Acute kidney injury in children hospitalised for febrile urinary tract infection.

AIM: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. METHODS: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. RESULTS: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8-15.2; p = 9.4e-09) and neutrophils levels (OR = 1.13; 95%CI: 1.08-1.2; p = 6.8e-07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7-6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. CONCLUSION: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.

Acute pharyngitis in children and adults: descriptive comparison of current recommendations from national and international guidelines and future perspectives.

This study aims to provide a comparison of the current recommendations about the management of acute pharyngitis. A literature search was conducted from January 2009 to 2023. Documents reporting recommendations on the management of acute pharyngitis were included, pertinent data were extracted, and a descriptive comparison of the different recommendations was performed. The quality of guidelines was assessed through the AGREE II instrument. Nineteen guidelines were included, and an overall moderate quality was found. Three groups can be distinguished: one group supports the antibiotic treatment of group A ß-hemolytic Streptococcus (GABHS) to prevent acute rheumatic fever (ARF); the second considers acute pharyngitis a self-resolving disease, recommending antibiotics only in selected cases; the third group recognizes a different strategy according to the ARF risk in each patient. An antibiotic course of 10 days is recommended if the prevention of ARF is the primary goal; conversely, some guidelines suggest a course of 5-7 days, assuming the symptomatic cure is the goal of treatment. Penicillin V and amoxicillin are the first-line options. In the case of penicillin allergy, first-generation cephalosporins are a suitable choice. In the case of beta-lactam allergy, clindamycin or macrolides could be considered according to local resistance rates.    Conclusion: Several divergencies in the management of acute pharyngitis were raised among guidelines (GLs) from different countries, both in the diagnostic and therapeutic approach, allowing the distinction of 3 different strategies. Since GABHS pharyngitis could affect the global burden of GABHS disease, it is advisable to define a shared strategy worldwide. It could be interesting to investigate the following issues further: cost-effectiveness analysis of diagnostic strategies in different healthcare systems; local genomic epidemiology of GABHS infection and its complications; the impact of antibiotic treatment of GABHS pharyngitis on its complications and invasive GABHS infections; the role of GABHS vaccines as a prophylactic measure. The related results could aid the development of future recommendations. What is Known: • GABHS disease spectrum ranges from superficial to invasive infections and toxin-mediated diseases. • GABHS accounts for about 25% of sore throat in children and its management is a matter of debate. What is New: • Three strategies can be distinguished among current GLs: antibiotic therapy to prevent ARF, antibiotics only in complicated cases, and a tailored strategy according to the individual ARF risk. • The impact of antibiotic treatment of GABHS pharyngitis on its sequelae still is the main point of divergence; further studies are needed to achieve a global shared strategy.

Nano-antenna array for high efficiency sunlight harvesting.

Solar rectennas are promising devices for energy harvesting. Capability of rectennas to convert incident light into useful energy depends on the antenna efficiency, that is the ratio between the power transferred to the load vs the incoming power. In this work, we first emphasize that for the efficiency to be calculated accurately, antennas need to be treated as receiving devices, not as transmitting ones. Then, we propose an arrangement of antennas that differs from those published so far in three respects: (1) the proposed arrangement is formed by an array of nano-antennas with sub-wavelength inter-element spacing, (2) it comprises a reflecting mirror, and (3) it allows for dual polarization operation. Through numerical simulations, we show that the small lattice pitch we use is responsible for frequency flattening of the lattice impedance over the whole solar spectrum, eventually allowing for excellent matching with the antennas' loads. Also, the small pitch allows for a smooth dependence of the receiving efficiency on the angle of incidence of sunlight. Finally, we show numerically that the reflecting mirror also allows for an almost complete cancellation of light scattered by the receiving antennas. The final result is a polarization insensitive receiving theoretical efficiency larger than 70% over the whole 300-3000 nm spectral range, with a less than 10% energy wasting due to back-scattering of sunlight.

Midazolam premedication in ileocolic intussusception: a retrospective multicenter study.

