Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is associated with an increased incidence and aggressiveness of skin cancers, particularly cutaneous squamous cell carcinoma (cSCC), but little is known about cSCC incidence in Australasian CLL patients. AIM: In this retrospective study, we analysed the incidence of cSCC in patients seen at a tertiary hospital in New Zealand (NZ). METHODS: We retrospectively assessed the clinical history and histology data of CLL patients (n = 371) who presented to the Haematology Department, Christchurch Hospital, NZ during the period 1996-2015. Baseline characteristics, incidence of second cancers, treatment details and overall survival were analysed. RESULTS: During follow-up (median = 11.8 years), 221 second cancers were recorded in 88 patients. Of these cancers, 185 were cSCC, removed from 61 patients. In 56% of these patients, >1 cSCC was removed, and the majority of cSCC occurred following the treatment for CLL. The cumulative incidence of a first cSCC was 11% at 5 years, whereas the cumulative incidence of a subsequent cSCC was 88% at 5 years. The incidence of cSCC in male patients was threefold higher than that reported for the general NZ population. CONCLUSION: NZ CLL patients have a high incidence of cSCC relative to the levels observed in the general population, which are themselves among the highest in the world. The careful monitoring of CLL patients is warranted, particularly those who have a progressive disease or have had a first cSCC removed.

Early retinal blood vessel growth in normal and growth restricted rat pups raised in oxygen and room air.

BACKGROUND/AIMS: Premature infants are born with incompletely vascularised retinas and are at a risk of developing retinopathy of prematurity (ROP). Rate of prenatal and postnatal body growth is important in the pathogenesis of ROP. The aim of this study was to develop a physiology-based rat model in order to study the effect of growth restriction and oxygen on early retinal vascular development. METHODS: Rat mothers were fed either a normal (18% casein) or low (9% casein) protein diet (to cause pup growth restriction) from the last week of gestation. After birth, mother and pups were placed in either room air or a specialised oxygen chamber that delivered a rapidly fluctuating hyperoxic oxygen profile. The oxygen profile was based on that from a premature infant who developed severe ROP. On day 14, retinas were dissected, flat-mounted and stained using biotinylated lectin. Images were captured by confocal microscopy. The avascular areas of the retinas were measured and compared. RESULTS: Growth restricted rat pups had significantly larger retinal avascular areas than 'normally grown' rat pups (Mann-Whitney U test, p<0.001). Growth restricted rat pups raised in fluctuating oxygen had significantly larger retinal avascular areas than growth restricted rat pups raised in room air (Mann-Whitney U test, p=0.001). CONCLUSIONS: The authors have developed a novel model for ROP that involves inducing both intrauterine and postnatal growth restriction and also exposes neonatal rat pups to fluctuating oxygen. This physiology-based model can be used to study the effects of growth, nutrition and oxygen on early retinal vascular development.

The epidemiology of oro-nasal haemorrhage and suffocation in infants admitted to hospital in Scotland over 10 years.

OBJECTIVE: To estimate the incidence of oro-nasal haemorrhage (ONH) and suffocation in infancy and to investigate their aetiology and overlap. Setting A 10-year retrospective hospital based study from Scotland, UK. METHODS: The hospital notes of all infants presenting with ONH or suffocation identified through the Information Services Division of the Scottish Health Service were reviewed by three paediatric consultants, two with child protection expertise. The hospital-based incidences of haemorrhages from different sites were calculated and the causes ascertained. When trauma was involved, a decision was made whether it was likely to have been accidental. RESULTS: 7 cases of suffocation and 88 of ONH were recorded at hospital discharge over 10 years. This gives an incidence of ONH of 1.62 (1.30 to 1.99)/10,000 live births (95% CI) which consists of haemorrhage arising from nose or mouth (N/M), n=65 (1.19/10,000 (0.92 to 1.52)); haematemesis, n=11 (0.20/10,000 (0.10 to 0.36)); haemoptysis, n=3 (0.06/10,000 (0.1 to 0.16)) and pulmonary haemorrhage, n=9 (0.17/10,000 (0.08 to 0.31)). No suffocation cases were recorded as having a coincident ONH, but five ONH cases were probably caused by airway obstruction. 40 of 65 cases of N/M were associated with trauma, which in 15 cases were thought to be probable abuse; four were associated with coagulation abnormalities. 2/3 haemoptysis cases, 2/11 haematemesis cases and 8/65 N/M cases were associated with a coincident respiratory tract infection, though in 4/8 of these cases, there was an associated apparent life-threatening event. CONCLUSIONS: Haemorrhage from the N/M is rare in infancy. Trauma is commonly involved and child protection concerns often poorly explored. Pulmonary haemorrhage and several cases of ONH were associated with probable airway obstruction. Information, in cases of ONH, is in general recorded badly, and an investigation and management plan are suggested.

