Longitudinal trends in domperidone dispensing to mothers of very preterm infants and its association with breast milk feeding at infant discharge: a retrospective study.

OBJECTIVE: This study aims: (a) to evaluate patterns of domperidone dispensing to mothers of very preterm (<32 weeks gestation) infants born before and after 2014 when international recommendations were made to limit its use and (b) to examine characteristics associated with domperidone dispensing and impacts on breast milk feeding rates at infant hospital discharge. DESIGN: Retrospective audit using linked electronic medical records and hospital pharmacy records. SETTING: Tertiary-referral neonatal intensive care unit at the Women's and Children's Hospital in South Australia. PATIENTS: Mothers of preterm infants admitted to neonatal intensive care from January 2004 to December 2018. MAIN OUTCOME MEASURES: Rate of domperidone dispensing compared pre-2014 and post-2014 recommendations using interrupted time series analyses, and breast milk feeding rates at infant discharge based on domperidone treatment status, adjusted for other factors known to influence breast milk production. RESULTS: Overall, domperidone was dispensed to 691 (41%) of 1688 mothers. Prior to 2014 recommendations, the proportion of women dispensed domperidone was stable. Following the recommendations, there was a significant reduction in trend (-2.55% per half year, 95% CI -4.57% to -0.53%;), reflecting less domperidone dispensing.Breast milk feeding rates at discharge remained consistently lower in infants of women dispensed domperidone than those who were not (adjusted OR 0.58, 95% CI 0.45 to 0.75). CONCLUSION: Domperidone dispensing in mothers of hospitalised very preterm infants has declined over time following international regulatory warnings. Breast milk feeding rates remain lower in mothers prescribed domperidone, suggesting further research is needed to optimise lactation support for mothers of very preterm infants.

Clinical allograft of a calcaneal tendon in a rhesus macaque (Macaca mulatta).

A 5.5-y-old male rhesus monkey (Macaca mulatta) housed in an outdoor field cage presented for severe trauma involving the left calcaneal tendon. Part of the management of this wound included an allograft of the calcaneal tendon from an animal that was euthanized for medical reasons. This case report describes the successful medical and surgical management of a macaque with a significant void of the calcaneal tendon. To our knowledge, this report is the first description of a successful tendon allograft in a rhesus macaque for clinical purposes.

Validation of a body condition scoring system in rhesus macaques (Macaca mulatta): inter- and intrarater variability.

Body condition scoring (BCS) is a subjective semiquantitative method of assessing body fat and muscle. Scoring systems use a scale in which the midrange represents optimal body condition, lower values represent lean to emaciated conditions, and higher values indicate excessive body fat. A valid BCS system is clearly described, relevant to the species, shows agreement within and between raters, and is consistent with objective measures. The goal of the current study was to assess intra- and interrater variability of a BCS system that uses a 1-to-5 scale and entails the palpation of key anatomic sites (hips, spine, pelvis, thorax, and abdomen) to assess prominence of bony structures, muscle mass, and subcutaneous fat. To assess interrater variability, 4 raters independently assessed BCS in 616 rhesus macaques (Macaca mulatta) in 4 age groups: infant, younger than 1 y; juvenile, 1 to 4 y; subadult, 4 to 7 y; and adult, 7 to 17 y. To assess intrarater variability, each rater independently reevaluated a subset of adult macaques (n = 15) within 2 wk of initial evaluation. A weighted κ score was used to analyze intra- and interrater variability. Agreement between raters was highest for subadult and adult macaques, intermediate for juveniles, and least for infants. Intrarater agreement was high for all raters except one, for which it was moderate. Our results suggest that raters applied the BCS system most consistently to adult and subadult macaques and less so to juvenile and infant animals. However, the percentage agreement between raters to within one half of a score unit increased markedly when raters scored infants in the context of 'as is' rather than 'ideal for age.'

Validation of a body condition scoring system in rhesus macaques (Macaca mulatta): assessment of body composition by using dual-energy X-ray absorptiometry.

