We aimed to evaluate the efficacy of combined (ibuprofen+paracetamol) medical therapy in cases of persistent haemodynamically significant patent ductus arteriosus that are resistant to standard medical monotherapy (ibuprofen and/or paracetamol) in this retrospective multi-centre study.

The combined therapy included the administration of 15mg/kg/dose of paracetamol every 6 h for 3 days and ibuprofen at an initial dose of 10mg/kg/dose followed by 5 mg/kg/dose every 24 h. After 2 days following the administration of the last dose, the researchers evaluated the efficacy of combined treatment by conducting an echocardiographic examination.

Of all 42 patients who received combined therapy, 37 (88.1%) patients exhibited closure of the haemodynamically significant patent ductus arteriosus without requiring surgical ligation. Patients who did not respond to combined therapy had a higher mean birth weight and gestational age compared to those who responded (p < 0.05).

The researchers believe the success of ibuprofen and paracetamol in haemodynamically significant patent ductus arteriosus treatment may be due to their synergistic efficacy and inhibition of the prostaglandin synthesis pathway through different enzymes. The results of our retrospective trial suggest that combination therapy with paracetamol and ibuprofen can be attempted when monotherapy is unsuccessful in treating haemodynamically significant patent ductus arteriosus, especially in centres without a surgical department.

Vascular endothelial growth factor is critically involved in ductus arteriosus closure. Polymorphisms in the vascular endothelial growth factor gene have been associated with several diseases in neonates and adults.

Herein, we investigated if vascular endothelial growth factor polymorphism rs2010963 status is associated with patent ductus arteriosus incidence and/or pharmacological treatment success.

We assessed rs2010963 status in 814 preterm infants (<1500 g birth weight) by means of restriction fragment length polymorphism analysis. DNA samples were obtained from dry-spot cards used for the German national newborn screening program. Clinical data were obtained by retrospective chart review.

We could not find any statistically significant difference in the incidence of patent ductus arteriosus depending on vascular endothelial growth factor rs2010963 polymorphism status. Furthermore, no statistically significant associations between vascular endothelial growth factor polymorphism rs2010963 status and cyclooxygenase inhibitor treatment success were observed.

Our results indicate that there is no association between vascular endothelial growth factor polymorphism rs2010963 status and the occurrence of patent ductus arteriosus or the response to cyclooxygenase inhibitor treatment in a large cohort of preterm infants. Additional studies are needed to determine the role of genetic factors on patent ductus arteriosus incidence and treatment response.

A double-blinded, randomised, placebo-controlled trial was conducted to determine whether routine pre-operative analgesia is beneficial in reducing post-operative ear pain following bilateral myringotomy and tube placement.

Forty-five children (aged 3–15 years) were randomised to receive either pre-operative analgesics (paracetamol and ibuprofen) (n = 21) or placebo (n = 24). All children underwent sevoflurane gas induction with intranasal fentanyl (2 mcg/kg) to reduce the incidence of emergence agitation. Post-operative pain scores were measured using the Wong-Baker Faces Pain Rating Scale. Median pain scores taken 90 minutes post-surgery, and the highest pain score recorded prior to 90 minutes, were analysed.

There were no statistical differences between the median pain scores at 90 minutes or subsequent need for rescue analgesia. Emergence agitation did not occur in any child. Inadvertent ear trauma, use of an intravenous cannula or airway adjunct did not affect pain scores.

Routine pre-operative analgesia does not reduce pain scores in the early post-operative period. Simple analgesics are effective for rescue analgesia in the minority of cases.

Cyclooxygenase inhibitors are widely applied to facilitate ductal closure in preterm infants. The mechanisms that lead to patent ductus arteriosus closure are incompletely understood. Vascular endothelial growth factor plays pivotal roles during ductal closure and remodelling.

The aim of this study was to investigate the effects of ibuprofen and indomethacin on the expression of vascular endothelial growth factor and its receptors in a primary rat ductus arteriosus endothelial cell culture.

