A Case of Enterococcal Patent Ductus Arteriosus-associated Endarteritis in a Preterm Neonate.

INTRODUCTION: The persistent patency of the ductus arteriosus frequently occurs in premature neonates and can cause infective endocarditis (IE) or ductal endarteritis (DE) during sepsis. Even though neonatal IE and DE are believed to be a rare eventuality, their incidence has been increasing in the last decades due to the improved survival of even more preterm babies, favored by highly invasive procedures and therapies. In parallel, antimicrobial resistance is another rising problem in neonatal intensive care units, which frequently compels to treat infections with broad-spectrum or last generation antibiotics. CASE PRESENTATION: We report the case of a preterm neonate affected by patent ductus arteriosus-associated DE that followed an episode of sepsis caused by a high-level aminoglycoside-resistant enterococcus. The neonate was successfully treated with the synergistic combination of ampicillin and cefotaxime. DISCUSSION: IE and patent ductus arteriosus-associated DE are rising inside neonatal intensive care units and neonatologists should be aware of these conditions. Enterococcal IE and patent ductus arteriosus-associated DE sustained by high-level aminoglycoside-resistant strains can be successfully treated with the synergistic combination of ampicillin and cefotaxime even in preterm neonates.

External Validation of a Multivariate Model for Targeted Surfactant Replacement.

INTRODUCTION: Early targeted surfactant therapy for preterm infants is recommended but the best criteria to personalize treatment are unclear. We validate a previously published multivariate prognostic model based on gestational age (GA), lung ultrasound score (LUS), and oxygen saturation to inspire oxygen fraction ratio (SatO2/FiO2) using an independent data set. METHODS: Pragmatic, observational study in 10 Italian and Spanish NICUs, including preterm babies (250 and 336 weeks divided into 3 GA intervals) with clinical signs of respiratory distress syndrome and stabilized on CPAP. LUS and SatO2/FiO2 were collected soon after stabilization. Their prognostic accuracy was evaluated on the subsequent surfactant administration by a rigorously masked physician. RESULTS: One hundred seventy-five infants were included in the study. Surfactant was given to 74% infants born at 25-27 weeks, 38.5% at 28-30 weeks, and 26.5% at 31-33 weeks. The calibration curve comparing the validation and the development populations showed significant overlap with an intercept = 0.08, 95% CI (-0.34; 0.5) and a slope = 1.53, 95% CI (1.07-1.98). The validation cohort had a high predictive accuracy. Its ROC curve showed an AUC = 0.95, 95% CI (0.91-0.99) with sensitivity = 0.93, 95% CI (0.83-0.98), specificity = 0.81, 95% CI (0.73-0.88), PPV = 0.76, 95% CI (0.65-0.84), NPV = 0.95, 95% CI (0.88-0.98). LUS ≥9 demonstrated the highest sensitivity (0.91, 95% CI [0.82-0.97]) and specificity = 0.81, 95% CI (0.72-0.88) as individual predictor. LUS and SatO2/FiO2 prognostic performances varied with GA. CONCLUSION: We validated a prognostic model based on LUS and Sat/FiO2 to facilitate early, customized surfactant administration that may improve respiratory management of preterm neonates.

Ultrasound-assessed lung aeration correlates with respiratory system compliance in adults and neonates with acute hypoxemic restrictive respiratory failure: an observational prospective study.