Body condition scoring (BCS) is a subjective semiquantitative method of assessing body fat and muscle by palpation of key anatomic features. A previously published BCS system for rhesus macaques (Macaca mulatta) uses a scale comprising both whole and half units, in which the midrange represents optimal body condition (3.0), lower values represent emaciated to lean conditions (1.0 to 2.0), and higher values (4.0 to 5.0) indicate excessive body fat. A valid BCS system is well described, relevant to the species, has agreement within and between raters, and is consistent with objective measures. Here we correlate the subjective BCS assigned during physical exam with percentage body fat as determined by dual-energy X-ray absorptiometry (DEXA). Adult rhesus monkeys from an indoor-housed breeding colony were evaluated by the veterinary staff and assigned to 1 of 9 BCS score groups to give a minimum of 6 animals in each group. DEXA was used to obtain objective body composition measurements for macaques in each BCS group. Animals in the 'optimal' BCS group (3.0) had 25% body fat on average. Each full unit change in BCS was associated with an approximate 10% change in body fat percentage for macaques in the 2.0-to-5.0 BCS range. Absolute body fat in animals with BCS of 1.0 or 1.5 may be too low for accurate assessment by DEXA.

Pharmacokinetics of oxymorphone in titi monkeys (Callicebus spp.) and rhesus macaques (Macaca mulatta).

Oxymorphone is a pure µ-opioid receptor agonist that is commonly used in nonhuman primate medicine and surgery to minimize pain ranging in intensity from moderate to severe. We compared pharmacokinetic profiles and physiologic and behavioral responses to oxymorphone between titi monkeys (Callicebus spp.) and rhesus macaques (Macaca mulatta). Titi monkeys (n = 4) and rhesus macaques (n = 4) were injected intravenously with either a bolus of 0.075 mg/kg oxymorphone or placebo on multiple occasions, with a minimal washout period of 14 d between trials. Blood collection was limited to no more than 3 samples per trial, with samples collected at multiple time points until 10 h after injection. Collection periods, animal order, and testing day were randomized. In addition, macaques underwent a single serial collection at all time points to validate study design. A 2-compartment model best described the disposition of oxymorphone in both species. Clearance was faster in macaques than titi monkeys, in which terminal half-life was longer. Statistically significant physiologic differences were found between species and between treatments within species. Apart from these effects, oxymorphone did not significantly change physiologic parameters over time. After oxymorphone treatment, macaques demonstrated behaviors reflecting pruritis, whereas titi monkeys exhibited sedation. Despite its mild side effects, we recommend the consideration of oxymorphone for pain management protocols in both Old and New World nonhuman primates.

Reduced TCOF1 mRNA level in a rhesus macaque with Treacher Collins-like syndrome: further evidence for haploinsufficiency of treacle as the cause of disease.

Mutations in the human gene TCOF1 cause a mandibulofacial dysostosis known as Treacher Collins syndrome (TCS). An infant rhesus macaque (Macaca mulatta) that displayed the TCS phenotype was identified at the California National Primate Research Center. The TCOF1 coding region was cloned from a normal rhesus macaque and sequenced. The rhesus macaque homolog of TCOF1 is 91.6% identical in cDNA sequence and 93.8% identical in translated protein sequence compared to human TCOF1. Sequencing of TCOF1 in the TCS-affected rhesus macaque showed no mutations within the coding region or splice sites; however, real-time quantitative PCR showed an 87% reduction of spleen TCOF1 mRNA level in the TCS affected macaque when compared with normal macaque spleen.

Development of a body condition scoring system for nonhuman primates using Macaca mulatta as a model.

The nutritional status of individual monkeys in research projects is an important yet sometimes overlooked variable that complicates the interpretation of research findings. The authors offer a framework for scoring fatness and muscularity in a semiquantitative manner without special equipment and in a way that could easily be accomplished during a routine physical examination. Body condition scoring can be used to assess the health of individual animals as well as determine nutritional adequacy within groups of animals.