Ileocolic intussusception is a common cause of bowel obstruction. When spontaneous reduction does not occur, non-operative management through enema reduction is necessary. Despite the evidence indicating that sedatives favor success in the reduction, their use is still not a common practice. To determine if midazolam (MDZ) before enema improves the rate of procedure success, we retrospectively reviewed charts of patients admitted to two Italian pediatric emergency departments. Outcome measures were the success rate of the enema, recurrence, and need for surgery. Patients were grouped according to the use of MDZ or not, before hydrostatic reduction attempt. We included 69 and 37 patients in the MDZ and non-MDZ groups, respectively. The two groups did not differ in demographics, clinical characteristics, and ultrasound findings. Intussusception reduction after the first enema attempt occurred in 75% (MDZ group) and 32.4% (non-MDZ group) of patients (P < .001); 27.9% (MDZ group) and 77.8% (non-MDZ group) of patients underwent surgery (P < .001). Among them, spontaneous reduction of intussusception during the induction of general anesthesia occurred in 31.6% and 42.9% of patients, respectively (P .43). Multivariate logistic regression analysis showed that only MDZ had a positive effect on the result of the enema (OR 7.602, 95%CI 2.669-21.652, P < .001). CONCLUSION: Procedural sedation with MDZ for enema reduction of intussusception can increase the success rate and lead to a better management of patients. WHAT IS KNOWN: • Despite the evidence of the usefulness of sedatives in the reduction of intussusception, their use is still not a common practice. WHAT IS NEW: • Midazolam during enema reduction of intussusception can increase the success rate and consequently lead to better management of patients.

Multicentre study revealed significant gaps between evidence-based recommendations for using corticosteroids for croup and clinical practice.

AIM: Adherence to croup management recommendations has been poorly investigated. This study aimed to describe the treatment patterns in two paediatric emergency departments and analyse the adherence to recommendations. METHODS: We conducted a retrospective chart review of children diagnosed with croup in two Italian paediatric emergency departments in 2017. Data on clinical presentation, corticosteroid administration and home therapy were collected. Length of stay, hospitalisation and re-access rates were compared among different corticosteroid treatment groups. RESULTS: We enrolled 632 patients (61.1% males) with a mean age of 42.8 ± 55.1 months. Corticosteroids were administered to 403 (63.8%) children in the emergency departments. Dexamethasone was administered to 1 (0.4%) patient. Inhaled and oral corticosteroids were given to 342 (54.1%) and 226 (35.8%) patients, respectively. Home therapy was prescribed for 603 (95.4%) patients, either with inhaled (86.2%) and/or oral (43.8%) corticosteroids. The re-access rate was 2.8%. The actual pharmaceutical costs were an estimated 10 times higher than they would have been if the recommendations had been followed. CONCLUSION: A significant gap between the evidence and clinical practice for croup treatment was observed. Improving adherence to the recommendations could lead to clinical and economic benefits.

Nanoscale Characterization of Graphene Oxide-Based Epoxy Nanocomposite Using Inverted Scanning Microwave Microscopy.

Scanning microwave microscopy (SMM) is a novel metrological tool that advances the quantitative, nanometric, high-frequency, electrical characterization of a broad range of materials of technological importance. In this work, we report an inverted near-field scanning microwave microscopy (iSMM) investigation of a graphene oxide-based epoxy nanocomposite material at a nanoscopic level. The high-resolution spatial mapping of local conductance provides a quantitative analysis of the sample's electrical properties. In particular, the electrical conductivity in the order of ∼10-1 S/m as well as the mapping of the dielectric constant with a value of ∼4.7 ± 0.2 are reported and validated by the full-wave electromagnetic modeling of the tip-sample interaction.

Heterodyne phase shifting method in scanning probe microscopy.