BACKGROUND: Lung ultrasound allows lung aeration to be assessed through dedicated lung ultrasound scores (LUS). Despite LUS have been validated using several techniques, scanty data exist about the relationships between LUS and compliance of the respiratory system (Crs) in restrictive respiratory failure. Aim of this study was to investigate the relationship between LUS and Crs in neonates and adults affected by acute hypoxemic restrictive respiratory failure, as well as the effect of patients' age on this relationship. METHODS: Observational, cross-sectional, international, patho-physiology, bi-center study recruiting invasively ventilated, adults and neonates with acute respiratory distress syndrome (ARDS), neonatal ARDS (NARDS) or respiratory distress syndrome (RDS) due to primary surfactant deficiency. Subjects without lung disease (NLD) and ventilated for extra-pulmonary conditions were recruited as controls. LUS, Crs and resistances (Rrs) of the respiratory system were measured within 1 h from each other. RESULTS: Forty adults and fifty-six neonates were recruited. LUS was higher in ARDS, NARDS and RDS and lower in control subjects (overall p < 0.001), while Crs was lower in ARDS, NARDS and RDS and higher in control subjects (overall p < 0.001), without differences between adults and neonates. LUS and Crs were correlated in adults [r = - 0.86 (95% CI - 0.93; - 0.76), p < 0.001] and neonates [r = - 0.76 (95% CI - 0.85; - 0.62), p < 0.001]. Correlations remained significant among subgroups with different causes of respiratory failure; LUS and Rrs were not correlated. Multivariate analyses confirmed the association between LUS and Crs both in adults [B = - 2.8 (95% CI - 4.9; - 0.6), p = 0.012] and neonates [B = - 0.045 (95% CI - 0.07; - 0.02), p = 0.001]. CONCLUSIONS: Lung aeration and compliance of the respiratory system are significantly and inversely correlated irrespective of patients' age. A restrictive respiratory failure has the same ultrasound appearance and mechanical characteristics in adults and neonates.

In-hospital Outcomes and Early Hemodynamic Management According to Echocardiography Use in Hypotensive Preterm Infants: A National Propensity-Matched Cohort Study.

Background: Hypotension is a common condition during the first postnatal days of very preterm infants and has been associated with an increased risk of adverse outcomes but its management remains controversial. There is a consensus to promote the use of neonatologist-performed echocardiography (NPE) in hypotensive very preterm infants, although no clinical trial ever assessed this practice. Methods: We conducted a retrospective analysis of prospectively collected data from the French national EPIPAGE-2 cohort to evaluate the association of NPE with survival, severe morbidity, and therapeutic management in very preterm infants with early hypotension. Reasons for administering antihypotensive treatments were also analyzed. We included infants born before 30 weeks of gestation with hypotension within 72 h of birth. Infants managed with (NPE group) or without (no-NPE group) NPE use were compared after matching on gestational age and a propensity score, reflecting each patient's probability of having an NPE based on his/her baseline covariates. This matching procedure intended to control for the indication bias of NPE. Results: Among 966 eligible infants, 809 were included (NPE group, n = 320; no-NPE group, n = 489), and 229 from each group could be matched. The NPE group did not differ significantly from the no-NPE group for survival (OR 1.01, 95% CI 0.64 to 1.60; p = 0.95) or survival without severe morbidity at discharge (OR 0.92, 95% CI 0.63 to 1.34; p = 0.66), but received more antihypotensive treatments [144/229 (62.9%) vs. 99/229 (43.0%), p < 0.001]. Isolated hypotension was the main reason for treatment in both groups. Among treated infants, volume expansion was administered at equal rates to the NPE and no-NPE groups [118/144 (82.1%) vs. 79/99 (80.1%), p = 0.67], but the NPE group received inotropic drugs more often [77/144 (53.7%) vs. 37/99 (37.8%), p = 0.023]. Conclusion: NPE use in hypotensive preterm infants was not associated with in-hospital outcomes and had little influence on the nature of and reasons for antihypotensive treatments. These results suggest the need to optimize NPE use.

Secretory phospholipase A2 expression and activity in preterm clinical chorioamnionitis with fetal involvement.

Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.e., the presence of intrauterine inflammation) is also often associated with preterm birth. We aimed to verify if chorioamnionitis with fetal involvement modifies sPLA2 activity and expression profile in mothers and neonates delivered prematurely. We collected maternal plasma and amniotic fluid, as well as bronchoalveolar lavage fluid from preterm neonates born to mothers with or without clinical chorioamnionitis with fetal involvement. We measured concentrations of sPLA2 subtype-IIA and -IB, total enzyme activity, and proteins. Urea ratio was used to obtain epithelial lining fluid concentrations. Enzyme activity measured in maternal plasma (P < 0.001) and amniotic fluid (P < 0.001) was higher in chorioamnionitis cases than in controls. This was mainly due to the increased production of sPLA2-IIA, as the subtype -IB was present in a smaller amount and was similar between the two groups; sPLA2-IIA was increased in epithelial lining fluid (P = 0.045) or increased, although without statistical significance, in maternal plasma (P = 0.06) and amniotic fluid (P = 0.08) of chorioamnionitis cases. Cytokines that are known to increase sPLA2-IIA expression (TNF-α and IL-1ß) or whose expression was increased by sPLA2-IIA (IL-8) were higher in histologically confirmed chorioamnionitis [TNF-α (P = 0.028), IL-1ß (P < 0.001), and IL-8 (P = 0.038)]. These data represent the basis for future studies on sPLA2-IIA inhibition to prevent deleterious consequences of chorioamnionitis and preterm birth.

Cor Triatriatum Dexter: Contrast Echocardiography Is Key to the Diagnosis of a Rare but Treatable Cause of Neonatal Persistent Cyanosis.

Cor triatriatum dexter (CTD) is an extremely uncommon and underreported congenital cardiac anomaly in which the persistence of the embryonic right venous valve separates the right atrium into two chambers with varying degrees of obstruction to antegrade flow and variable degree of right to left shunt at atrial level. Depending on the size of the valves, clinical manifestations vary from absence of symptoms to severe hypoxia, requiring urgent surgical correction. We herein describe the diagnostic difficulties in a case of neonatal CTD, who developed increasingly severe and unresponsive cyanosis, first interpreted as postnatal maladjustment with pulmonary hypertension. The failure to respond to oxygen and pulmonary vasodilators led us to reconsider a different diagnosis. The use of contrast echocardiography improved the diagnostic performance of transthoracic echocardiogram (TTE) and revealed a massive right-to-left shunt secondary to the presence of an atrial membrane that required urgent surgery.

Synthesis and systematic review of reported neonatal SARS-CoV-2 infections.

A number of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections have been reported in neonates. Here, we aim to clarify the transmission route, clinical features and outcomes of these infections. We present a meta-analysis of 176 published cases of neonatal SARS-CoV-2 infections that were defined by at least one positive nasopharyngeal swab and/or the presence of specific IgM. We report that 70% and 30% of infections are due to environmental and vertical transmission, respectively. Our analysis shows that 55% of infected neonates developed COVID-19; the most common symptoms were fever (44%), gastrointestinal (36%), respiratory (52%) and neurological manifestations (18%), and lung imaging was abnormal in 64% of cases. A lack of mother-neonate separation from birth is associated with late SARS-CoV-2 infection (OR 4.94 (95% CI: 1.98-13.08), p = 0.0002; adjusted OR 6.6 (95% CI: 2.6-16), p < 0.0001), while breastfeeding is not (OR 0.35 (95% CI: 0.09-1.18), p = 0.10; adjusted OR 2.2 (95% CI: 0.7-6.5), p = 0.148). Our findings add to the literature on neonatal SARS-CoV-2 infections.

Surfactant-secreted phospholipase A2 interplay and respiratory outcome in preterm neonates.

Secreted phospholipase A2 hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: 1) identify phospholipases A2 isoforms expressed in preterm lung; 2) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and 3) verify whether phospholipase A2 is linked to respiratory outcomes. In bronchoalveolar lavages of preterm neonates, we measured enzyme activity (alone or with inhibitors), enzyme subtypes, surfactant protein-A, and inflammatory mediators. Surfactant function and phospholipid profile were also tested. Urea ratio was used to obtain epithelial lining fluid concentrations. Follow-up data were prospectively collected. Subtype-IIA is the main phospholipase isoform in preterm lung, although subtype-IB may be significantly expressed. Neonates needing surfactant retreatment have higher enzyme activity (P = 0.021) and inflammatory mediators (P always ≤ 0.001) and lower amounts of phospholipids (P always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = -0.6; P = 0.008; adjusted P = 0.009), total phospholipids (ρ = -0.475; P = 0.05), and phosphatidylcholine (ρ = -0.622; P = 0.017). Exogenous surfactant significantly reduced global phospholipase activity (P < 0.001) and subtype-IIA (P = 0.005) and increased dioleoylphosphatidylglycerol (P < 0.001) and surfactant adsorption (P < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, P = 0.005; adjusted P = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ-b = 0.349, P = 0.037; adjusted P = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.

