A questionnaire survey on the usage of low protein staple foods by people with phenylketonuria in Scotland.

BACKGROUND: There is scarce evidence available with respect to an evaluation of the role of low protein staple foods (LPSF) in the management of phenylketonuria (PKU). The present study explored beliefs, acceptability and issues around the use of LPSF by people with PKU or their carers. METHODS: A semi-anonymous questionnaire was posted to 178 people with PKU in Scotland (104 children, aged 2-17 years, and 74 adults). Questions explored were: the type and amount of LPSF ordered; perceptions on use and usefulness of LPSF; acceptability of the LPSF sensory properties (i.e. taste, smell, texture, appearance); support for the supply and use of LPSF; and comments from primary healthcare professionals regarding dispensing and prescription. RESULTS: Eighty-two individuals responded (46% response rate): 97% perceived that LPSF were useful for PKU management; more than 85% reported that LPSF were important for phenylalanine control, satisfying appetite, and diet variety. The most common LPSF ordered were pasta/rice/cous cous, flour, biscuits and bread. Fifty percent of respondents ordered <51% of the recommended unit allowance of LPSF. The sensory properties of LPSF were well perceived. Forty-nine percent (n = 39) had received a comment from primary healthcare staff regarding the prescription or dispensing of LPSF; 59% (n = 23) received negative comments, the majority of which came within general practitioner surgeries. CONCLUSIONS: There is a positive attitude and perception on the use and usefulness of LPSF in the management of PKU. Issues with respect to the supply and provision of LPSF within primary health care may indicate poor communication between specialists and primary healthcare professionals or a lack of scientific evidence demonstrating their clinical effectiveness.

Evaluating the use of metabolite measurement in children receiving treatment with a thiopurine.

BACKGROUND: Clinical response to thiopurine medication is related to the concentration of its metabolites. Proxy measures are traditionally used to assess dose adequacy. We present our experience of using tioguanine (previously known/formerly referred to as thioguanine) metabolite measurements in paediatric patients and evaluate their effect on clinical practice. AIMS: To report our experience of using tioguanine metabolite measurements in paediatric patients and to evaluate their effects on clinical practice. METHODS: The 6-tioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) were measured in children prescribed thiopurine medication for at least 3 months. Data were collected on thiopurine methyl transferase (TPMT) genotype, drug dose, laboratory indices and management changes. Therapeutic 6-TGN levels were defined as 235-400 pmol/8 × 10(8) RBCs. Seventy individuals (30 males) with a median age of 15 years. Underlying diagnoses were 'IBD' (68/70) and two cases of eosinophilic colitis. Sixty-three were treated with azathioprine and seven with mercaptopurine. A total of 103 separate measurements were made. RESULTS: On initial measurement, 68% of patients had 6-TGN levels outside therapeutic levels despite standard thiopurine dosing. Initial 6-TGN levels were significantly higher in patients with TPMT mutations. Toxicity occurred in seven cases. The 6-TGN levels were significantly higher in those with signs of marrow toxicity. The 6-TGN level correlated with WBC, leukocyte count, mean corpuscular volume (MCV) and ΔMCV; however, the ability of each of these to predict therapeutic 6-TGN levels was poor. After initial measurement, management was changed in 25/70 cases (36%). CONCLUSIONS: 6-TGN levels were therapeutic in a minority of those patients who were tested. Proxy measures perform poorly in predicting therapeutic 6-TGN levels. Measuring thiopurine metabolites is useful for dosage adjustment in children, and for the detection of potential toxicity.

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.

BACKGROUND: It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). AIMS: To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. DESIGN AND SETTING: Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. INTERVENTION: Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. MAIN OUTCOME MEASURE: Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. RESULTS: Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. CONCLUSIONS: Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.

Therapeutic effect of a topical CCR2 antagonist on induced alveolar bone loss in mice.

