 101 drugs (99%), of which 44 were continuous infusion and 59 intermittent infusion; 160 concentrations were standardised (72.7%). For neonates, the initial proposal included 80 drugs (38 continuous infusion and 43 intermittent infusion), with 189 concentrations to be standardised. The final consensus included 80 drugs (100%), of which 38 were continuous infusion and 43 were intermittent infusion; 120 concentrations were standardised (49.2%). CONCLUSIONS: This proposal showed that standardisation is a feasible approach that can be reached by other healthcare institutions. It can be used in other centres and contribute in the future to unifying paediatric clinical practice.

Adecuacy of pediatric antimicrobial prescribing in the Emergency Department at discharge.

INTRODUCTION: In January 2019, the Community of Madrid's Health Department published a guide about the use of antimicrobials in outpatient children. Taking this regional Guide as reference, this study was aimed at estimating the adequacy of the antimicrobial stewardship at discharge from a pediatric Emergency Department (ED). Secondarily, the differences in adequacy according to the diagnosis and the prescriber were studied, and the agreement between this Guide and the protocols of the ED was assessed. MATERIAL AND METHODS: An observational, descriptive, retrospective study was conducted on patients under 16 years old, with a diagnosis included in the regional Guide who were discharged from a pediatric ED between March of 2018 and February of 2019. Prescription was considered adequate when the indication, the antibiotic and the posology (dosage, dosing interval, length of treatment and route of administration) were correct. RESULTS: 165 out of 648 (25,5%) infectious diseases processes analyzed received antimicrobial treatment. In 23 processes treated with antimicrobial, the adequacy could not be evaluated due to the absence of data necessary to assess any aspect of posology. Therapy was considered appropriate in 550/625 processes (88.0%). When antimicrobial treatment was prescribed, 70/142 (49.3%) were appropriate and no statistically significant differences in adequacy were found between prescribers. Posology was the worst handled point of the prescription (26.3%). Tract urinary infection, conjunctivitis and otitis media were the pathologies with the lowest adecuacy (44.4%; 50.0% and 52.2%) and presented the highest discrepancy between the Guide and the center protocols (κ = 0.308; κ = 0.000; κ = 0.586). CONCLUSIONS: The adequacy of the management of infectious processes to the reference Guide in our pediatric ED was high, but it was below 50% when antimicrobial treatment was required. The degree of adequacy to the local protocols of the center was greater than to the regional Guide. This reveals a discrepancy between the 2 documents that should be analyzed and corrected according to the available scientific evidence.

Multicenter randomized clinical trial comparing dexamethasone versus placebo in preventing upper airway obstruction after extubation in critically ill children.

To analyze the effectiveness of dexamethasone in preventing upper airway obstruction (UAO) symptoms after extubation and the need of reintubation in critically ill children. Multicenter, prospective, double-blind, randomized, phase IV clinical trial involving five pediatric intensive care units. Children between 1 month and 16 years-of-age intubated for more than 48 h were included. Patients were randomized to receive placebo or dexamethasone 0.25 mg/kg every 6 h, 6-to-12 h prior to extubation (four doses). 48 h follow-up was carried out after extubation. Severity of UAO symptoms (Taussig score, stridor) and reintubation requirement were compared. 147 patients were randomized (10 were excluded), 70 patients received dexamethasone and 67 placebo. No global differences were found in the presence of stridor or moderate-to-severe UAO symptoms (Taussig ≥ 5), but Taussig ≥ 5 was less frequent in patients less than 2 years-of-age treated with steroids (p = 0.014). Median Taussig score was lower in the dexamethasone group 1 h after extubation, p < 0.001. 27 patients required reintubation, 9 due to UAO: 3 (4.3%) in the dexamethasone group and 6 (8.9%) in the placebo group, p = 0.319. In those intubated > 5 days, reintubation due to UAO was higher in the placebo group (2.4% vs. 14.3, p = 0.052). Nebulized epinephrine and budesonide were required more frequently in the placebo group in the first 2 h (p = 0.041) and 1 h (p = 0.02) after extubation, respectively. No relevant side effects were observed. Dexamethasone prior to extubation did not significantly reduce moderate-severe UAO symptoms, except for patients under 2-years of age. Dexamethasone could decrease Taussig score and the need of rescue therapies, as well as reintubation rates in those intubated for more than 5 days.

Antimicrobial defined daily dose in neonatal population.

BACKGROUND: Antimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates. METHODS: Neonates (<1 month-old) from 6 Spanish hospitals during a 12-months period were included. Weight and weeks gestational age of each neonate were the variables collected. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication selected by the Delphi method. RESULTS: A total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01). CONCLUSIONS: A useful method for antimicrobial DDD measurement in neonatology has been designed to monitor antimicrobial consumption in hospital settings. It should be validated in further studies and thereby included in the design for neonatal antimicrobial stewardship programs in the future.