Short- and long-term respiratory outcomes in neonates with ventilator-associated pneumonia.

BACKGROUND AND OBJECTIVE: Ventilator-associated pneumonia (VAP) is a common nosocomial infection in critical care settings and might have important long-term consequences in neonates. Our aim is to clarify the short- and long-term respiratory outcomes of neonates affected by VAP. METHODS: Prospective, population-based, cohort study with 12 months follow-up based on clinical examinations and diary-based respiratory morbidity score, conducted in an academic tertiary referral neonatal unit with dedicated follow-up program. RESULTS: A total of 199 inborn neonates consecutively ventilated for at least 48 hours were eligible for the study. One hundred fifty-one were finally enrolled and classified as "exposed" or "unexposed" to VAP, if they fulfilled (or not) VAP criteria once during their stay. Bronchopulmonary dysplasia (BPD) incidence was significantly higher in exposed (75%) than in unexposed babies (26.8%; relative risk [RR]: 2.8 [1.9-4.0]; Adj RR: 3.5 [1.002-12.7]; P = .049; number needed to harm = 2.07), although the composite BPD/mortality did not differ. Exposed patients showed longer intensive care unit stay (87 [43-116] vs 14 [8-52] days; St.ß = 0.24; P < .0001) and duration of ventilation (15 [10-25] vs 5 [4-8] days; St.ß = 0.29; P < .0001) than unexposed neonates. Exposed patients also showed less ventilator-free days (11 [5-17.7] vs 22 [14-24] days; St.ß = -0.15; P = .05) compared to unexposed. Respiratory infections, use of drugs, rehospitalization for respiratory reasons, home oxygen therapy, their composite outcome, and diary-based clinical respiratory morbidity score were similar between the cohorts. CONCLUSION: Neonatal VAP seems associated to higher incidence of BPD, longer ventilation, and intensive care stay but it does not affect long-term respiratory morbidity.

Echography-Guided Surfactant Therapy to Improve Timeliness of Surfactant Replacement: A Quality Improvement Project.

OBJECTIVE: To improve time of surfactant administration with a surfactant replacement protocol based on semiquantitative lung ultrasound score (LUS) thresholds. STUDY DESIGN: Quality improvement (QI), prospective, before-after, pilot study. In a 6-month period surfactant replacement was based only on inspired oxygen fraction (FiO2) thresholds. In the second 6-month period, surfactant was given when either the FiO2 or LUS exceeded the limits. The main QI measures were the proportion of neonates receiving surfactant within the first 3 hours of life and maximal FiO2 reached before surfactant replacement. Secondary QI measures were the duration of respiratory support and ventilator-free days. Data were also collected for 1 year after the study to verify sustainability. RESULTS: Echography-guided Surfactant THERapy (ESTHER) increased the proportion of neonates receiving surfactant within the first 3 hours of life (71.4%-90%; P < .0001) and reduced the maximal FiO2 reached before surfactant replacement (0.33 [0.26-0.5]) vs 0.4 [0.4-0.55]; P = .005). The global need for surfactant did not significantly change. ESTHER also resulted in a significant decrease in duration of invasive ventilation and ventilator-free days. CONCLUSIONS: ESTHER improved the timeliness of surfactant administration and secondary QI indicators related to surfactant replacement.

Estimation of early life endogenous surfactant pool and CPAP failure in preterm neonates with RDS.

