A longitudinal observational study on the epidemiology of painful procedures and sucrose administration in hospitalized preterm neonates.

Although sucrose is widely administered to hospitalized infants for single painful procedures, total sucrose volume during the entire neonatal intensive care unit (NICU) stay and associated adverse events are unknown. In a longitudinal observation study, we aimed to quantify and contextualize sucrose administration during the NICU stay. Specifically, we investigated the frequency, nature, and severity of painful procedures; proportion of procedures where neonates received sucrose; total volume of sucrose administered for painful procedures; and incidence and type of adverse events. Neonates <32 weeks gestational age at birth and <10 days of life were recruited from four Canadian tertiary NICUs. Daily chart reviews of documented painful procedures, sucrose administration, and any associated adverse events were undertaken. One hundred sixty-eight neonates underwent a total of 9093 skin-breaking procedures (mean 54.1 [±65.2] procedures/neonate or 1.1 [±0.9] procedures/day/neonate) during an average NICU stay of 45.9 (±31.4) days. Pain severity was recorded for 5399/9093 (59.4%) of the painful procedures; the majority (5051 [93.5%]) were heel lances of moderate pain intensity. Sucrose was administered for 7839/9093 (86.2%) of painful procedures. The total average sucrose volume was 5.5 (±5.4) mL/neonate or 0.11 (±0.08) mL/neonate/day. Infants experienced an average of 7.9 (±12.7) minor adverse events associated with pain and/or sucrose administration that resolved without intervention. The total number of painful procedures, sucrose volume, and incidence of adverse events throughout the NICU stay were described addressing an important knowledge gap in neonatal pain. These data provide a baseline for examining the association between total sucrose volume during NICU stay and research on longer-term behavioral and neurodevelopmental outcomes.

The effectiveness of repeated sucrose for procedural pain in neonates in a longitudinal observational study.

Goal: To determine the analgesic effectiveness of repeated sucrose administration for skin-breaking (SB) procedures over the Neonatal Intensive Care Unit (NICU) hospitalization of preterm infants. Methods: Longitudinal observational study, conducted in four level III Canadian NICUs. Eligible infants were <32 weeks gestational age at birth, and <10 days of life at enrollment. Infants received 24% sucrose (0.12 ml) prior to all painful procedures. The Premature Infant Pain Profile - Revised (PIPP-R) was used at 30 and 60 seconds after a medically-required SB procedure as soon as possible after enrollment and weekly up to three additional times for scheduled procedures. Results: 172 infants (57.3% male, gestational age 28.35 (±2.31) weeks) were included. The mean 30 s PIPP-R scores were 6.11 (±3.68), 5.76 (±3.41), 6.48 (±3.67), and 6.81 (±3.69) respectively; there were no statistically significant interactions of study site by time (p = 0.31) or over time (p = 0.15). At 60 s, mean PIPP-R scores were 6.05 (±4.09), 5.74 (±3.67), 6.19 (±3.7), and 5.99 (±3.76) respectively; there were no study site by time interactions (p = 0.14) or differences over time (p = 0.52). There was a statistically significant site difference in the effectiveness of sucrose at 30 and 60 seconds (p < 0.01). Conclusions: Consistently low PIPP-R scores following a skin-breaking procedure indicated that the analgesic effectiveness of the minimal dose of sucrose was sustained over time in the NICU. Further research is required to determine the optimal combination of sucrose and other pain management strategies to improve clinical practice and the impact of consistent use of repeated use of sucrose on neurodevelopment.

Effectiveness of parental education about pain in the neonatal period on knowledge, attitudes, and practices: A systematic review and meta-analysis.