BACKGROUND AND OBJECTIVE: Chemokines are known to regulate leukocyte trafficking, recruitment and infiltration in periodontal diseases. The study objective was to determine the effect of an experimental oral/topical chemokine (C-C motif) receptor 2 (CCR2)-antagonist treatment on alveolar bone loss in a mouse model of Porphyromonas gingivalis-induced periodontitis. MATERIAL AND METHODS: Balb/C mice (n = 41) were randomly assigned to four groups. Group 1 was infected by P. gingivalis applied orally/topically for 5 wk. Group 2 was also infected and then treated with vehicle (aqueous methylcellulose) for an additional 4 wk. Group 3 was infected and orally/topically treated with CCR2 antagonist (10 mg/kg). Group 4 served as a noninfected, nontreated control group. Mice received intraperitoneal injections of Alizarin (30 mg/kg) and calcein (20 mg/kg) three times from the last day of infection to determine mineral deposition, reflecting bone dynamics. Mandibles were analysed by morphometry and confocal fluorescence microscopy. RESULTS: Alveolar bone loss was compared among groups using Tukey's test, and bone formation was qualitatively observed. Infected mice showed significantly greater alveolar bone loss than noninfected control animals (group 1 vs. 4, p < 0.01). Vehicle-treated mice (group 2) showed the largest area of alveolar bone loss (p < 0.01), while mice treated with the CCR2 antagonist showed the smallest area of alveolar bone loss and were similar to the control group (group 3 vs. 4, p = 0.14). Qualitative analysis of fluorescent dye uptake indicated increased bone formation in CCR2-antagonist-treated mice, suggesting an improved bone repairing process. CONCLUSION: The results suggested that treatment with CCR2 antagonist inhibited alveolar bone loss and improved bone formation in this model. These data support further evaluation of CCR2 antagonist as a therapeutic target for the development of new treatment modalities on bacterially induced alveolar bone resorption.

Recent trends and clinical features of childhood vitamin D deficiency presenting to a children's hospital in Glasgow.

BACKGROUND: The incidence of vitamin D deficiency is unclear in the context of continuing demographic changes and the introduction of new public health measures. METHODS: All cases in which vitamin D deficiency was suspected as the primary cause of the clinical presentation were studied. RESULTS: Between 2002 and 2008, 160 cases of symptomatic vitamin D deficiency were identified with twice as many cases in 2008 (n, 42) as in the previous years. The median age of the cohort was 24 months (range 2 weeks-14 years).Three cases were recorded in children of European background, whereas the rest were in children of South Asian, Middle Eastern or sub-Saharan ethnic background. Presenting features included bowed legs in 64 (40%) and a fit in 19 (12%). In one infant, concerns were raised following a presentation with cardiac failure and hypocalcaemia. SUMMARY: Symptomatic vitamin D deficiency remains prevalent in the West of Scotland. There is a need for effective public health education, action and surveillance.

The growth hormone insulin-like growth factor 1 axis in children and adolescents with inflammatory bowel disease and growth retardation.

CONTEXT: There is scarce knowledge about the growth hormone (GH) insulin-like growth factor-1 (IGF1) axis in children & adolescents with inflammatory bowel disease (IBD) and growth retardation. OBJECTIVE: To describe the pattern of GH and IGF1 secretion in children & adolescents with IBD. DESIGN: A retrospective review of 28 patients (23 M) of IBD (25 Crohn's Disease and three Ulcerative Colitis) and growth retardation who had investigation of the GH/IGF-1 axis. Height velocity (HV) and serum IGF1 were converted to standard deviation score (SDS); to account for delayed puberty in girls over 11 years and boys over 12 years, HV and serum IGF1 SDS were adjusted for bone age. RESULTS: Median (range) age and Ht SDS at the time of endocrine evaluation was 14.3 years (7.7,17.0) and -2.0(-3.6,-0.9), respectively. Median HVSDS over the prior 12 months was -2.2(-7.7,2.8). Median peak serum GH on insulin tolerance test (ITT) was 5.8 mcg/l (1.3, 24.0), and median serum IGF1 SDS was -0.9(-3.1, 0.1). Five of 28 (18%) had a peak serum GH of >12 mcg/l. Overall, four had biochemical evidence of functional GH deficiency (peak GH < 3 mcg/l and IGF1 SDS < 0) and 11 children had biochemical evidence suggesting GH resistance (peak GH > 6 mcg/l and IGF1 SDS < 0). However, only one child had a peak serum GH > 6 mcg/l and a very low IGF1 SDS of <-2.0. There was a negative association between peak serum GH and Ht SDS (r = -0.49, P = 0.008), but there was no association with HV and there was no association between IGF1 SDS and Ht or HV SDS. IGF1 SDS showed a negative association with erythrocyte sedimentation rate (r = -0.41, P = 0.04). CONCLUSION: Growth retardation in children and adolescents with IBD is commonly associated with a range of biochemical abnormalities ranging from functional GH deficiency to GH resistance. In these children, poor relationship between systemic markers of growth and height velocity point to an important role of growth factors at the target organ level in modulating growth in children with IBD. The value of assessing the GH/IGF-1 axis and whether it predicts subsequent response to growth-promoting therapy requires further exploration.