BACKGROUND: It is not known if the endogenous surfactant pool available early in life is associated with the RDS clinical course in preterm neonates treated with CPAP. We aim to clarify the clinical factors affecting surfactant pool in preterm neonates and study its association with CPAP failure. METHODS: Prospective, pragmatic, blind, cohort study. Gastric aspirates were obtained (within the first 6 h of life and before the first feeding) from 125 preterm neonates with RDS. Surfactant pool was measured by postnatal automated lamellar body count based on impedancemetry, without any pre-analytical treatment. A formal respiratory care protocol based on European guidelines was applied. Clinical data and perinatal risk factors influencing RDS severity or lamellar body count were real-time recorded. Investigators performing lamellar body count were blind to the clinical data and LBC was not used in clinical practice. RESULTS: Multivariate analysis showed gestational age to be the only factor significantly associated with lamellar body count (standardized ß:0.233;p = 0.023). Lamellar body count was significantly higher in neonates with CPAP success (43.500 [23.750-93.750]bodies/µL), than in those failing CPAP (20.500 [12.250-49.750] bodies/µL;p = 0.0003).LBC had a moderate reliability to detect CPAP failure (AUC: 0.703 (0.615-0.781);p < 0.0001; best cut-off: ≤30,000 bodies/µL). Upon adjustment for possible confounders, neither lamellar body count, nor its interaction factor with gestational age resulted associated with CPAP failure. CONCLUSIONS: Early postnatal lamellar body count on gastric aspirates in CPAP-treated preterm neonates with RDS is significantly influenced only by gestational age. Lamellar bodies are not associated with CPAP failure. Thus, the endogenous surfactant pool available early in life only has a moderate reliability to predict CPAP failure.

A collaborative intervention to improve surgical antibiotic prophylaxis in children: results from a prospective multicenter study.

PURPOSE: The use of surgical antibiotic prophylaxis (SAP) in children is poorly characterized. Our aim was to evaluate the effectiveness of a quality improvement (QI) intervention targeting SAP in children, by means of a multicenter prospective intervention study, with a before and after design. METHODS: We prospectively investigated elective surgical procedures performed in children <18 years, prior to the QI intervention, after the intervention and at 9-month follow-up. The primary outcomes were adherence to SAP indications and SAP appropriateness, defined considering antibiotic choice, timing of first dose and duration of administration. We compared SAP adherence and appropriateness prior the QI intervention, to the post-intervention and the follow-up. We considered patient and procedure characteristics as covariates in two logistic regression models to assess the effect of the QI intervention on SAP adherence and appropriateness. RESULTS: We collected information on 2383 procedures (pre-intervention: 784; post-intervention: 790; follow-up: 809). The QI intervention had a significant impact on the adherence to SAP indications (86.6% in the post-intervention, compared to 82.0% prior to the intervention; p < 0.05), and on its appropriateness (35.7% compared to 19.9%; p < 0.01). The impact of the intervention on SAP appropriateness was maintained at follow-up (38.3%; p < 0.01 compared to pre-intervention). All components of SAP appropriateness significantly improved after the intervention and at follow-up. The logistic regression analyses confirmed the effect of intervention in improving adherence to SAP indications and appropriateness. CONCLUSIONS: Following the QI intervention, there was a significant improvement in quality of SAP in pediatric surgery, though more efforts are needed to increase SAP appropriateness.

Surgical antibiotic prophylaxis in children: a mixed method study on healthcare professionals attitudes.