Background: Despite the availability of effective, safe, and feasible pain management strategies, infant pain remains undertreated. Parents can play a key role in advocating for or delivering pain management strategies if they are educated. To date, a quantitative synthesis of the effectiveness of parental education about pain management in the neonatal period has not been performed. Objective: To systematically review the effectiveness of parental education during the neonatal period on pain management in infancy. Methods: MEDLINE, EMBASE, PsycInfo, CINAHL, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) and non-randomized trials (NRTs) that evaluated parental education with respect to pain management during the neonatal period in any setting from inception to February 2021. Screening of article titles and abstracts and data extraction were performed in duplicate. The risk of bias was assessed using the Cochrane Risk Bias Tool 2.0 and the Risk of Bias in Non-randomized Studies of Interventions for RCTs and NRTs, respectively. As per the GRADE methodology, critically important and important outcomes were identified. Critically important outcomes included utilization of pain management strategies and infant pain. Important outcomes included parental knowledge about pain mitigation strategies, parental attitudes, compliance with painful procedures, procedure outcomes, and safety. Data were combined and presented as relative risk (RR) or mean or standardized mean difference (MD or SMD) with 95% confidence interval (CI). Results: Of the six studies eligible for inclusion, four studies were RCTs and two studies were NRTs. Written information and/or video were used to deliver parental education during the neonatal period in hospital settings in all studies. Four studies (two RCTs and two NRTs) reported on critically important outcomes. The risk of bias was low for the two RCTs and moderate to serious for the two NRTs. Utilization of pain management strategies was assessed for heel lance in the first 48 hours of life in two studies and for vaccine injection at 2 to 6 months of life in two studies. Higher utilization rate for pain management strategies was reported in the pain education group in three studies (RR 1.15, 95% CI 1.04, 1.26; N=2712). There was no difference in the mean number of pain management strategies used in one NRT tracking utilization tracking utilization as continuous data (MD 0.20, 95% CI -0.01, 0.41; N=178). Parent-reported infant pain scores were lower in the pain education group in one RCT (MD -0.16, 95% CI -0.27, -0.06; N=1615). The quality of evidence for the outcome of utilization of pain management strategies was very low while for the outcome of infant pain the quality of evidence was moderate. Five studies (3 RCTs and 2 NRTs) reported on important outcomes. The risk of bias was low for two RCTs and high for one RCT and moderate to serious for the two NRTs. Parental knowledge about pain management strategies (SMD 0.54, 95% CI 0.26, 0.82), parental confidence in their ability to manage pain (SMD 0.24, 95% CI 0.14, 0.34), parental satisfaction with education (MD 1.18, 95% CI 0.84, 1.52) and parental satisfaction with pain management (RR 1.05. 95% CI 1.01, 1.08) were increased in the pain education group. None of the included studies reported on procedural outcomes. No adverse events with the pain education nor the use of pain management interventions were reported in one study. Conclusions: Parental education in the neonatal period was effective in increasing utilization of pain management strategies during painful procedures. Reduction of pain in infants is based on one study of moderate quality. Furthermore, parental education increased parental knowledge about pain management strategies, confidence in their ability to manage infant pain, and satisfaction with the education and pain management. Parental pain education should be incorporated into postnatal care.

The Effect of Music and White Noise on Electroencephalographic (EEG) Functional Connectivity in Neonates in the Neonatal Intensive Care Unit.

The purpose of this study is to investigate whether listening to music and white noise affects functional connectivity on scalp electroencephalography (EEG) in neonates in the neonatal intensive care unit.Nine neonates of ≥34 weeks' gestational age, who were already undergoing clinical continuous EEG monitoring in the neonatal intensive care unit, listened to lullaby-like music and white noise for 1 hour each separated by a 2-hour interval of no intervention. EEG segments during periods of music, white noise, and no intervention were band-pass filtered as delta (0.5-4 Hz), theta (4-8 Hz), lower alpha (8-10 Hz), upper alpha (10-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz). Synchronization likelihood was used as a measure of connectivity between any 2 electrodes.In theta, lower alpha, and upper alpha frequency bands, the synchronization likelihood values yielded statistical significance with sound (music, white noise and no intervention) and with edge (between any 2 electrodes) factors. In theta, lower alpha, and upper alpha frequency bands, statistical significance was obtained between music and white noise (t = 3.12, 3.32, and 3.68, respectively; P < .017), and between white noise and no intervention (t = 4.51, 3.09, and 2.95, respectively, P < .017). However, there was no difference between music and no intervention.Although limited by a small sample size and the 1-time only auditory intervention, these preliminary results demonstrate the feasibility of EEG connectivity analyses even at bedside in neonates on continuous EEG monitoring in the neonatal intensive care unit. They also point to the possibility of detecting significant changes in functional connectivity related to the theta and alpha bands using auditory interventions.

