Male/female differences in indomethacin effects in preterm infants

To test whether indomethacin prophylaxis has sex-mediated effects on severe intraventricular hemorrhage (grade III and IV) and on long-term outcomes in extremely-low-birth-weight infants. A secondary analysis was performed in the entire "Trial of Indomethacin Prophylaxis in Preterms study" cohort. The results suggest a weak differential treatment effect of indomethacin by sex.     

Early prediction of poor outcome in extremely low birth weight infants by classification tree analysis

OBJECTIVE: To predict death or neurodevelopmental impairment (NDI) in extremely low birth weight infants by classification trees with recursive partitioning and automatic selection of optimal cut points of variables. STUDY DESIGN: Data from the Trial of Indomethacin Prophylaxis in Preterms were randomly divided into development (n=784) and validation sets (n=262). Three models were developed for the combined outcome of death (8 days to 18 months) or NDI (cerebral palsy, cognitive delay, deafness, or blindness at 18 months corrected age): antenatal: antenatal data; early neonatal: antenatal+first 3 days data; and first week: antenatal, first 3 days, and 4th to 8th days data. Decision trees were tested on the validation set. RESULTS: Variables associated with death/NDI in each model were: Antenatal: Gestation01 mL/kg/d. First week: Birth weight3 mL/kg/d. Birth weight>787 g: cranial echodense intraparenchymal lesion and transfusion>1 mL/kg/d. Correct classification rates were 61% to 62% for all models. CONCLUSIONS: The ability to predict long-term morbidity/death in extremely low birth weight infants does not improve significantly over the first week of life. Effects of different variables depend on age.     

The role of twinning in sustainable care for children with cancer: A TIPPing point? SIOP PODC Working Group on Twinning,Collaboration, and Support

With the World Health Organization (WHO) Global Initiative for Childhood Cancer, there is renewed interest in sustainable interventions to improve childhood cancer care in low‐/middle‐income countries (LMICs). Practitioners in LMICs have traditionally practiced “twinning,” i.e., targeted international pediatric oncology partnerships (TIPPs) between one or more institutions in a high‐income country (HIC) and an LMIC, to improve care for children with cancer in the latter. The International Society of Paediatric Oncology Committee for Paediatric Oncology in Developing Countries Working Group on Twinning, Collaboration, and Support reviewed guidelines from https://cancerpointe.com and the current literature, gathered input from practitioners in LMICs, and in this article discuss the role of TIPPs in the WHO initiative.     

The receptor-bound conformation of H-Tyr-Tic-(Phe-Phe)-OH-related δ-opioid antagonists contains all trans peptide bonds

Two different models for the receptor-bound conformation of δ-opioid peptide antagonists containing the N-terminal dipeptide segment H-Tyr-Tic (Tic = 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) have been proposed. Both models are based on spatial overlap of the Tyr and Tic² aromatic rings and N-terminal amino group with the corresponding aromatic rings and nitrogen atom of the nonpeptide δ-antagonist naltrindole. However, in one model the peptide bond between the Tyr and Tic² residues assumes the trans conformation, whereas in the other it is in the cis conformation. To distinguish between these two models, we prepared the two peptides H-Tyrψ[CH₂NH]. Tic-Phe-Phe-OH and H-Tyrψ[CH₂NH]. MeTic-Phe-Phe-OH (MeTic = 3-methyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) in which a cis peptide bond between the Tyr and Tic (or MeTic) residues is sterically forbidden. Both compounds turned out to be moderately potent δ-opioid antagonists in the mouse vas deferens assay. A molecular mechanics study performed with both peptides resulted in low-energy conformations in which the torsional angle (“ω₁”) of the reduced peptide bond between Tyr and Tic (or MeTic) had a value of 180°(trans conformation) and which were in good agreement with the proposed model with all trans peptide bonds. Furthermore, this study confirmed that neither of these two peptides could assume low-energy conformations in which “ω₁” had a value of 0°(cis conformation). Conformers with that same bond in the gauche- conformation (“ω₁”= -60“) were also identified, but were higher in energy and showed no spatial overlap with naltrindole. On the basis of these results it is concluded that the receptor-bound conformation of δ-peptide antagonists containing an N-terminal H-Tyr-Tic-dipeptide segment must have all trans peptide bonds. © Munksgaard 1998.     

Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP)

OBJECTIVES: To determine the risk of bronchopulmonary dysplasia (BPD) in subgroups of infants with and without patent ductus arteriosus (PDA) who were randomized to indomethacin prophylaxis or placebo, and to examine whether adverse drug effects on edema formation and oxygenation may explain why indomethacin prophylaxis does not reduce BPD. STUDY DESIGN: We studied 999 extremely low birth weight infants who participated in the Trial of Indomethacin Prophylaxis in Preterms (TIPP) and who survived to a postmenstrual age of 36 weeks. RESULTS: The incidence of BPD in the 2 subgroups of infants with PDA was 52% (55/105) after indomethacin prophylaxis and 56% (137/246) after placebo. In contrast, rates of BPD in the 2 subgroups without a PDA were 43% (170/391) after indomethacin prophylaxis and 30% (78/257) after placebo (P [interaction] = .015). Logistic regression analysis with adjustment for prognostic baseline factors showed that adverse and independent effects of indomethacin prophylaxis on the need for supplemental oxygen and on weight loss by the end of the first week of life may increase the risk of BPD in infants without PDA. CONCLUSIONS: Harmful side effects on oxygenation and edema formation may explain why indomethacin prophylaxis does not prevent BPD even though it reduces PDA.     

Quality of life after open versus laparoscopic preperitoneal mesh repair for unilateral inguinal hernias

BackgroundBoth the open transinguinal preperitoneal repair (TIPP) and the laparoscopic total extraperitoneal mesh repair (TEP) show excellent outcomes. Direct comparative data between these 2 preperitoneal techniques is lacking. The aim of this study was to assess postoperative outcomes and quality of life (QoL) for these open and laparoscopic preperitoneal repair techniques.MethodsBetween 2014 and 2016, 204 male patients underwent unilateral inguinal hernia repair through TIPP (n = 135) or TEP (n = 69). Data recorded include demographic profile, preoperative and intraoperative variables, postoperative complications and postoperative quality of life. Two validated hernia-specific QoL questionnaires, the Carolinas Comfort Scale (CCS) and the European Registry for Abdominal Wall Hernias Quality of Life score (EuraHS QoL) were used to assess postoperative QoL.ResultsThe TIPP group consisted of 135 patients, the TEP group of 69 patients. The mean age of patients was significantly higher in TIPP (64.07 ± 17.10 years) than in TEP (59.0 ± 15.53 years) (p = 0.022). A total of 96 patients (47.1%) responded to our invitation for longterm follow-up: 58 in the TIPP group (43%) and 38 in the TEP group (55.1%). There was no difference in mean follow-up time between the surgical procedure and filling in the questionnaires: 37.4 ± 12.8 months for TIPP and 33.5 ± 11.3 months for TEP group (p = 0.13). No significant differences in quality of life were found between TIPP and TEP for all explored domains.ConclusionTIPP and TEP show equivalent results considering postoperative quality of life. Compared to existing literature on mesh repair for unilateral inguinal hernias, we may conclude that the preperitoneal location of the mesh probably is a more decisive factor for quality of life than the surgical approach used.