The present paper describes a novel implementation of the continuous phase shifting method (PSM), named heterodyne holography, in a scanning probe microscope configuration, able to retrieve the complex scattered field in on-axis configuration. This can be achieved by acquiring a continuous sequence of holograms at different wavelengths in just a single scan through the combination of scanning interference microscopy and a low-coherent signal acquired in the frequency domain. This method exploits the main advantages of the phase shifting technique and avoids some limits relative to off-axis holography in providing quantitative phase imaging.

Doctors' shortage in adults COVID-19 units: a call for pediatricians.

Since its first description in China, SARS-CoV-2 has been spreading all over the world causing millions of 31 infections and hundreds of thousands of deaths. The massive raise of cases all over the world even during the current second wave is leading to unprecedented pressures on healthcare services. Growing evidence is highlighting that COVID-19 is a systemic condition that requires doctors with multiple expertise. Paediatricians are trained in these skills. Considering the issue of staff shortage that is facing every country in the world, and the complexity of COVID-19, pediatricians may represent an important source of ready and skilled specialists that can quickly translate the pediatric practice in the COVID-19 care. In conclusion, we highlight through our experience several parallels between the pediatric clinical practice and clinical conditions described in patients with COVID-19 as well as the diagnostic tools and the measures taken in 39 patients with COVID-19. What is Known: • The massive raise of cases all over the world is leading to unprecedented pressures on healthcare services. • Growing evidence is highlighting that COVID-19 is a systemic condition that requires doctors with multiple expertise. What is New: • Pediatricians are trained daily in these skills. • Considering the issue of staff shortage that is facing every country in the world, and the complexity of COVID-19, pediatricians may represent an important source of ready and skilled specialists that can quickly translate the pediatric practice in the COVID-19 care.

Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab's usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.

Single-dose of ondansetron for vomiting in children and adolescents with acute gastroenteritis-an updated systematic review and meta-analysis.

This review aimed to meta-analyze evidence of efficacy and safety of one single dose of ondansetron for vomiting in children and adolescents with acute gastroenteritis. Database searches of MEDLINE (PubMed), Scopus (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up to November 2019 were performed. Only randomized clinical trials versus placebo were considered. Fixed and random effect models were used for the analyses of pooled data. Thirteen randomized clinical trials (2146 patients) were finally included. One single dose of ondansetron showed to produce (1) higher chance of vomiting cessation within 8 h (RR 1.41, 95% CI 1.19-1.68; low-quality evidence); (2) lower chances of oral rehydration therapy failure (RR 0.43, 95% CI 0.34-0.55; high-quality evidence), intravenous hydration needs (RR 0.44, 95% CI 0.34-0.57; high-quality evidence), and hospitalization rates within 8 h (RR 0.49, 95% CI 0.32-0.75; high-quality evidence); and (3) no statistically significant differences in return visits to emergency department (RR 1.14, 95% CI 0.74-1.76; high-quality evidence) compared with placebo. Further studies are necessary to better assess long term efficacy and safety of ondansetron in this context.Conclusions: Mixed evidence was found via few studies about the efficacy and safety of a single dose of ondansetron in the pediatric population.What is known:• Ondansetron use for vomiting in pediatric acute gastroenteritis is increasing worldwide.• Actual convictions come from studies evaluating one and more than one dose of the drug.What is new:• This is the first review to collect data about the effects of one single dose of ondansetron on strong and temporally homogeneous clinical outcomes.• This study supports the use of one dose of ondansetron in pediatric acute gastroenteritis.• Further studies are necessary to assess its long-term efficacy and safety.

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020.

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered.

Lung ultrasound for the diagnosis of pneumonia in children with acute bronchiolitis.