BACKGROUND: Qualitative and quantitative research investigating determinants of adherence to clinical guidelines (GLs) on surgical antibiotic prophylaxis (SAP) are scarce. We conducted a mixed-method study aimed at investigating barriers and at describing attitudes of healthcare professionals (HCPs) regarding SAP in three Italian children's hospitals. METHODS: The study comprised two sequential phases: 1) collection of qualitative data through focus groups; 2) conduction of a survey on HCPs attitudes towards SAP. Focus groups were carried out in each hospital with a theoretical convenience sample of 10-15 HCPs. Categorical analysis was conducted. Emerging categories and additional topics derived by literature search were used to develop the survey questionnaire, which included 13 questions expressed through a 4-point Likert scale. Members of surgical teams were invited by e-mail to fill in the questionnaire. We summed up the points assigned to each 4-point Likert scale response and calculated a cumulative score expressing overall concordance to expected HCPs attitudes on SAP. We conducted univariate and multivariate analysis to evaluate the relationship among characteristics of respondents and concordance with expected attitudes. RESULTS: The main categories identified in the qualitative phase included determinants of general adherence to GLs (e.g., relevance of clinical judgment), individual determinants (e.g., poor knowledge on hospital data) and organizational/structural determinants (e.g., patient flows). A total of 357 HCPs participated in the survey (response rate: 82.1%). Among respondents, 75% reported that SAP should be performed with first or second-generation cephalosporins, 44% that 2-3 days of antibiotic administration are useful as a precaution after surgery, 32% that SAP is needed for all surgical procedures. At multivariate analysis, professional category (physicians vs nurses; OR: 3.31; 95%CI: 1.88-5.82), and hospital (hospital 1 and 2 vs hospital 3; ORs: 2.79, 95%CI: 1.22-6.36; 2.40, 95%CI: 1.30-4.43, respectively) were significantly and independently associated with higher concordance with expected attitudes on SAP. CONCLUSIONS: Results from this study were useful to identify obstacles to appropriate SAP use in children. In our setting, findings support that a quality-improvement intervention should take into account local contexts, with development of hospital policies, education on SAP recommendations, and dissemination of data on adherence to recommendations.

A Multicentric Prospective Incidence Study of Guillain-Barré Syndrome in Italy. The ITANG Study.

BACKGROUND: To assess Guillain-Barré syndrome (GBS) incidence we relied on the Italian Network for the study of GBS (ITANG) established in 2010 in 7 Italian regions to analyse the association between influenza vaccination and GBS. METHODS: All individuals aged ≥18 years, presenting with clinical manifestations that suggested GBS according to the universally accepted Asbury's diagnostic criteria (1990) were prospectively notified to a centralised database by ITANG neurologists over the period October 1, 2010-September 30, 2011. Through a telephone survey, 9 trained interviewers followed up the cases to diagnosis and then for 1 year since hospital discharge. Validation of case reporting was performed with the support of administrative data in 5 regions. RESULTS: We found 365 cases fulfilling the definition for GBS or one of its variants over 19,846,068 population ≥18 years of age, yielding an annual incidence rate of 1.84 per 100,000 (95% CI 1.65-2.03), 2.30 (95% CI 1.99-2.60) in men and 1.41 (95% CI 1.18-1.64) in women. A highly significant peak of incidence was observed in February 2011 as compared to reference month (September 2011, rate ratio 3.3:1, p < 0.01). CONCLUSIONS: In Italy, GBS incidence was among the highest reported in Europe and higher than previously observed in Italian studies.

Post-operative benefits of animal-assisted therapy in pediatric surgery: a randomised study.

BACKGROUND: Interest in animal-assisted therapy has been fuelled by studies supporting the many health benefits. The purpose of this study was to better understand the impact of an animal-assisted therapy program on children response to stress and pain in the immediate post-surgical period. PATIENTS AND METHODS: Forty children (3-17 years) were enrolled in the randomised open-label, controlled, pilot study. Patients were randomly assigned to the animal-assisted therapy-group (n = 20, who underwent a 20 min session with an animal-assisted therapy dog, after surgery) or the standard-group (n = 20, standard postoperative care). The study variables were determined in each patient, independently of the assigned group, by a researcher unblinded to the patient's group. The outcomes of the study were to define the neurological, cardiovascular and endocrinological impact of animal-assisted therapy in response to stress and pain. Electroencephalogram activity, heart rate, blood pressure, oxygen saturation, cerebral prefrontal oxygenation, salivary cortisol levels and the faces pain scale were considered as outcome measures. RESULTS: After entrance of the dog faster electroencephalogram diffuse beta-activity (> 14 Hz) was reported in all children of the animal-assisted therapy group; in the standard-group no beta-activity was recorded (100% vs 0%, p<0.001). During observation, some differences in the time profile between groups were observed for heart rate (test for interaction p = 0.018), oxygen saturation (test for interaction p = 0.06) and cerebral oxygenation (test for interaction p = 0.09). Systolic and diastolic blood pressure were influenced by animal-assisted therapy, though a higher variability in diastolic pressure was observed. Salivary cortisol levels did not show different behaviours over time between groups (p=0.70). Lower pain perception was noted in the animal-assisted group in comparison with the standard-group (p = 0.01). CONCLUSION: Animal-assisted therapy facilitated rapid recovery in vigilance and activity after anaesthesia, modified pain perception and induced emotional prefrontal responses. An adaptative cardiovascular response was also present. TRIAL REGISTRATION: ClinicalTrials.gov NCT02284100.