Protein expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 and 2 was confirmed in rat ductus arteriosus and aorta by immunofluorescence staining. Fetal rat endothelial cells were isolated from ductus arteriosus and aorta using immunomagnetic cell sorting and treated with ibuprofen or indomethacin. mRNA expression levels were assessed by quantitative polymerase chain reaction analysis.

In ductal endothelial cells, ibuprofen significantly induced vascular endothelial growth factor and its receptor 2, but not receptor 1, whereas indomethacin did not alter the expression levels of the vascular endothelial growth factor system. In contrast, ibuprofen significantly induced vascular endothelial growth factor and its receptors 1 and 2 in aortic endothelial cells, whereas indomethacin only induced vascular endothelial growth factor receptor 2.

Our results indicate differential effects of ibuprofen and indomethacin on the expression levels of the vascular endothelial growth factor system in ductus arteriosus endothelial cells. In addition, vessel-specific differences between ductal and aortic endothelial cells were found. Further in vivo studies are needed to elucidate the biological significance of these findings.

The aim of this study was to identify inter-centre differences in persistent ductus arteriosus treatment and their related outcomes.

We carried out a retrospective, multicentre study including infants between 24+0 and 27+6 weeks of gestation in the period between 2010 and 2011. In all centres, echocardiography was used as the standard procedure to diagnose a patent ductus arteriosus and to document ductal closure.

In total, 367 preterm infants were included. All four participating neonatal ICU had a comparable number of preterm infants; however, differences were observed in the incidence of treatment (33–63%), choice and dosing of medication (ibuprofen or indomethacin), number of pharmacological courses (1–4), and the need for surgical ligation after failure of pharmacological treatment (8–52%). Despite the differences in treatment, we found no difference in short-term morbidity between the centres. Adjusted mortality showed independent risk contribution of gestational age, birth weight, ductal ligation, and perinatal centre.

Using benchmarking as a tool identified inter-centre differences. In these four perinatal centres, the factors that explained the differences in patent ductus arteriosus treatment are quite complex. Timing, choice of medication, and dosing are probably important determinants for successful patent ductus arteriosus closure.

Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen.

This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48–96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel’s method.

This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups.

Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

We compared pain severity and time to resumption of activities in patients with cervical strains treated with a nonsteroidal anti-inflammatory drug (NSAID), a centrally acting muscle relaxant or both.

We performed a double-blinded, randomized controlled trial of adults with cervical strains from motor vehicle collisions or from falls who presented to a suburban academic emergency department (ED). Patients were randomly assigned to receive ibuprofen 800 mg, cyclobenzaprine 5 mg or both, 3 times daily as needed for up to 7 days. Outcome measures included a pain score on a 100-mm visual analog scale, pain relief scores, the time to resumption of normal activities, the use of rescue medications, and adverse outcomes. We used repeated-measures analysis of variance to compare pain relief over time. Our sample size of 20 patients in each group had a power of 80% to detect a difference of 15 mm in pain relief scores between the highest and lowest groups.

We randomly assigned 61 patients to receive ibuprofen (n = 20), cyclobenzaprine (n = 21) or both (n = 20). Mean (standard deviation) age was 34 (11) years; 58% were women and 72% were white. Although pain scores improved over time in all groups, there were no significant differences between the groups in any of the outcome measures. The rate of adverse events was also similar between groups.

Our study suggests that there is little benefit to routinely using or adding cyclobenzaprine to NSAIDs for ED patients with acute cervical strain.

We present a rare case of oesophageal perforation following ingestion of over-the-counter ibuprofen capsules.

Case report and literature review of pill oesophagitis.

A previously well, 18-year-old man presented with sudden onset, severe, retrosternal pain, dysphagia and odynophagia following ingestion of over-the-counter ibuprofen capsules. Plain X-ray films and a contrast-enhanced computed tomography scan indicated the diagnosis. The patient was successfully treated with non-operative management.

To our knowledge, this is the first report in the world literature concerning oesophageal perforation with ibuprofen. We discuss pill-induced oesophageal injury and its prevention. Manufacturers, clinicians and patients can all take steps to avoid this potentially life-threatening complication.