[Adecuacy of pediatric antimicrobial prescribing in the Emergency Department at discharge]. / Adecuación de la prescripción de antimicrobianos en procesos ambulatorios atendidos en Urgencias.

INTRODUCTION: In January 2019, Community of Madrid's Health Department published a guide about the use of antimicrobials in outpatient children. Taking this regional Guide as reference, this study was aimed at estimating the adequacy of the antimicrobial stewardship at discharge from a pediatric Emergency Department (ED). Secondarily, the differences in adequacy according to the diagnosis and the prescriber were studied, and the agreement between this Guide and the protocols of the ED was assessed. MATERIAL AND METHODS: An observational, descriptive, retrospective study was conducted on patients under 16 years old, with a diagnosis included in the regional Guide who were discharged from a pediatric ED between March of 2018 and February of 2019. Prescription was considered adequate when the indication, the antibiotic and the posology (dosage, dosing interval, length of treatment and route of administration) were correct. RESULTS: 165 out of 648 (25,5%) infectious diseases processes analyzed received antimicrobial treatment. In 23 processes treated with antimicrobial, the adequacy could not be evaluated due to the absence of data necessary to assess any aspect of posology. Therapy was considered appropriate in 550/625 processes (88.0%). When antimicrobial treatment was prescribed, 70/142 (49.3%) were appropriate and no statistically significant differences in adequacy were found between prescribers. Posology was the worst handled point of the prescription (26.3%). Tract urinary infection, conjunctivitis and otitis media were the pathologies with the lowest adecuacy (44.4%; 50.0% and 52.2%) and presented the highest discrepancy between the Guide and the center protocols (k=0.308; k=0.000; k=0.586). CONCLUSIONS: The adequacy of the management of infectious processes to the reference Guide in our pediatric ED was high, but it was below 50% when antimicrobial treatment was required. The degree of adequacy to the local protocols of the center was greater than to the regional Guide. This reveals a discrepancy between the 2documents that should be analyzed and corrected according to the available scientific evidence.

COVID-19 in hospitalised patients in Spain: a cohort study in Madrid.

Few large series describe the clinical characteristics, outcomes and costs of COVID-19 in Western countries. This cohort reports the first 1255 adult cases receiving anti-COVID-19 treatment at a Spanish hospital (1-24 March 2020). Treatment costs were calculated. A logistic regression model was used to explore risk factors on admission associated with ARDS. A bivariate Cox proportional hazard ratio (HR) model was employed to determine the HR between individual factors and death. We included 1255 patients (median age 65 years; 57.8% male), of which 92.3% required hospitalisation. The prevalence of hypertension, cardiovascular disease and diabetes mellitus (DM) was 45.1%, 31.4% and 19.9%, respectively. Lymphocytopenia (54.8%), elevated alanine aminotransferase (33.0%) and elevated lactate dehydrogenase (58.5%) were frequent. Overall, 36.7% of patients developed ARDS, 10.0% were admitted to an ICU and 21.3% died. The most frequent antiviral combinations were lopinavir/ritonavir plus hydroxychloroquine (44.2%), followed by triple therapy with interferon beta-1b (32.7%). Corticosteroids and tocilizumab were used in 25.3% and 12.9% of patients, respectively. Total cost of anti-COVID-19 agents was €511 825 (€408/patient). By multivariate analysis, risk factors associated with ARDS included older age, obesity, DM, severe hypoxaemia, lymphocytopenia, increased creatine kinase and increased C-reactive protein. In multivariate Cox model, older age (HR 1.07, 95% CI 1.06-1.09), cardiovascular disease (HR 1.34, 95% CI 1.01-1.79), DM (HR 1.45, 95% CI 1.09-1.92), severe hypoxaemia (HR 2.01, 95% CI 1.49-2.72), lymphocytopenia (HR 1.62, 95% CI 1.20-2.20) and increased C-reactive protein (HR 1.04, 95% CI 1.02-1.06) were risk factors for mortality.

Antimicrobial defined daily dose in neonatal population.

BACKGROUND: Antimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates. METHODS: Neonates (<1 month-old) from 6 Spanish hospitals during a 12-months period were included. Weight and weeks gestational age of each neonate were the variables collected. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication selected by the Delphi method. RESULTS: A total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01). CONCLUSIONS: A useful method for antimicrobial DDD measurement in neonatology has been designed to monitor antimicrobial consumption in hospital settings. It should be validated in further studies and thereby included in the design for neonatal antimicrobial stewardship programs in the future.