Characterization of the invasive and inflammatory traits of oral Campylobacter rectus in a murine model of fetoplacental growth restriction and in trophoblast cultures.

Campylobacter species (C. jejuni, C. fetus) are enteric abortifacient bacteria in humans and ungulates. Campylobacter rectus is a periodontal pathogen associated with human fetal exposure and adverse pregnancy outcomes including preterm delivery. Experiments in pregnant mice have demonstrated that C. rectus can translocate from a distant site of infection to the placenta to induce fetal growth restriction and impair placental development. However, placental tissues from human, small-for-gestational age deliveries have not been reported to harbor C. rectus despite evidence of maternal infection and fetal exposure by fetal IgM response. This investigation examined the temporal relationship between the placental translocation of C. rectus and the effects on fetal growth in mice. BALB/c mice were infected at gestational day E7.5 to examine placental translocation of C. rectus by immunohistology. C. rectus significantly decreased fetoplacental weight at E14.5 and at E16.5. C. rectus was detected in 63% of placentas at E14.5, but not at E16.5. In in vitro trophoblast invasion assays, C. rectus was able to effectively invade human trophoblasts (BeWo) but not murine trophoblasts (SM9-1), and showed a trend for more invasiveness than C. jejuni. C. rectus challenge significantly upregulated both mRNA and protein levels of IL-6 and TNFalpha in a dose-dependent manner in human trophoblasts, but did not increase cytokine expression in murine cells, suggesting a correlation between invasion and cytokine activation. In conclusion, the trophoblast-invasive trait of C. rectus that appears limited to human trophoblasts may play a role in facilitating bacterial translocation and placental inflammation during early gestation.

Owner's perception of carboplatin in conjunction with other palliative treatments for cancer therapy.

OBJECTIVES: To determine owner's perception of their pet's quality of life during treatment with carboplatin for a variety of canine and feline neoplasms. METHODS: Owners were contacted via a postal questionnaire and asked questions regarding their perception of chemotherapy in pets and their perception of carboplatin treatment in their pet. RESULTS: Twenty-eight (59%) of owners responded to the questionnaire. Forty-three percent of owners had not considered chemotherapy in pets before treatment; however, after treatment, 89% of owners supported its use. Sixteen (57%) patients had mild to severe side effects. Most patients experienced mild side effects, including lethargy and loss of appetite. Quality of life during treatment was reduced compared with prediagnosis quality of life however at its best was significantly improved compared with pretreatment quality of life. Eighty-nine per cent of respondents did not regret treating their pet. CLINICAL SIGNIFICANCE: Carboplatin is well tolerated by both owners and pets. Most patients have either no side effects or experience mild lethargy or inappetence. Carboplatin treatment, either alone or in conjunction with other medications, should be considered as a palliative treatment in both dogs and cats with susceptible neoplasms.

The concordance between serum anti-Mullerian hormone and testosterone concentrations depends on duration of hCG stimulation in boys undergoing investigation of gonadal function.