The use of electronic reporting to aid surveillance of ADRs in children: a proof of concept study.

OBJECTIVE: To investigate: (1) the feasibility of establishing active paediatric surveillance for adverse drug reactions (ADRs), (2) whether electronic reporting is effective and (3) whether such a system could complement the Medicines and Healthcare products Regulatory Agency (MHRA) yellow card system. DESIGN: Between January 2006 and February 2007 ADRs in children under 16 were reported each month by consultant paediatricians and paediatric pharmacists in Scotland. For 8 months respondents received a postal card, after which half were selected to report electronically via an email card for a further 6 months and half continued with the postal card. Reports of paediatric ADRs severe enough to warrant hospital admission or to delay discharge of hospitalised patients or resulting from an outpatient prescription were followed up. A postal questionnaire evaluated the system at the end of the study. RESULTS: Following a 2-month lead-in period, 83% of the cards were returned over the year, 84% by paediatricians and 82% by pharmacists. With electronic reporting the response rate was 80%. Eighty-seven confirmed reports of a drug being associated with one or more adverse reactions were reported in 67 children. Only eight children were also identified through the MHRA yellow card system. Respondents indicated continuing willingness to contribute to an active (preferably electronic) reporting system. CONCLUSIONS: Active paediatric ADR surveillance is feasible; electronic reporting is effective and data collected are different to, but could complement, those collected by the MHRA yellow card.

Pain in neonates during screening for retinopathy of prematurity using binocular indirect ophthalmoscopy and wide-field digital retinal imaging: a randomised comparison.

OBJECTIVE: To compare the pain experienced by premature infants undergoing wide-field digital retinal imaging (WFDRI) and binocular indirect ophthalmoscopy (BIO) for retinopathy of prematurity (ROP) screening. METHODS: Infants were recruited at Edinburgh Royal Infirmary Neonatal Unit, Edinburgh, UK. Eyes were examined by WFDRI and BIO with eyelid speculum by two experienced paediatric ophthalmologists in random order. A pain score (Premature Infant Pain Profile (PIPP)) for WFDRI and BIO was generated. RESULTS: A total of 76 infants were recruited. The (mean, SD) PIPP score for WFDRI was 15.0, 2.1 and for BIO was 15.2, 2.4 (paired t test p=0.47). The authors observed that infants started crying with corresponding physiological changes as soon as the eyelid speculum was inserted and crying stopped on speculum removal. CONCLUSION: WFDRI and BIO with eyelid speculum are similarly painful for infants. The authors speculate that the eyelid speculum rather than the examination method may contribute most to the pain experienced.

An audit of transfers for neonatal surgical care in England in 2007.

OBJECTIVE: To audit the access to specialist services for infants requiring transfer for surgical care in the neonatal networks in England in 2007. METHODS: Data on neonates transferred for surgical care from January to December 2007 were obtained from the National Neonatal Audit Programme database. Information on origin and destination of transfer was used to assess what proportion of infants required transfer to another network or, in the six network centres without a surgical service, to a more distant surgical centre than appropriate. RESULTS: Information was available from 18 of the 24 neonatal networks and identified 484 infants transferred for surgery for whom complete data were available. Ninety-one infants (18.8%) were transferred out of network or to a more distant centre than appropriate. This compares with 3.6% for all network patients and far exceeds the maximum figure of 5% recommended by the National Audit Office. Only one network was able to use a single surgical centre for transfers, and the median number of surgical units accessed in the year was 3 (range 1-8). CONCLUSIONS: Neonates requiring surgical care in England often need transfer beyond the local network. The reasons for this need further investigation by a prospective audit of access to neonatal surgical care.

Wide-field digital retinal imaging versus binocular indirect ophthalmoscopy for retinopathy of prematurity screening: a two-observer prospective, randomised comparison.