Hemodynamic Instability in Hypoxic Ischemic Encephalopathy: More Than Just Brain Injury-Understanding Physiology, Assessment, and Management.

Hypoxic-ischemic encephalopathy (HIE) can have both transient and long-lasting effects on the neonate, including neurologic, renal, cardiac, hepatic, and hematologic. Both the disease process and the treatment option of therapeutic hypothermia can result in hemodynamic instability. Understanding the effects of HIE on the neonatal myocardium, pulmonary vascular bed, and the cardiac dysfunction that can occur is key to managing infants with HIE. This article focuses on causes of hemodynamic instability in neonates following perinatal asphyxia and how to recognize hemodynamic compromise. It reviews the underlying pathophysiology and associated management strategies to improve hemodynamics and potentially improve outcomes.

Glucose Homeostasis and the Neonatal Brain: A Sweet Relationship.

Glucose is the primary substrate for energy metabolism in the brain and although the brain is dependent on a constant glucose supply for normal function, both local energy stores and the supply of alternate substrates are limited. In utero, the placenta provides a continuous supply of glucose to the fetus while transition to extrauterine life marks an abrupt change in substrate delivery and a major change in glucose metabolism where insufficiencies and disruptions can occur. Hypoglycemia is one of the most common biochemical disturbances in the neonatal period, affecting a wide range of neonates. Prolonged or persistent low plasma glucose concentrations can lead to neonatal brain injury and abnormal neurological outcomes. This article discusses fetal and neonatal metabolic adaptation, the physiology of glucose homeostasis, hypoglycemic brain injury (HBI), and neurodevelopmental long-term outcomes.

Metasynthesis of Factors That Influence Parents' Participation in Pain Management for Their Infants in the NICU.

OBJECTIVE: To metasynthesize the results of qualitative studies on the factors that affect parents' participation in pain management for their infants during procedures in the NICU. DATA SOURCES: We conducted a literature search for articles published from 1976 through November 2019 using MeSH terminology in the following databases: MEDLINE, CINAHL Plus, EMBASE, PubMed, PsycINFO, Cochrane, Scopus, and Web of Science. All qualitative studies in which researchers explored parental participation and education in the NICU were included. STUDY SELECTION: A total of 29,937 articles were returned. Once we removed duplicates and limited results to qualitative studies, 48 articles remained. We excluded 41 articles because the studies reported were not conducted in NICUs, involved neonatal palliative care, or were review or opinion articles. We included seven articles for review. DATA EXTRACTION: Two authors reviewed all articles using the Critical Appraisal Skills Programme tool to assess study quality and independently scored each study. We reviewed and extracted authors, publication date, type of study, sample size, results, themes, and quotes and included these data elements in the analysis. DATA SYNTHESIS: We used a thematic synthesis technique to review the qualitative data, entered codes into NVivo software, and compared codes to create descriptive themes. From these descriptive themes, we generated four analytic themes: Learning to Parent a Hospitalized Infant, Stress and Anxiety, Health Care Providers as Gatekeepers, and NICU Environment. CONCLUSION: The four themes identified in this qualitative metasynthesis represent the factors that affect parents' abilities to participate in their infants' pain management. Further research is recommended to develop interventions that address these factors to optimize parents' participation in pain management for their infants during procedures in the NICU.

