Successful treatment approaches for tumoral calcinosis in children and young people: A condition of diverse pathogenesis.

BACKGROUND: Ectopic calcification is inappropriate biomineralization of soft tissues occurring due to genetic or acquired causes of hyperphosphataemia and rarely in normophosphataemic individuals. Tumoral Calcinosis (TC) is a rare metabolic bone disorder commonly presenting in childhood and adolescence with periarticular extra-capsular calcinosis. Three subtypes of TC have been recognised: primary hyperphosphataemic familial TC (HFTC), primary normophosphataemic familial TC and secondary TC most commonly seen in chronic renal failure. In the absence of established treatment, management is challenging due to variable success rates with medical therapies and recurrence following surgery. AIM: We outline the successful treatment approaches in four children with TC (2 normophosphatemic TC, 2 HFTC) aged 2.5-10 years at initial presentation. CASES: Patient 1 (P1) presented at 10 years with a painless lump behind the right knee, P2 with swelling of the right knee anteriorly at 9 years, P3 and P4 with pain and swelling over the right elbow at 5 and 2.5 years respectively. All patients were of Black African-Caribbean origin and were previously reported to be fit and well with no family history of TC. RESULTS: P1, P2 had normophosphataemic TC and P3, P4 had HFTC with genetically confirmed GALNT3 mutation. All four patients had initial surgical resection with TC confirmed on histology. P1 had complete surgical resection with no recurrence at 27 months post-operatively. P2 had significant overgrowth of the tumour following surgery and was subsequently successfully managed with 25 % topical sodium metabisulphite (total duration of 8 months with a 4 month gap during which there was recurrence). P3 had post-surgical recurrence of TC on the right elbow and a new lesion on left elbow which resolved with oral acetazolamide monotherapy (15-20 mg/kg/day). P4 had recurrence of right elbow lesion following surgery and developed an extensive new hip lesion on sevelamer therapy which resolved completely with additional acetazolamide therapy (18-33 mg/kg/day). Acetazolamide was well tolerated with normal growth for 5 years in P3 and 6.5 years in P4 and no recurrence of lesions. CONCLUSION: The frequent post-surgical recurrence in TC and successful medical therapy on the other hand indicates that medical management as first line therapy should be adopted. Monotherapies with topical 25 % sodium metabisulphite in normophosphataemic and oral acetazolamide in HFTC are effective treatment strategies which are well tolerated.

Cessation of ambulation results in a dramatic loss of trabecular bone density in boys with Duchenne muscular dystrophy (DMD).

Glucocorticoids are currently used to improve muscle strength and prolong ambulation in boys with DMD although the effect on bone health is still unclear. The aim of this study was to compare bone strength in healthy children and boys with DMD and investigate the interaction between diminished muscle function, loss of ambulation and high dose oral steroids, over a two year time frame. Fifty children were studied, 14 healthy boys (HB), 13 boys with DMD who remained ambulant (DMD-RA) and 23 boys with DMD who lost ambulation (DMD-LA). All boys with DMD had taken oral glucocorticoids. Peripheral quantitative computed tomography was used to measure bone geometry, density, strength and muscle mass of the non-dominant tibia and radius. Measurements were made at baseline, 12 and 24 months at the distal metaphysis and mid diaphysis sites. Differences between the three groups were evaluated using ANOVA and a repeated measures model. There were no significant differences in age between the groups: mean age was 9.4, 8.7 and 8.8 years for HB, DMD-RA and DMD-LA, respectively. There was no significant difference in steroid exposure between the DMD groups. However, boys who lost ambulation had significantly lower muscle function at baseline (North Star Ambulatory Assessment DMD-RA 23.6 vs. DMD-LA 18.8; p < 0.05). At baseline, healthy boys had significantly greater trabecular bone density at the distal radius /ulna (23%/27%) and distal tibia/fibula (30%/46%) than boys with DMD (p < 0.05). They also had significantly larger diaphyseal tibiae/fibulae (74%/36%) and radii/ulnae (49%/31%) with thicker corticies and consequently greater bone strength. In contrast, boys with DMD had greater cortical density (4%). Over time, there were small significant differences in the rate of change of both muscle and bone parameters between healthy boys and boys with DMD. For both ambulant and non-ambulant boys with DMD the greatest changes in cortical bone were evident at the tibia. After two years boys with DMD had on average, 63% less bone strength than healthy boys. However, the most strikingly significant difference was in trabecular bone density for boys who became non-ambulant. By 2 years non-ambulant DMD boys had 53% less trabecular bone density at distal tibia than their healthy age matched peers compared with boys who remained ambulant who had 27% less trabecular bone density. In conclusion, bone and muscle strength is reduced for all boys with DMD even while they remain ambulant. However, tibia trabecular bone density loss is significantly accelerated in DMD boys who lose independent ambulation compared to DMD boys who remain ambulant despite equivalent levels of corticosteroid exposure.