AIM: To compare the diagnostic accuracy of wide-field digital retinal imaging (WFDRI) with the current "gold standard" of binocular indirect ophthalmoscopy (BIO) for retinopathy of prematurity (ROP) screening examinations. METHODS: A consecutive series of premature infants undergoing ROP screening at Edinburgh Royal Infirmary were eligible for recruitment into this prospective, randomised, comparative study. Infants were screened using both WFDRI (Retcam II with neonatal lens) and BIO by two paediatric ophthalmologists who were randomised to the examination technique. Both examiners documented their clinical findings and management plans in a masked fashion. WFDRI eye findings were compared with those of BIO. RESULTS: A total of 81 infants were recruited, and information from 245 eye examinations was analysed. The sensitivity of WFDRI in detecting any stage of ROP, stage 3 ROP and "plus" disease was 60%, 57% and 80%, respectively, and specificity 91%, 98% and 98%, respectively. The proportional agreement between WFDRI and BIO was 0.96 for detecting stage 3 disease and 0.97 for detecting "plus" disease. There was very good agreement on management decisions (kappa 0.85). CONCLUSION: When used in a routine ROP screening setting, a randomised comparison of WFDRI and BIO, WFDRI showed relatively poor sensitivity in detecting mild forms of ROP in the retinal periphery. This resulted in difficulty in making decisions to discharge infants from the screening programme. Sensitivity was better for more severe forms of ROP, but at present WFDRI should be regarded as an adjunct to, rather than a replacement for, BIO in routine ROP screening.

Retinopathy of prematurity in small-for-gestational age infants compared with those of appropriate size for gestational age.

AIM: To compare the incidence of retinopathy of prematurity (ROP) in small-for-gestational age (SGA) infants compared with appropriate-for-gestational age (AGA) infants undergoing eye screening in the Lothian region of south east Scotland 1990-2004. METHODS: All infants in Lothian born with birth weight <1500 g and/or gestational age <32 weeks underwent eye screening by two experienced paediatric ophthalmologists. The presence of any stage of ROP (1-5), severe (stage 3 or greater) ROP and treated ROP was compared between the SGA and AGA infants using chi(2) or Fisher exact tests. SGA was defined as birth weight below the 10th centile for gestational age. RESULTS: A total of 1413 babies with birth weights <1500 g and/or gestational age <32 weeks underwent eye screening; 329 (23%) were SGA. SGA infants born at gestational ages 26-31 weeks were more likely to develop any stage of ROP (p<0.01) than their AGA peers. SGA infants were also more likely to develop severe ROP (gestational age 26-27 weeks, p<0.01; 28-29 weeks, p = 0.01; 30-31 weeks, p = 0.01). CONCLUSIONS: SGA infants who underwent eye screening in the Lothian region of south east Scotland from 1990 to 2004 were significantly more likely to develop ROP and more severe disease than AGA infants.

Neonatal blood pressure waves are associated with surges of systemic noradrenaline.

Neonatal blood pressure (BP) waves have been linked to neonatal illness. We investigated plasma levels of vasoactive hormones when BP waves were observed. Peak and trough noradrenaline levels correlated with mean BP (p = 0.028). There was no relationship to adrenaline, dopamine or endothelin levels.

Incidence of retinopathy of prematurity in Lothian, Scotland, from 1990 to 2004.

BACKGROUND: To report the trends in incidence of retinopathy of prematurity (ROP) within Lothian, a geographically defined region in southeast Scotland over a 15-year period from 1990 to 2004. METHODS: This was a prospective observational study of all infants born with gestational age <32 weeks and/or birth weight <1500 g who were born to mothers resident in Lothian between 1 January 1990 and 31 December 2004. Eligible infants underwent eye screening by two experienced paediatric ophthalmologists (BF and EW). Lothian population data were obtained from the Scottish Health Service. The trends in survival rates, incidence and treatment of ROP were analysed from 1990 to 1994, 1995 to 1999 and 2000 to 2004. RESULTS: Lothian population data showed a steady decline in the number of live births from 1990 to 2004. The proportion of babies born with birth weight <1500 g and/or gestational age <32 weeks remained constant (p = 0.271 using chi(2) test), although the proportion of these babies surviving to 42 weeks corrected gestation increased from 1990 to 2004 (p<0.001 using chi(2) test for trend). There was a statistically significant linear trend towards a reduction in the number of babies undergoing treatment for ROP throughout the study period (p<0.01 using chi(2) test for trend). A reduction in the incidence of any degree of ROP and severe (stage 3 or greater) ROP was also observed although this did not reach statistical significance. CONCLUSIONS: There was a significant increase in survival of infants with birth weight <1500 g and/or gestational age <32 weeks together with a significant reduction in the number of infants treated for ROP in the Lothian region of southeast Scotland from 1990 to 2004.

Morphine analgesia and gastrointestinal morbidity in preterm infants: secondary results from the NEOPAIN trial.