BACKGROUND: Guidelines currently do not recommend the routine use of chest x-ray (CXR) in bronchiolitis. However, CXR is still performed in a high percentage of cases, mainly to diagnose or rule out pneumonia. The inappropriate use of CXR results in children exposure to ionizing radiations and increased medical costs. Lung Ultrasound (LUS) has become an emerging diagnostic tool for diagnosing pneumonia in the last decades. The purpose of this study was to assess the diagnostic accuracy and reliability of LUS for the detection of pneumonia in hospitalized children with bronchiolitis and to evaluate the agreement between LUS and CXR in diagnosing pneumonia in these patients. METHODS: We enrolled children admitted to our hospital in 2016-2017 with a diagnosis of bronchiolitis and undergone CXR because of clinical suspicion of concomitant pneumonia. LUS was performed in each child by a pediatrician blinded to the patient's clinical, laboratory and CXR findings. An exploratory analysis was done in the first 30 patients to evaluate the inter-observer agreement between a pediatrician and a radiologist who independently performed LUS. The diagnosis of pneumonia was established by an expert clinician based on the recommendations of the British Thoracic Society guidelines. RESULTS: Eighty seven children with bronchiolitis were investigated. A final diagnosis of concomitant pneumonia was made in 25 patients. Sensitivity and specificity of LUS for the diagnosis of pneumonia were 100% and 83.9% respectively, with an area under-the-curve of 0.92, while CXR showed a sensitivity of 96% and specificity of 87.1%. When only consolidation > 1 cm was considered consistent with pneumonia, the specificity of LUS increased to 98.4% and the sensitivity decreased to 80.0%, with an area under-the-curve of 0.89. Cohen's kappa between pediatrician and radiologist sonologists in the first 30 patients showed an almost perfect agreement in diagnosing pneumonia by LUS (K 0.93). CONCLUSIONS: This study shows the good accuracy of LUS in diagnosing pneumonia in children with clinical bronchiolitis. When including only consolidation size > 1 cm, specificity of LUS was higher than CXR, avoiding the need to perform CXR in these patients. Added benefit of LUS included high inter-observer agreement. TRIAL REGISTRATION: Identifier: NCT03280732 . Registered 12 September 2017 (retrospectively registered).

Vertically aligned CNT-Cu nano-composite material for stacked through-silicon-via interconnects.

For future miniaturization of electronic systems using 3D chip stacking, new fine-pitch materials for through-silicon-via (TSV) applications are likely required. In this paper, we propose a novel carbon nanotube (CNT)/copper nanocomposite material consisting of high aspect ratio, vertically aligned CNT bundles coated with copper. These bundles, consisting of hundreds of tiny CNTs, were uniformly coated by copper through electroplating, and aspect ratios as high as 300:1 were obtained. The resistivity of this nanomaterial was found to be as low as ∼10(-8) Ω m, which is of the same order of magnitude as the resistivity of copper, and its temperature coefficient was found to be only half of that of pure copper. The main advantage of the composite TSV nanomaterial is that its coefficient of thermal expansion (CTE) is similar to that of silicon, a key reliability factor. A finite element model was set up to demonstrate the reliability of this composite material and thermal cycle simulations predicted very promising results. In conclusion, this composite nanomaterial appears to be a very promising material for future 3D TSV applications offering both a low resistivity and a low CTE similar to that of silicon.

Salbutamol safety in children under 2 years of age with acute wheezing: a meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the safety of short-term use of inhaled salbutamol in children under 2 years of age with acute wheezing. DATA SOURCES: Electronic databases (PubMed, Trip, MEDLINE) and the Cochrane Library were searched for studies published up to October 2022. STUDY SELECTION: The search was restricted to randomised controlled trials published in English regarding the safety of inhaled salbutamol in wheezing children under the age of 2. DATA EXTRACTION AND SYNTHESIS: The literature search strategy yielded 3532 references. The meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MAIN OUTCOMES AND MEASURES: The incidence of adverse reactions associated with inhaled salbutamol administration compared with placebo. RESULTS: A total of 24 records were included. In 7 studies involving 597 patients, inhaled salbutamol was compared with controls and no statistically significant difference in the incidence of adverse drug reactions was found between the two groups (OR 2.12, 95% CI 0.69 to 6.51; p=0.19). Salbutamol administration via nebulisation was associated with an increased incidence of adverse reactions (OR 6.76, 95% CI 2.01 to 22.71; p=0.002). None of the studies reported severe cardiac side effects that necessitated withdrawal from the study following salbutamol administration. Only one study reported a significant non-cardiac side effect (severe tremulousness) that necessitated withdrawal from therapy. CONCLUSIONS: Inhaled salbutamol can be safely used in children under 2 years of age with acute wheeze with the administration via a metered-dose inhaler being potentially safer than a nebulised formulation. Neither of the formulations was associated with severe adverse effects.