Monitoring response to conventional treatment in children with XLH: Value of ALP and Rickets Severity Score (RSS) in a real world setting.

INTRODUCTION: X-linked hypophosphataemia (XLH) is conventionally managed with oral phosphate and active vitamin D analogues. OBJECTIVES: To evaluate long term treatment response by assessing biochemical disease activity [serum alkaline phosphatase (ALP)], radiological rickets severity score (RSS), growth and morbidity in patients with XLH on conventional therapy and assess the correlation between serum ALP and RSS. METHODS: XLH patients from 3 UK tertiary centres with ≥3 radiographs one year apart were included. Data was collected retrospectively. The RSS was assessed from routine hand and knee radiographs and ALP z scores were calculated using age-specific reference data. RESULTS: Thirty-eight (male = 12) patients met the inclusion criteria. The mean ± SD knee, wrist and total RSS at baseline (median age 1.2 years) were 2.0 ± 1.2, 1.9 ± 1.2 and 3.6 ± 1.3 respectively; and at the most recent clinic visit (median age 9.0 years, range 3.3-18.9) were 1.6 ± 1.0, 1.0 ± 1.0 and 2.5 ± 1.5 respectively. The mean ± SD serum ALP z scores at baseline and the most recent visit were 4.2 ± 2.3 and 4.0 ± 3.3. Median height SDS at baseline and most recent visit were -1.2 and -2.1 (p = 0.05). Dental abscess, craniosynostosis, limb deformity requiring orthopaedic intervention and nephrocalcinosis were present in 31.5%, 7.9%, 31.6% and 42.1% of the cohort respectively. There was no statistically significant (p > 0.05) correlation between ALP z scores and knee (r = 0.07) or total (r = 0.12) RSS. CONCLUSIONS: Conventional therapy was not effective in significantly improving biochemical and radiological features of disease. The lack of association between serum ALP and rickets severity on radiographs limits the value of ALP as the sole indicator of rickets activity in patients receiving conventional therapy.

Elemental formula associated hypophosphataemic rickets.

OBJECTIVES: Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate®, an amino-acid based formula (AAF). METHODS: A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom. RESULTS: 10 cases were identified, over a 9 month period, all associated with Neocate® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate®. CONCLUSION: The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate®, especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children.

Growth, bone health & ambulatory status of boys with DMD treated with daily vs. intermittent oral glucocorticoid regimen.

Oral glucocorticoids (GC) preserve muscle strength and prolong walking in boys with Duchenne muscular dystrophy (DMD). Although vertebral fractures have been reported in boys taking GC, fracture rates for different GC regimes have not been investigated. The aim of this pragmatic longitudinal study was to compare growth, body mass, bone mineral density (BMD), vertebral fractures (VF) and ambulatory status in boys with DMD on daily (DAILY) or intermittent (INTERMITTENT), oral GC regimens. A convenience sample of 50 DMD boys from two centres was included in the study; 25 boys each were on the DAILY or INTERMITTENT regimen. Size adjusted lumbar spine BMD (LS BMAD), total body less head BMD (TBLH), by DXA and distal forearm bone densities by pQCT, GC exposure, VF assessment and ambulatory status were analysed at three time points; baseline, 1 and 2 years. At baseline, there were no differences in age, GC duration or any bone parameters. However, DAILY boys were shorter (height SDS DAILY = -1.4(0.9); INTERMITTENT = -0.8(1.0), p = 0.04) with higher BMI (BMI SDS DAILY = 1.5(0.9); INTERMITTENT = 0.8(1.0), p = 0.01). Over 2 years, DAILY boys got progressively shorter (delta height SDS DAILY = -0.9(1.1); INTERMITTENT = +0.1(0.6), p < 0.001). At their 2 year assessment, 5 DAILY and 10 INTERMITTENT boys were non-ambulant. DAILY boys had more VFs than INTERMITTENT boys (10 versus 2; χ2 p = 0.008). BMAD SDS remained unchanged between groups. TBLH and radius BMD declined significantly but the rate of loss was not different. In conclusion, there was a trend for more boys on daily GCs to remain ambulant but at the cost of more VFs, greater adiposity and markedly diminished growth. In contrast, boys on intermittent GCs had fewer vertebral fractures but there was a trend for more boys to loose independent ambulation.