OBJECTIVE: To investigate the influence of morphine therapy and other factors on the attainment of full enteral feeds and on acquired gastrointestinal pathology in preterm infants. DESIGN: Secondary data analysis from a randomised, placebo controlled trial. SETTING: 16 neonatal intensive care units in USA, Sweden, France and UK. PATIENTS: 898 infants (treatment group 449, control 449). Gestation (median (range)): 27 (23-32) weeks; birth weight (median (range)): 985 (420-2440) g. INTERVENTIONS: Morphine (M) or placebo (Pl) given pre-emptively by intravenous loading dose (100 microg/kg of morphine) and infusion (10-30 microg/kg/h depending on gestation) while infants were ventilated, for up to 14 days. "Open-label" morphine (A) could be given if clinically indicated. MAIN OUTCOME MEASURES: Age at full enteral feeds and major acquired gastrointestinal pathology. RESULTS: The group randomised to morphine was later in attaining full feeds (median days (quartiles): M 20 (13-29), Pl 17 (12-26); p = 0.003), and in starting feeds (median days (quartiles): M 5 (3-8), Pl 4 (2-7)). In a linear regression model, age at full feeds was independently associated with birth weight, a score of neonatal morbidities, neonatal dexamethasone use and cumulative morphine dose. There was no relationship between morphine use and acquired gastrointestinal pathology (M 9/449, Pl 8/449; chi2 p = 0.81). CONCLUSIONS: Morphine delays the attainment of full enteral feeds, partly by delaying the start of feeding, but does not discernibly increase gastrointestinal complications. The attainment of full feeds is influenced by morphine dose, but other factors seem to be important, including birth weight and neonatal morbidity.

Effect of suckling on the peripheral sensitivity of full-term newborn infants.

BACKGROUND: Sucking may reduce the manifestations of pain in newborn infants. OBJECTIVE: To examine the effect of suckling on the threshold for peripheral somatosensory responses. SUBJECTS AND METHODS: Graded Von Frey filaments were applied to the heel to initiate peripheral somatosensory responses (withdrawal reflex and gross body movements) in term infants. RESULTS: Dummy sucking increases the somatosensory threshold, but breast feeding had a more marked effect, increasing the threshold of the flexion withdrawal reflex (p

The Scottish Perinatal Neuropathology Study--clinicopathological correlation in stillbirths.

OBJECTIVE: To examine the neuropathology of fetuses dying before birth, to determine the timing of any brain damage seen and to ascertain clinical associations of pre-existing brain damage. DESIGN: Population-based observational study. SETTING: All 22 delivery units within Scotland, 1995-1998. SAMPLE: All stillborn fetuses > or =24 weeks of gestation excluding those with chromosomal abnormality or central nervous system/cardiothoracic malformation. METHODS: Clinical detail was collected on all stillborn fetuses. Requests for postmortem included separate request for detailed neuropathological examination. Stillborn fetuses were classified as full term antepartum (normal growth/growth restricted), preterm antepartum (normal growth/growth restricted), intrapartum (full term/preterm), multiple births and stillborn fetuses following abruptions. Clinicopathological correlation attempted to define the timing of brain insult. Placentas were examined for each case where available. MAIN OUTCOME MEASURES: Presence of established and/or recent brain damage. RESULTS Clinical details were available for 471 stillborn fetuses, and detailed neuropathology was possible in 191 cases. Of these 191, 13 were multiple births, 9 died following abruption, 12 were intrapartum deaths and 157 were antepartum stillborn fetuses (99 preterm and 58 full term). Recent or established brain damage was seen in 66% of the entire cohort. Thirty-five percent of all cases showed well-established hypoxic damage predating the last evidence of fetal life, and this was more common in preterm fetuses (P = 0.015), those fetuses with evidence of recent damage (P < 0.001), in pregnancies complicated by pregnancy-induced hypertension (P = 0.044) and those in whom the placenta was <10th centile (P = 0.002). CONCLUSIONS: Brain damage is commonly seen in stillborn infants, and in around one-third of cases, damage predates the period immediately before death. Factors suggesting suboptimal placental function are associated with such damage. Early identification of placental impairment may lead to improved pregnancy outcome.

Sucrose and non-nutritive sucking for the relief of pain in screening for retinopathy of prematurity: a randomised controlled trial.