Genome-wide survey of cytochrome P450 genes in the salmon louse Lepeophtheirus salmonis (Krøyer, 1837).

BACKGROUND: The salmon louse (Lepeophtheirus salmonis) infests farmed and wild salmonid fishes, causing considerable economic damage to the salmon farming industry. Infestations of farmed salmon are controlled using a combination of non-medicinal approaches and veterinary drug treatments. While L. salmonis has developed resistance to most available salmon delousing agents, relatively little is known about the molecular mechanisms involved. Members of the cytochrome P450 (CYP) superfamily are typically monooxygenases, some of which are involved in the biosynthesis and metabolism of endogenous compounds, while others have central roles in the detoxification of xenobiotics. In terrestrial arthropods, insecticide resistance can be based on the enhanced expression of CYPs. The reported research aimed to characterise the CYP superfamily in L. salmonis and assess its potential roles in drug resistance. METHODS: Lepeophtheirus salmonis CYPs were identified by homology searches of the genome and transcriptome of the parasite. CYP transcript abundance in drug susceptible and multi-resistant L. salmonis was assessed by quantitative reverse transcription PCR, taking into account both constitutive expression and expression in parasites exposed to sublethal levels of salmon delousing agents, ecdysteroids and environmental chemicals. RESULTS: The above strategy led to the identification of 25 CYP genes/pseudogenes in L. salmonis, making its CYP superfamily the most compact characterised for any arthropod to date. Lepeophtheirus salmonis possesses homologues of a number of arthropod CYP genes with roles in ecdysteroid metabolism, such as the fruit fly genes disembodied, shadow, shade, spook and Cyp18a1. CYP transcript expression did not differ between one drug susceptible and one multi-resistant strain of L. salmonis. Exposure of L. salmonis to emamectin benzoate or deltamethrin caused the transcriptional upregulation of certain CYPs. In contrast, neither ecdysteroid nor benzo[a]pyrene exposure affected CYP transcription significantly. CONCLUSIONS: The parasite L. salmonis is demonstrated to possess the most compact CYP superfamily characterised for any arthropod to date. The complement of CYP genes in L. salmonis includes conserved CYP genes involved in ecdysteroid biosynthesis and metabolism, as well as drug-inducible CYP genes. The present study does not provide evidence for a role of CYP genes in the decreased susceptibility of the multiresistant parasite strain studied.

Nonpharmacologic Management of Pain During Common Needle Puncture Procedures in Infants: Current Research Evidence and Practical Considerations: An Update.

Infants undergo painful procedures involving skin puncture as part of routine medical care. Pain from needle puncture procedures is suboptimally managed. Numerous nonpharmacologic interventions are available that may be used for these painful procedures, including swaddling/containment, pacifier/non-nutritive sucking, rocking/holding, breastfeeding and breastmilk, skin-to-skin care, sweet tasting solutions, music therapy, sensorial saturation, and parental presence. Adoption these interventions into routine clinical practice is feasible and should be a standard of care in quality health care for infants. This review summarizes the epidemiology of pain from common needle puncture procedures in infants, the effectiveness of nonpharmacologic interventions, implementation considerations, and unanswered questions.

Safety of fentanyl for peripherally inserted central catheter in non-intubated infants in the neonatal intensive care unit.

OBJECTIVE: To evaluate the safety of fentanyl in non-intubated infants undergoing peripherally inserted central catheter (PICC) placement. METHODS: A retrospective chart review of PICC placements over a 3 years' period. We compared the 12h periods before and after fentanyl for clinically significant cardiorespiratory events (spells). RESULTS: Of the 998 neonates screened, 258 were eligible. The mean standard deviation gestational age was 34.1 (4.3) weeks and the median (inter-quartile range) postnatal age was 4 (7, 11) days. The mean (standard deviation) fentanyl dose was 0.6 (0.2) µg/kg. Respiratory depression occurred only in two infants (prevalence rate = 0.78%, 95% CI (0, 1.85)). No cases of hypotension or chest wall rigidity occurred. There was no evidence of an increase in the number of infants with spells or in the number of spells per infant (p = 0.34 and p = 0.06, respectively). CONCLUSION: Fentanyl appears to be associated with only a small risk of respiratory depression in non-intubated infants.