Surgical antibiotic prophylaxis in children: adherence to indication, choice of agent, timing, and duration.

PURPOSE: Surgical antibiotic prophylaxis (SAP) in children is poorly characterized. We investigated SAP for children undergoing elective surgical procedures. METHODS: We prospectively investigated elective surgical procedures performed in children <18 years, from November 2012 to February 2013, in three tertiary-care children's hospitals in Italy. Data were derived from clinical records. Antibiotics were considered prophylactic if given by parenteral route during the same day of the procedure. SAP indication was defined according to international guidelines. Whenever SAP was indicated, it was defined appropriate if antibiotic choice was different from third-/fourth-generation cephalosporins, carbapenems, or piperacillin/tazobactam; timing of first dose was within 60 min before incision; and duration of administration was ≤24 h. Multivariable logistic regression model was used to assess independent predictors of adherence to SAP administration, for procedures with SAP indication performed in all hospitals. RESULTS: Data on 765 procedures were collected. SAP was administered in 81% of 206 procedures with SAP indication and in 18% of 559 procedures with no indication. Type of procedure and hospital were significantly associated with adherence of administration to SAP indication. In the 206 procedures where SAP was indicated, overall appropriateness of antibiotic choice, timing, and duration was 8%. CONCLUSIONS: The SAP rate observed in procedures with SAP indication and the appropriateness of drug choice, timing, and duration are reasons of concern. Quality improvement interventions for implementing SAP recommendations in children are strongly needed, and their impact should be evaluated at hospital level.

The impact of regional co-payment and national reimbursement criteria on statins use in Italy: an interrupted time-series analysis.

BACKGROUND: Statins are among the most commonly prescribed drugs worldwide in the prevention of cardiovascular diseases and their effectiveness is largely acknowledged. The consumption of statins increased four-fold during the 2000-2010 decade in Italy and national and regional control policies were developed. Restrictions to reimbursement were fixed at the national level, whereas co-payment was introduced in some, but not all, regions. The aim of the present study is to assess the impact of such policies on the consumption of statins in Italy between 2001-2007 among outpatients. METHODS: The statin use was measured in terms of defined daily doses per 1,000 inhabitants per day (DDD/1000 inh. day) from May 2001 to December 2007. The study was conducted in 17 out of 21 regions, nine of which had implemented a co-payment policy. Time trends in consumption before and after the introduction of co-payment policies and reimbursement criteria were examined using segmented regression analysis of interrupted time-series, adjusting for seasonal components. RESULTS: The consumption of statins increased by 22.9 DDD/1000 inh. day in May 2001 to 54.7 DDD/1000 inh. day in December 2007. On average, there was a 1.7% increase in statin use each month before the national guideline changed while the increase was about 0.5% afterwards. The revision of the reimbursement criteria was associated with a significant decrease in level (coefficient = -2.80, 95% CI -3.70 to -1.90 p-value <0.001) and trend (coefficient = -0.33, 95% CI -0.37 to -0.29 p-value <0.001). The introduction of co-payment was associated with a significant change in trend of consumption so that the overall use of the drug increased by 0.04 (95% CI 0.02 to 0.07, p-value < 0.001) DDD/1000 inh. day per month in the post-intervention period, but there was no evidence of a change in level of consumption (p-value = 0.163). CONCLUSIONS: Consumption of statins in Italy increased almost three-fold during the study period. The restriction to reimbursement Interventions was associated with an immediate drop and a decrease in trend of statin use, while the regional copayment was associated with a small increase in trend of statin use.