BACKGROUND: Screening is necessary for infants at risk of retinopathy of prematurity. Despite local anaesthetic drops, infants find eye examinations distressing, displaying behavioural and physiological changes indicating acute pain. Oral sucrose and non-nutritive sucking reduce pain responses associated with invasive procedures. OBJECTIVE: To evaluate the use of oral sucrose and/or pacifier for reducing pain responses during eye examinations. METHODS: Forty infants <32 weeks gestation or <1500 g birth weight, in two neonatal units, were randomised to one of four interventions administered two minutes before their first screening examination: 1 ml sterile water as placebo (group 1, n = 10), 1 ml 33% sucrose solution (group 2, n = 10), 1 ml sterile water with pacifier (group 3, n = 9), or 1 ml 33% sucrose solution with pacifier (group 4, n = 11). Examinations were videotaped. Two observers, blind to the intervention, assessed recordings. Pain responses were scored using the premature infant pain profile (PIPP). RESULTS: The groups were similar in gestation, birth weight, and age at examination. Mean PIPP scores were 15.3, 14.3, 12.3, and 12.1 for groups 1, 2, 3, and 4 respectively. Analysis of variance showed a significant difference in PIPP score between groups (p = 0.023). Infants randomised to pacifiers scored lower than those without pacifiers (p = 0.003). There was no difference between groups receiving sucrose and those receiving water (p = 0.321). CONCLUSIONS: Non-nutritive sucking reduced distress responses in infants undergoing screening for retinopathy of prematurity. The difference in response was large enough to be detected by a validated assessment tool. No synergistic effect of sucrose and pacifier was apparent in this group.

The distribution of apolipoprotein E alleles in Scottish perinatal deaths.

BACKGROUND: The apolipoprotein E (ApoE) polymorphism has been well studied in the adult human population, in part because the e4 allele is a known risk factor for Alzheimer's disease. Little is known of the distribution of ApoE alleles in newborns, and their association with perinatal brain damage has not been investigated. METHODS: ApoE genotyping was undertaken in a Scottish cohort of perinatal deaths (n = 261), some of whom had prenatal brain damage. The distribution of ApoE alleles in perinatal deaths was compared with that in healthy liveborn infants and in adults in Scotland. RESULTS: ApoE e2 was over-represented in 251 perinatal deaths (13% v 8% in healthy newborns, odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.13 to 2.36 and 13% v 8% in adults, OR = 1.67, 95% CI 1.16 to 2.41), both in liveborn and stillborn perinatal deaths. In contrast, the prevalence of ApoE e4 was raised in healthy liveborn infants (19%) compared with stillbirths (13%, OR = 1.59, 95% CI 1.11 to 2.26) and with adults (15%, OR = 1.35, 95% CI 1.04 to 1.76). However, no correlation was found between ApoE genotype and the presence or absence of perinatal brain damage. CONCLUSIONS: This study shows a shift in ApoE allelic distribution in early life compared with adults. The raised prevalence of ApoE e2 associated with perinatal death suggests that this allele is detrimental to pregnancy outcome, whereas ApoE e4 may be less so. However, ApoE genotype did not appear to influence the vulnerability for perinatal hypoxic/ischaemic brain damage, in agreement with findings in adult brains and in animal models.

Low oxygen exposure does not cause pulmonary injury in the newborn rat.

BACKGROUND: Two recent studies have suggested that low levels of supplemental inspired oxygen may cause lung injury in preterm infants. AIMS: To assess lung injury of newborn rats exposed to 14 days of low-level variation of oxygen. STUDY DESIGN: Four groups were compared with 12 animals per group and 4 lung sections per animal. These were, a control group raised in room air and three groups raised in levels of inspired oxygen fluctuating around the following mean values: group Lo (mean FiO(2) 0.179), group N (mean FiO(2) 0.213), and group Hi (mean FiO(2) 0.247). The degree of oxygen variability was identical for each group. Lungs were inflated at 20 cm H(2)O, fixed and stained with H and E and Millers Elastin. SUBJECTS: Sprague Dawley albino newborn rats. OUTCOME MEASURES: Random alveolar areas were studied and analysed using imaging software to assess total amount of tissue and elastin, number of secondary septa, and mean linear intercept. RESULTS: There were no significant differences between the three experimental oxygen groups and the control group in terms of lung/body weight ratio and the measured markers of lung development. CONCLUSION: We conclude that low-level oxygen supplementation during early lung development does not affect alveolar development in the newborn rat.

Distribution of apolipoprotein E alleles in a Scottish healthy newborn population.

The different alleles of the human apolipoprotein E polymorphism, ApoE epsilon2, epsilon3, epsilon4, have important implications for systemic lipid metabolism, immunological function and for the brain in maintenance and in response to injury. Few studies have focussed on their role in early life. The ApoE alleles and genotypes were ascertained in the cord blood of 371 full-term and normal Scottish newborn infants using PCR methodology. The results were compared to previously published data for Scottish adults in late middle age. There was a marginally significant over-representation of epsilon4 and under-representation of epsilon3 alleles in healthy infants as compared with adults. Inspection of the individual genotypes confirms the over-representation of ApoE 4/4 and 2/4 with a reduction in ApoE 2/3 and 3/3 when compared with Scottish adults. Although these results may have occurred by chance, the ApoE epsilon4 allele may confer an increased risk of premature death.