Characterisation of proteins in excretory/secretory products collected from salmon lice, Lepeophtheirus salmonis.

BACKGROUND: The salmon louse, Lepeophtheirus salmonis, is an ectoparasitic copepod which feeds on the mucus, skin and blood of salmonid fish species. The parasite can persist on the surface of the fish without any effective control being exerted by the host immune system. Other ectoparasitic invertebrates produce compounds in their saliva, excretions and/or secretions which modulate the host immune responses allowing them to remain on or in the host during development. Similarly, compounds are produced in secretions of L. salmonis which are thought to be responsible for immunomodulation of the host responses as well as other aspects of crucial host-parasite interactions. METHODS: In this study we have identified and characterised the proteins in the excretory/secretory (E/S) products of L. salmonis using LC-ESI-MS/MS. RESULTS: In total 187 individual proteins were identified in the E/S collected from adult lice and pre-adult sea lice. Fifty-three proteins, including 13 serine-type endopeptidases, 1 peroxidase and 5 vitellogenin-like proteins were common to both adult and pre-adult E/S products. One hundred and seven proteins were identified in the adult E/S but not in the pre-adult E/S and these included serine and cysteine-type endopeptidases, vitellogenins, sphingomyelinase and calreticulin. A total of 27 proteins were identified in pre-adult E/S products but not in adult E/S. CONCLUSIONS: The assigned functions of these E/S products and the potential roles they play in host-parasite interaction is discussed.

The minimally effective dose of sucrose for procedural pain relief in neonates: a randomized controlled trial.

BACKGROUND: Orally administered sucrose is effective and safe in reducing pain intensity during single, tissue-damaging procedures in neonates, and is commonly recommended in neonatal pain guidelines. However, there is wide variability in sucrose doses examined in research, and more than a 20-fold variation across neonatal care settings. The aim of this study was to determine the minimally effective dose of 24% sucrose for reducing pain in hospitalized neonates undergoing a single skin-breaking heel lance procedure. METHODS: A total of 245 neonates from 4 Canadian tertiary neonatal intensive care units (NICUs), born between 24 and 42 weeks gestational age (GA), were prospectively randomized to receive one of three doses of 24% sucrose, plus non-nutritive sucking/pacifier, 2 min before a routine heel lance: 0.1 ml (Group 1; n = 81), 0.5 ml (Group 2; n = 81), or 1.0 ml (Group 3; n = 83). The primary outcome was pain intensity measured at 30 and 60 s following the heel lance, using the Premature Infant Pain Profile-Revised (PIPP-R). The secondary outcome was the incidence of adverse events. Analysis of covariance models, adjusting for GA and study site examined between group differences in pain intensity across intervention groups. RESULTS: There was no difference in mean pain intensity PIPP-R scores between treatment groups at 30 s (P = .97) and 60 s (P = .93); however, pain was not fully eliminated during the heel lance procedure. There were 5 reported adverse events among 5/245 (2.0%) neonates, with no significant differences in the proportion of events by sucrose dose (P = .62). All events resolved spontaneously without medical intervention. CONCLUSIONS: The minimally effective dose of 24% sucrose required to treat pain associated with a single heel lance in neonates was 0.1 ml. Further evaluation regarding the sustained effectiveness of this dose in reducing pain intensity in neonates for repeated painful procedures is warranted. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02134873. Date: May 5, 2014 (retrospectively registered).

Safety of Rectal Administration of Acetaminophen in Neonates.