Towards graphene-based asymmetric diodes: a density functional tight-binding study.

Self-consistent charge density functional tight-binding (DFTB) calculations have been performed to investigate the electrical properties and transport behavior of asymmetric graphene devices (AGDs). Three different nanodevices constructed of different necks of 8 nm, 6 nm and 4 nm, named Graphene-N8, Graphene-N6 and Graphene-N4, respectively, have been proposed. All devices have been tested under two conditions of zero gate voltage and an applied gate voltage of +20 V using a dielectric medium of 3.9 epsilon interposed between the graphene and the metallic gate. As expected, the results of AGD diodes exhibited strong asymmetric I(V) characteristic curves in good agreement with the available experimental data. Our predictions implied that Graphene-N4 would achieve great asymmetry (A) of 1.40 at |VDS| = 0.2 V with maximum transmittance (T) of 6.72 in the energy range 1.30 eV. More importantly, while the A of Graphene-N4 was slightly changed by applying the gate voltage, Graphene-N6/Graphene-N8 showed a significant effect with their A increased from 1.20/1.03 under no gate voltage (NGV) to 1.30/1.16 under gate voltage (WGV) conditions. Our results open up unprecedented numerical prospects for designing tailored geometric diodes.

National survey conducted among Italian pediatricians examining the therapeutic management of croup.

OBJECTIVES: Practice-to-recommendations gaps exist in croup management and have not been critically investigated. This study examined the therapeutic management of croup among a national sample of Italian pediatric providers. METHODS: A survey was administered online to a sample of primary care and hospital-based pediatricians. Demographic data, perception regarding disease severity, treatment and knowledge of croup, choices of croup treatment medications, and knowledge of and adherence to treatment recommendations were compared between hospital and primary care pediatricians. Oral corticosteroids alone, oral corticosteroids with or without nebulized epinephrine and nebulized epinephrine plus oral or inhaled corticosteroids were considered the correct management in mild, moderate and severe croup, respectively. The determinants for correct management were examined using multivariate logistic regression analysis. RESULTS: Six hundred forty-nine pediatricians answered at least 50% of the survey questions and were included in the analysis. Providers reported extensive use of inhaled corticosteroids for mild and moderate croup. Recommended treatment for mild, moderate and severe croup was administered in 46/647 (7.1%), 181/645 (28.0%) and 263/643 (40.9%) participants, respectively. Provider's age and knowledge of Westley Croup Score were significant predictors for correct management of mild croup. Being a hospital pediatrician and perception of croup as a clinically relevant condition were significant for moderate croup. CONCLUSIONS: Significant differences exist between recommended guidelines and clinical practice in croup management. This study suggests wide variability in both the treatment of croup and clinical decision making strategies among hospital and primary care pediatricians. Addressing this issue could lead to noteworthy clinical and economic benefits.

Effects of cervical transcutaneous spinal direct current stimulation on spinal excitability.

OBJECTIVE: To investigate the effects of transcutaneous spinal direct current stimulation (tsDCS) on spinal cord excitability using neurophysiological methods. METHODS: Spinal cord motoneuron excitability was assessed using various neurophysiological techniques in a sham-controlled randomized experiment, which involved delivering 2 mA tsDCS and testing four different montages. Transcranial magnetic stimulation (TMS), F-waves to supramaximal ulnar nerve stimulation and somatosensory evoked potentials to upper limb nerves stimulation were measured in the participants with the electrode configuration that yielded the greatest effect, for a total of about 18 min. 18 young volunteers were recruited. RESULTS: Among the tested ones, the most promising tsDCS montage was the one with the anode placed on the 7th cervical spinous process and the cathode on the glottis. With this configuration, a significant enhancement of motor responses in the hand muscles to TMS of the contralateral hand motor area was observed during tsDCS (p<0.00001), reaching a plateau after 6 min. This facilitation rapidly declined within a few minutes after the tsDCS was stopped. CONCLUSION: Results of the different techniques suggest a possible contribution to facilitatory neuromodulation of the motoneurons at the cervical spine level. SIGNIFICANCE: The occurrence of enhanced excitability after tsDCS suggests potential application in individuals with partial corticospinal fiber impairment affecting hand motor function.