Clinical course of severe patients with COVID-19 treated with tocilizumab: report from a cohort study in Spain.

Background: We report the long-term outcomes, changes in laboratory parameters, the incidence of secondary nosocomial infections and treatment cost of a Spanish cohort of patients with severe COVID-19 that received tocilizumab (TCZ).Methods: Retrospective cohort of PCR confirmed adult patients who received TCZ from March 1 to 24, 2020 in a tertiary hospital was analyzed. Patients were followed up until 10 May 2020.Results: We included 162 patients (median age 64 years; 70.4% male). At time of TCZ administration, 48.1% of patients were on invasive mechanical ventilation (IMV). Over a median follow-up of 53 days, 46.9% of patients were discharge in good conditions and 19.8% were still hospitalized. The overall mortality was 33.3%, being higher in patients on IMV than those who did not (46.2% vs 26.7%, P < 0.001). A significant improvement in the lymphocyte count, C-reactive protein, lactate dehydrogenase, and D-dimer was observed. Overall, 43.2% patients presented nosocomial infections, causing death in 8%. Infections were more prevalent in ICU units (63.0% vs 17.1%, P < 0.001). The total cost of TCZ was €371,784.Conclusions: Among the patients who used TCZ, one third died, regardless the improvement in some inflammatory biomarkers. The incidence of secondary nosocomial infections was high.

Standardization and Chemical Characterization of Intravenous Therapy in Adult Patients: A Step Further in Medication Safety.

BACKGROUND: Intravenous drug administration is associated with potential complications, such as phlebitis. The physiochemical characteristics of the infusate play a very important role in some of these problems. AIM: The aim of this study was to standardize the dilutions of intravenous drugs most commonly used in hospitalized adult patients and to characterize their pH, osmolarity and cytotoxic nature to better guide the selection of the most appropriate vascular access. METHODS: The project was conducted in three phases: (i) standardization of intravenous therapy, which was conducted using a modified double-round Delphi method; (ii) characterization of the dilutions agreed on in the previous phase by means of determining the osmolarity and pH of each of the agreed concentrations, and recording the vesicant nature based on the information in literature; and (iii) algorithm proposal for selecting the most appropriate vascular access, taking into account the information gathered in the previous phases. RESULTS: In total, 112 drugs were standardized and 307 different admixtures were assessed for pH, osmolarity and vesicant nature. Of these, 123 admixtures (40%), had osmolarity values >600 mOsm/L, pH < 4 or > 9, or were classified as vesicants. In these cases, selection of the most suitable route of infusion and vascular access device is crucial to minimize the risk of phlebitis-type complications. CONCLUSIONS: Increasing safety of intravenous therapy should be a priority in the healthcare settings. Knowing the characteristics of drugs to assess the risk involved in their administration related to their physicochemical nature may be useful to guide decision making regarding the most appropriate vascular access and devices.

Pharmacotherapeutic review and update of idiopathic nephrotic syndrome in children.

AIM OF THE REVIEW: The therapeutic management of pediatric idiopathic nephrotic syndrome is still a challenge due to the large number of potentially effective pharmacological alternatives and the insufficient scientific evidence available. A bibliographic review was performed in order to identify the available pharmacological alternatives, as well as their place in therapy, and to analyze whether the treatment algorithm developed by the pediatric nephrology department of our hospital is consistent with the evidence published to date. METHOD: A literature search was carried out on MEDLINE, through PubMed, using the medical subject heading (MeSH) nephrotic syndrome. The search was limited to review papers, meta-analyses, clinical practice guidelines, and randomized controlled trials performed on pediatric populations up to September 2009. RESULTS: The treatment algorithm established in our hospital is consistent with the evidence available. Prednisone constitutes the first line treatment with evidence level Ia. When corticosteroids do not achieve remission, there are other therapeutic options that are not clearly positioned yet and further studies that provide more information on their comparative efficacy and safety are needed. These alternative therapeutic options are cyclosporine, mycophenolate mofetil, levamisol, cyclophosphamide and methylprednisolone, as independent strategies or as part of "Mendoza Protocol", tacrolimus and rituximab. Their sequence of introduction in the therapeutic scheme of NS is classified as evidence level IV and grade D recommendation. CONCLUSION: The wide range of options available for the pharmacotherapeutic management of NS and the lack of evidence about the comparative efficacy and safety of the different therapeutic strategies, make its positioning rather difficult. Therefore each hospital needs to draw up protocols based not only on the small amount of evidence available, but also on the authorized indications, availability of the drugs, clinical experience, associated costs, and patient preferences with regard to the duration of treatment, incidence and type of adverse effects. Development of new randomized controlled trials should be encouraged and setting up national plans for the treatment of this pathology might be a good approach for this problem.