BACKGROUND: On the basis of pharmacokinetic modelling, high-dose acetaminophen by rectal administration has been recommended for neonates needing antipyretic or analgesic therapy, but the safety and efficacy of this approach have not been established in vivo. OBJECTIVES: The primary objective was to assess the safety of rectal acetaminophen administration for neonates, as indicated by changes in the results of hepatic and renal function tests. The secondary objective was to assess the efficacy of rectal acetaminophen administration in terms of the Premature Infant Pain Profile-Revised (PIPP-R) score. METHODS: This single-centre retrospective chart analysis was conducted in the neonatal intensive care unit at a quaternary care children's hospital. Neonates who received all prescribed doses of acetaminophen by continu - ous rectal administration for 24 h or more, from January 1, 2011, to December 31, 2012, were included. For the primary objective, hepatotoxicity was assessed in terms of changes in liver enzyme levels, and nephrotoxicity was assessed in terms of changes from baseline serum creatinine values. RESULTS: Twenty-five patients, who received a total of 27 courses of acetaminophen by rectal administration, met the inclusion criteria. Median gestational age at initiation of acetaminophen was 37.0 weeks (interquartile range 35.0-39.8 weeks). Values of alanine aminotransferase remained within normal limits during acetaminophen therapy for all but 3 patients, for whom the changes were attributable to confounding factors. Renal function remained unchanged. The secondary outcome of efficacy (based on PIPP-R score) could not be evaluated because of concurrent use of opioids for most patients. CONCLUSIONS: Continuous rectal administration of acetaminophen over a short period (< 48 h) appeared to be well tolerated. The conclusions that can be drawn from these results are limited because of small sample size, the prescribing of doses lower than those recommended by the hospital's formulary, and limited blood sampling. Further studies are required.

CONTEXTE: Selon une modélisation pharmacocinétique, des doses élevées d'acétaminophène administré par voie rectale ont été recommandées comme traitement antipyrétique ou analgésique chez le nouveau-né, mais l'innocuité et l'efficacité de cette modalité d'administration n'ont pas été établies in vivo. OBJECTIFS: L'objectif principal était d'évaluer l'innocuité de l'acétaminophène administré par voie rectale chez le nouveau-né en observant les changements dans les résultats des bilans hépatique et rénal. L'objectif secondaire était d'évaluer l'efficacité de l'acétaminophène administré par voie rectale à l'aide du score obtenu dans le Premature Infant Pain Profile-Revised (PIPP-R). MÉTHODES: La présente étude rétrospective menée dans un seul centre comportait une analyse des dossiers médicaux de patients admis à l'unité de soins intensifs néonatals d'un établissement de soins quaternaires pour enfants. Les nouveau-nés ayant reçu toutes les doses prescrites d'acétaminophène par administration rectale ininterrompue pendant 24 heures ou plus, entre le 1er janvier 2011 et le 31 décembre 2012, étaient admissibles à l'étude. Pour l'objectif principal, l'hépatotoxicité a été évaluée en fonction des variations observées dans les taux d'enzymes hépatiques et la néphrotoxicité a été évaluée en fonction des changements observés dans la créatininémie par rapport aux valeurs de départ. RÉSULTATS: Vingt-cinq patients qui ont reçu un total de 27 traitements par acétaminophène administré par voie rectale répondaient aux critères d'inclusion. L'âge gestationnel médian lors de l'amorce du traitement par acétaminophène était de 37,0 semaines (écart interquartile de 35,0 semaines à 39,8 semaines). Les valeurs d'alanine-aminotransférase demeuraient à l'intérieur des limites normales pendant le traitement par acétaminophène pour tous les patients à l'exception de trois pour lesquels les changements étaient attribués à des facteurs de confusion. La fonction rénale demeurait inchangée. Le critère d'évaluation secondaire quant à l'efficacité (s'appuyant sur le score obtenu dans le PIPP-R) n'a pu être évalué en raison de la prise concomitante d'opioïdes chez la plupart des patients. CONCLUSIONS: L'administration rectale ininterrompue d'acétaminophène pendant une courte période (moins de 48 heures) semblait être bien tolérée. Cependant, les conclusions qui peuvent être tirées de ces résultats sont limitées en raison de la petite taille de l'échantillon, de la prescription de doses plus faibles que celles recommandées dans la liste des médicaments de l'hôpital et de l'insuffisance des échantillons sanguins. De plus amples études sont nécessaires.