Comparison between the Viral Illness Caused by SARS-CoV-2, Influenza Virus, Respiratory Syncytial Virus and Other Respiratory Viruses in Pediatrics.

Respiratory tract infections (RTIs) are the most common infectious syndromes, primarily caused by viruses. The primary objective was to compare the illness courses between historical RTIs and recent SARS-CoV-2 infections. The study cohort consisted of RTI cases evaluated at the Pediatric Emergency Departments of Padua and Bologna, discharged or admitted with microbiologically confirmed viral RTI between 1 November 2018 and 30 April 2019 (historical period) and 1 March 2020 and 30 April 2021 (recent period). We evaluated the risk of oxygen or respiratory support, hospitalization, antibiotic therapy, and complications among different viral infections. The odds ratio (OR) and the 95% confidence intervals (CIs) were estimated through mixed-effect logistic regression models, including a random intercept on the individual and hospital. We identified 767 RTIs: 359 in the historical period compared with 408 SARS-CoV-2 infections. Infections of SARS-CoV-2 had a lower risk of being admitted (OR 0.04, 95% CI 0.03-0.07), receiving respiratory support (OR 0.19, 95% CI 0.06-0.58), needing antibiotic therapy (OR 0.35, 95% CI 0.22-0.56) and developing complications (OR 0.27, 95% CI 0.14-0.51) compared to all other viral RTIs. COVID-19 in children is clinically similar to other viral RTIs but is associated with a less severe infection course. Thus, most prevention strategies implemented for SARS-CoV-2 should still be considered during RSV and Influenza epidemics.

Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation.

OBJECTIVE: To evaluate the analgesic superiority and the safety equivalence of continuous fentanyl infusions versus fentanyl boluses in preterm infants on mechanical ventilation. STUDY DESIGN: In this multicenter, double-blind, randomized controlled trial, mechanically ventilated newborns (≤ 32(+6) weeks gestational age) were randomized to fentanyl (continuous infusion of fentanyl plus open-label boluses of fentanyl) or placebo (continuous infusion of placebo plus open-label boluses of fentanyl). The primary endpoint was analgesic efficacy, as evaluated by the Echelle Douleur Inconfort Nouveau-Né (EDIN) and Premature Infant Pain Profile scales. Safety variables were evaluated as well. RESULTS: Sixty-four infants were allocated to the fentanyl group, and 67 were allocated to the placebo group. The need for open-label boluses of fentanyl was similar in the 2 groups (P = .949). EDIN scores were comparable in the 2 groups; 65 of 961 (6.8%) EDIN scores were >6 in the fentanyl group and 91 of 857 (10.6%) in the placebo group (P = .003). The median Premature Infant Pain Profile score was clinically and statistically higher in the placebo group compared with the fentanyl group on days 1, 2, and 3 of treatment (P < .05). Mechanical ventilation at age 1 week was required in 27 of 64 infants in the fentanyl group (42.2%), compared with 17 of 67 infants in the placebo group (25.4%) (P = .042). The first cycle of mechanical ventilation was longer and the first meconium passage occurred later in the fentanyl group (P = .019 and .027, respectively). CONCLUSION: In very preterm infants on mechanical ventilation, continuous fentanyl infusion plus open-label boluses of fentanyl does not reduce prolonged pain, but does reduce acute pain and increase side effects compared with open-label boluses of fentanyl alone.