BACKGROUND: In boys undergoing investigation of gonadal function, the relationship between a single measurement of serum anti-Mullerian hormone (AMH) and hCG stimulated serum testosterone is unclear. AIM: The aim of the study was to assess concordance between serum AMH and testosterone concentrations following hCG stimulation of two different durations. METHODS: Samples from 284 children (M : F, 154 : 130) with a median age of 8 years (10th, 90th centiles, 0.25, 14) were used to establish an AMH reference range. Clinical data were reviewed in boys undergoing investigation of gonadal function and who had an AMH measurement and a hCG stimulated (3-day or 3-week) (n = 26) testosterone. Of these 26 boys, 11 had combined genital anomalies, whereas the rest had conditions such as isolated hypospadias, undescended testes or microphallus. Normal testosterone response to hCG stimulation was defined as a level greater than 3.5 nmol at day 4 and 9.5 nmol/l at day 22. RESULTS: In the reference group, the 5th centile AMH for boys below 1 year was 215 pmol/l and between 1 and 8 years 180 pmol/l. The 95th centile for girls for these respective age groups was 30 pmol/l and 25 pmol/l. In those cases where serum testosterone concentrations were available at day 1, day 4 and day 22 of the 3 week-hCG test, five cases had a normal serum testosterone at day 4 and three cases only showed such a response by day 22. In those where serum AMH was less than 180 pmol/l, a poor testosterone response of less than 3.5 nmol was observed in approximately seven of eight (88%) cases with a 3-day hCG stimulation test or the 3-week test. An AMH of greater than 180 pmol/l was associated with a normal testosterone response at day 4 in 10 out of 15 (67%) cases and at day 22 in eight of 11 (73%) cases. However, a low serum testosterone concentration of less than 3.5 nmol after the 3-day hCG test was only associated with a likelihood of a low AMH in three of eight (37%) cases. With the 3-week hCG test, a low day 22 testosterone of 9.5 mmol/l or less was associated with a low AMH of 180 pmol/l or less in four of seven (57%) cases. CONCLUSION: In boys undergoing investigation of gonadal function, the concordance between AMH and testosterone is better at day 22 than day 4. A normal AMH may provide useful information on overall testicular function but does not exclude the need for an hCG stimulation test.

The Cataract National Dataset electronic multi-centre audit of 55,567 operations: updating benchmark standards of care in the United Kingdom and internationally.

AIMS: To pilot the use of the Cataract National Dataset (CND) using multi-centre data from Electronic Patient Record (EPR) systems and to demonstrate the ability of the CND to deliver certain of its intended benefits, including detailed preoperative profiling of cataract surgery patients and updating of benchmark standards of care in the NHS and beyond. METHODS: NHS departments using EPR systems to collect a minimum preoperative, anaesthetic, operative and postoperative data set, the CND, were invited to submit data, which were remotely extracted, anonymised, assessed for conformity and completeness, and analysed. RESULTS: Four-hundred and six surgeons from 12 NHS Trusts submitted data on 55,567 cataract operations between November 2001 and July 2006 (86% from January 2004). Mean age (SD) was 75.4 (10.4) years, 62.0% female. Surgery was for first eyes in 58.5%, under local anaesthesia in 95.5% and by phacoemulsification in 99.7%. Trainees performed 33.9% of operations. Preoperative visual acuity (VA) was 6/12 or better in 42.9% eyes overall, in 35.3% first eyes and in 55.3% second eyes. Complication rates included the following: posterior capsule rupture and/or vitreous loss of 1.92%, simple zonule dialysis of 0.46% and retained lens fragments of 0.18%. Postoperative VA of 6/12 or better (and 6/6 or better) was achieved for 91.0% (45.9%) of all eyes, 94.7% (51.0%) of eyes with no co-pathologies and 79.9% (30.2%) of eyes with one or more co-pathologies respectively. CONCLUSIONS: The CND is fit for purpose, is able to deliver useful benefits and can be collected as part of routine clinical care via EPR systems. This survey confirms shifts in practice since the 1997-1998 UK National Survey with full conversion to phacoemulsification, better preoperative acuity, a halving of the surgical 'index' benchmark complication of posterior capsule rupture and/or vitreous loss, and improved VA outcomes.

The Cataract National Dataset electronic multicentre audit of 55,567 operations: antiplatelet and anticoagulant medications.