A cohort study of intranasal fentanyl for procedural pain management in neonates.

OBJECTIVES: The objective of this cohort study was to document experience with intranasal (IN) fentanyl analgesia for procedural pain management in neonates in a surgical neonatal intensive care unit. A consecutive sample of 23 neonates without intravenous access treated with IN fentanyl was included. METHODS: Data were extracted from medical charts, including infant characteristics, indication for IN fentanyl, dose, physiologic parameters (heart rate, respiratory rate, oxygen saturation, blood pressure) and pain scores. Physiologic parameters were recorded for 6 hours before and after IN fentanyl. Pain scores were recorded during and after the procedure using the Premature Infant Pain Profile (PIPP). RESULTS: The mean (SD) postmenstrual age of included infants was 31.8 weeks (4.1), and 52% were receiving some form of ventilator support. The mean dose of IN fentanyl was 1.3 mcg/kg (0.4) and most common indication was analgesia for peripheral insertion of central catheter. There were six cases of cardiorespiratory depression as defined, however, clinical factors could account for all of them. The mean PIPP score during and after the procedure was 4.3 (1.8) and 3.6 (1.5), respectively (scores <6 indicate no pain). CONCLUSIONS: This small study provides some preliminary evidence of the benefits and risks of IN fentanyl in this population.

A randomized trial of rotavirus vaccine versus sucrose solution for vaccine injection pain.

OBJECTIVE: Sucrose solutions are analgesic in infants. Oral rotavirus vaccine contains sucrose, however, it is not known if it possesses analgesic properties. The objective was to compare the analgesic effectiveness of rotavirus vaccine to sucrose solution when administered prior to injectable vaccines. METHODS: Infants 2-4 months of age receiving oral rotavirus vaccine and two separate injectable vaccines on the same day were randomized to rotavirus vaccine (Rotarix) first followed by the injectable vaccines and sucrose (Tootsweet) afterwards, or vice versa. Pain was assessed by blinded raters using the Numerical Rating Scale (NRS, range 0-10) (parents, clinicians), or Modified Behavioural Pain Scale (MBPS, range 0-10) and cry duration (observers). Data were analyzed using t-tests or χ(2)-tests; Bonferroni correction was applied to correct for multiple comparisons, as appropriate. RESULTS: Altogether, 120 infants participated: 60 were randomized to rotavirus vaccine first. Groups did not differ in demographics, including; age (p=0.448) and sex (p=0.464). The mean pain score (standard deviation) for both vaccine injections did not differ between infants given rotavirus vaccine first versus sucrose solution first: observer MBPS, parent NRS and clinician NRS scores were 7.4 (1.6) vs. 7.7 (1.6), 4.9 (2.1) vs. 5.8 (2.1), and 4.2 (2.1) vs. 4.6 (2.2), respectively. Similarly, there was no difference between groups in cry duration. CONCLUSION: Rotavirus vaccine did not differ from sucrose solution in reducing injection-induced pain. Based on the findings, it is recommended that rotavirus vaccine be administered prior to injectable vaccines in infants aged 2 and 4 months.

Ectoparasites of medical and veterinary importance: drug resistance and the need for alternative control methods.

OBJECTIVES: Despite multiple attempts at eradication, many ectoparasites of humans and domestic livestock remain a persistent problem in the modern world. For many years, a range of pesticide drugs including organophosphates, organochlorides and synthetic pyrethroids provided effective control of these parasites; but intensive use of these drugs has led to the evolution of resistance in many target species. This paper aims to review the effectiveness of current control methods and discuss potential alternatives for the long term sustainable control of ectoparasites. KEY FINDINGS: Important medical ectoparasites such as scabies mites, head lice and bed bugs present a significant public health problem, and so adequate control methods are essential. Ectoparasites of domestic livestock and farmed fish (for example sheep scab mites, poultry mites and sea lice) are also of concern given the increasing strain on the world's food supply. These parasites have become resistant to several classes of pesticide, making control very difficult. Recently, an increasing amount of research has focussed on alternative control methods such as insect growth regulators, biological control using essential oils or fungi, as well as vaccine development against some ectoparasites of medical and veterinary importance. SUMMARY: Drug resistance is prevalent in all of the ectoparasites discussed in this review. A wide variety of alternative control methods have been identified, however further research is necessary in order for these to be used to successfully control ectoparasitic diseases in the future.

Nonpharmacological management of pain during common needle puncture procedures in infants: current research evidence and practical considerations.

All infants undergo painful procedures involving skin puncture as part of routine medical care. Pain from needle puncture procedures is suboptimally managed. Numerous nonpharmacologic interventions are available for these painful procedures, including swaddling, holding, skin-to-skin care, pacifier, sweet-tasting solutions, and breast-feeding. Adoption of nonpharmacologic pain-relieving interventions into routine clinical practice is feasible and should be a standard of care in the delivery of quality health care for infants. This review summarizes current knowledge about the epidemiology of pain from common needle puncture procedures in infants, the effectiveness of nonpharmacologic interventions, implementation considerations, and unanswered questions for future research.

Arrhythmia associated with tetracaine in an extremely low birth weight premature infant.

Infants in NICUs undergo a variety of painful procedures. The management of pain has become an integral part of newborn infant care with the use of both systemic and topical agents to provide analgesia and anesthesia for procedural pain. Tetracaine and prilocaine-lidocaine are the 2 topical anesthetics most frequently used. Tetracaine belongs to an ester group of local anesthetics available as a topical 4% gel (Ametop, Smith and Nephew, Canada). The major side effects reported when using topical anesthetics are cutaneous reactions. There are no definite reports of systemic toxicity in the published literature. We present a recent case of an extremely low birth weight premature infant who developed a clinically significant arrhythmia after topical tetracaine was applied before the insertion of a peripherally inserted central catheter. The infant had no other identifiable cause for the resulting bradycardia that occurred only after Ametop was applied. The cardiac symptoms resolved with treatment. This case highlights a significant potential adverse event when using topical tetracaine.

Development of a cDNA microarray for the measurement of gene expression in the sheep scab mite Psoroptes ovis.

BACKGROUND: Sheep scab is caused by the ectoparasitic mite Psoroptes ovis which initiates a profound cutaneous inflammatory response, leading to the development of the skin lesions which are characteristic of the disease. Existing control strategies rely upon injectable endectocides and acaricidal dips but concerns over residues, eco-toxicity and the development of acaricide resistance limit the sustainability of this approach. In order to identify alternative means of disease control, a deeper understanding of both the parasite and its interaction with the host are required. METHODS: Herein we describe the development and utilisation of an annotated P. ovis cDNA microarray containing 3,456 elements for the measurement of gene expression in this economically important ectoparasite. The array consists of 981 P. ovis EST sequences printed in triplicate along with 513 control elements. Array performance was validated through the analysis of gene expression differences between fed and starved P. ovis mites. RESULTS: Sequences represented on the array include homologues of major house dust mite allergens and tick salivary proteins, along with factors potentially involved in mite reproduction and xenobiotic metabolism. In order to validate the performance of this unique resource under biological conditions we used the array to analyse gene expression differences between fed and starved P. ovis mites. These analyses identified a number of house dust mite allergen homologues up-regulated in fed mites and P. ovis transcripts involved in stress responses, autophagy and chemosensory perception up-regulated in starved mites. CONCLUSION: The P. ovis cDNA microarray described here has been shown to be both robust and reproducible and will enable future studies to analyse gene expression in this important ectoparasite.