AIMS: This study aims to establish the prevalence of aspirin, dipyridamole, clopidogrel, and warfarin use in patients undergoing cataract surgery, and to compare local anaesthetic and intraoperative complication rates between users and non-users. METHODS: The Cataract National Dataset was remotely extracted and anonymised on 55,567 operations at 12 NHS Trusts using electronic patient records (EPRs) between 2001 and 2006. RESULTS: This report analyses 48,862 of the 55,567 operations from the eight centres, which routinely recorded a drug history. In all, 28.1% of the 48,862 patients were taking aspirin, 5.1% warfarin, 1.9% clopidogrel, and 1.0% dipyridamole. The recording of any complication of a sharp needle or subtenon's cannula local anaesthetic block was increased in patients taking clopidogrel, 8.0% (P<0.0001) or warfarin, 6.2% (P=0.0026) vs non-users, 4.3%, but no increase in potentially sight-threatening complications was identified. The incidence of subconjunctival haemorrhage was increased in patients taking clopidogrel, 4.4% (P<0.0001) or warfarin, 3.7% (P<0.0001) vs non-users, 1.7%. The recording of any operative complication was increased in those taking clopidogrel, 7.3% (P=0.0002) vs non-users, 4.4%, but the haemorrhagic operative complications of choroidal/suprachoroidal haemorrhage and hyphaema were not significantly increased. The non-haemorrhagic complication of posterior capsular rupture (PCR) was increased in those taking clopidogrel, 3.23% (P=0.0057) vs non-users, 1.77%. CONCLUSIONS: Clopidogrel or warfarin use was associated with a significant increase in minor complications of sharp needle and subtenon's cannula local anaesthesia but was not associated with a significant increase in potentially sight-threatening local anaesthetic or operative haemorrhagic complications.

The Cataract National Dataset electronic multicentre audit of 55,567 operations: risk stratification for posterior capsule rupture and vitreous loss.

AIMS: To identify and quantify risk factors for posterior capsule rupture or vitreous loss or both (PCR or VL or both) during cataract surgery and provide a method of composite risk assessment for individual operations. METHODS: The Cataract National Dataset was extracted on 55,567 operations from 12 National Health Service (NHS) Trusts using an electronic patient record (EPR) system between November 2001 and July 2006. Risk indicators for variations in the rate of 'PCR or VL or both' were identified by univariate and multivariate analyses. Adjusted odds ratios (ORs) were used to formulate a composite 'bespoke' risk for individual cases. RESULTS: Overall 'PCR or VL or both' rate was 1.92% (95% CI=1.81-2.04%). Risk indicators for this complication were increasing age, male gender, presence of glaucoma, diabetic retinopathy, brunescent/white cataract, no fundal view/vitreous opacities, pseudo-exfoliation/phacodonesis, reducing pupil size, axial length > or = 26.0 mm, the use of the alpha-blocker doxazosin, inability to lie flat and trainee surgeons performing operations. Adjusted ORs for these variables are used to estimate overall composite risk across multiple risk indicators in the form of a predicted probability of PCR or VL or both. Predicted probability for this complication ranged from less than 0.75% to more than 75%, depending on risk profile of individual operations. CONCLUSIONS: Higher-risk cases can be predicted, thus better informing the consent process and allowing surgeons to take appropriate precautions. Case-mix is a major determinant of the probability of an intraoperative complication. A simple composite risk estimation system has been developed.

The Cataract National Dataset Electronic Multi-centre Audit of 55,567 operations: anaesthetic techniques and complications.

PURPOSE: The primary aim of this study was to detail anaesthetic techniques and complications for cataract surgery in the UK. METHODS: The Cataract National Dataset was extracted from 12 National Health Service Trusts that used the same electronic patient record system between November 2001 and July 2006 on a total of 55,567 cataract operations. RESULTS: Anaesthesia was administered by an ophthalmologist in 56.7% of the cases, a career anaesthetist in 42.1% of the cases, a clinical assistant anaesthetist in 0.3% of the cases, and staff were not recorded in 0.9% of the cases. Local anaesthesia (LA) was used in 95.5%, with topical anaesthesia alone in 22.3% (range by site, 0-99.8%), topical and intracameral in 4.7% (range, 0-24.1%), subtenons in 46.9% (range, 0-81.8%), peribulbar in 19.5% (range, 0-63.4%), and retrobulbar in 0.5% (range, 0-5.3%). One or more minor complications occurred in 4.3% of 38,058 local blocks administered by either sharp needle or subtenons (blunt) cannula. Minor complications were 2.3 times more common with subtenons blocks (P<0.001). Serious complications, defined as sight or life threatening occurred in 25 eyes, 0.066%, undergoing sharp needle or subtenons cannula blocks. Sharp needle techniques had a 2.5-fold increased risk of serious complications compared with subtenons cannula techniques (P=0.026). CONCLUSION: Subtenons anaesthesia was the most widely used anaesthetic technique for cataract surgery but wide variation existed by site. There was a low rate of reported LA complications. There was a statistically significant increased risk of serious complications with sharp needle anaesthesia compared with subtenons technique.

Ocular air gun injuries: a one-year surveillance study in the UK and Eire (BOSU). 2001-2002.

AIMS: The vulnerability of the eye means that ocular air gun injuries figure prominently in the medical literature. This Study reports the results of the first ocular air gun injury surveillance study. METHODS: Ocular air gun injuries were reported to the British Ophthalmic Surveillance Unit (BOSU; United Kingdom and Eire) for the period November 2001-December 2002 (13 months). Two questionnaires were used to collect demographic details, circumstances of injury, details of injuries, medical management and outcome. RESULTS: A total of 105 initial and 99 follow-up questionnaires were returned. Eighty-six ocular air gun injuries occurred during the last 12 months of surveillance yielding a corrected, estimated incidence of 91-115 injuries/year. Injuries were most frequent in August/September, and 90% (95/105) of victims were men with mean age of 17.5 years (74% under 18 years). In all, 40% (32/81) of injuries occurred at home and 53% (43/81) in a public place. 23% (19/84) of injuries were deliberate, 66% (69/104) of injuries were severe and 20% (21/105) resulted in ruptured globes. In all, 54% (48/89) required hospital admission and 41 required surgery. A total of 11% (12/105) of eyes were either enucleated or eviscerated. Final visual acuity was 6/12 (Snellen) in 65% (59/91). Moderate/significant cosmetic deformities were recorded in 10% (8/77) and restricted ocular movements in 5% (4/72). CONCLUSIONS: Ocular air gun injuries damage sight and leave lasting morbidity. The demographics and circumstances of injury are well documented with access to, and unsupervised use of, air guns, appearing the principal risks for injury.

Best practice in primary care pathology: review 6.

This sixth best practice review examines four series of common primary care questions in laboratory medicine: (1) laboratory monitoring in hypertension and heart failure abnormalities; (2) markers of inflammatory joint disease; (3) laboratory investigation of chronic diarrhoea; and (4) mumps and chickenpox. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.

Investigation of global developmental delay.

The investigation of global developmental delay in preschool children varies between centres and between paediatricians. Following a literature search and review of the evidence base, guidelines were developed to assist in the assessment and management of such children presenting to secondary level services. Evidence supporting the use of genetic and biochemical investigations on a screening basis was found, but there was no evidence to support the use of metabolic investigations or neuroimaging in the absence of other positive findings on history or examination. Detailed history and examination are paramount in the assessment of children with global developmental delay. Investigations can be a useful adjunct in determining aetiology. Evidence based guidelines have been developed to assist doctors in the selection of appropriate investigations for this group of children.

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone.

BACKGROUND AND AIMS: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose. METHODS: Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l). RESULTS: A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day. CONCLUSION: Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Carotenaemia in children is common and benign: most can stay at home.

We identified children with elevated plasma carotene levels who attended the Royal Hospital for Sick Children, Glasgow, between July 1998 and April 2001 and carried out a retrospective case record review. Thirty-one children were identified (7 boys; 14 girls) with a median age at presentation of 13 months (range 7m- 11yrs). Twenty-seven (87%) children had simple diet-related carotenaemia and were well. In four cases the hypercarotenaemia reflected nutritional problems with associated failure to thrive. In only one case did the family doctor recognise the condition before referral. Many who attended hospital had laboratory confirmation of the benign diagnosis despite a clear dietary origin. Some had repeat laboratory tests to confirm resolution. Diet-related carotenaemia appears common in our community. The condition appears poorly recognised within primary care and hospital investigations may be over-enthusiastic.