The use of magnetically controlled growing rods in paediatric Osteogenesis Imperfecta with early onset, progressive scoliosis.

Osteogenesis Imperfecta (OI) is a condition of bone fragility and can present with early onset scoliosis that can cause respiratory complications in later life. The fear of instrumenting the spine in OI is the possibility of fracture either on primary insertion or subsequent lengthening. Magnetically controlled growing rods were inserted to control a scoliosis in a 6-year old with OI type IV. Fixation was obtained using pedicle screws proximally and distally with sublaminar bands around the ribs proximally. These rods have been remotely lengthened on multiple occasions over a 2-year period. This has controlled the scoliosis whilst also allowing the spine to grow. There are no complications to report. This case reports the use of magnetically controlled growth rods used to manage early onset scoliosis in OI. Frequent lengthening, achieving small increases in length on every occasion protects against the risk of fracture during the lengthening procedure.

Vertebral fractures assessment in children: Evaluation of DXA imaging versus conventional spine radiography.

Vertebral fracture assessment (VFA) by DXA is an accepted tool in adults. However, its use in children has not been assessed. The aim of this study was to evaluate DXA VFA and morphometric analysis (MXA) using a GE Lunar iDXA bone densitometer against spinal radiographic assessment (RA) for the identification of vertebral fractures in children. Spine RA and VFA (T3-L5) were acquired on the same day in 80 children. Forty children considered high risk for fracture by their metabolic bone specialist were referred for spinal RA. Another 40 children were recruited as part of a prospective fracture study and were considered low risk for vertebral fracture. Agreement between RA and VFA was assessed by an expert paediatric radiologist and two paediatricians with expertise in bone pathology. Agreement between RA and MXA was assessed by an expert paediatric radiologist, two clinical scientists and an experienced paediatric radiographer. Vertebrae were ranked as normal, mild, moderate or severe if they had <10%, 11-25%, 26-50% and >50% deformity, respectively. Levels of agreement were calculated using the Cohen kappa score. Evaluating the data from all readable vertebrae, 121 mild, 44 moderate and 16 severe vertebral fractures were identified; with 26, 8, and 5 subjects having at least one mild, moderate or severe fracture, respectively. Depending on rater, 92.8-94.8% of the vertebrae were evaluable by RA. In contrast, 98.4% were evaluable by VFA and only 83.6% were evaluable by MXA. Moderate agreement was found between raters for RA [kappa 0.526-0.592], and VFA [kappa 0.601-0.658] and between RA and VFA [kappa 0.630-0.687]. In contrast, only slight agreement was noted between raters for MXA [kappa 0.361-0.406] and between VFA and MXA [kappa 0.137-0.325]. Agreement substantially improved if the deformities were dichotomised as normal or mild versus moderate or severe [kappa 0.826-0.834]. For the detection of moderate and/or severe fractures the sensitivities & specificities were 81.3% & 99.3%, and 62.5% & 99.2% for VFA and MXA, respectively. This study demonstrates that VFA is as good as RA for detecting moderate and severe vertebral fractures. Given the significant radiation dose saving of VFA compared with RA, VFA is recommended as a diagnostic tool for the assessment of moderate or severe vertebral fracture in children.

Prevention and treatment of nutritional rickets.

Nutritional rickets continues to be a significant health problem for children worldwide with recent evidence of increasing incidence in many developed countries. It is due to vitamin D deficiency and/or inadequate dietary calcium intake with variation in the relative contributions of each of these dependant on environmental factors such a dietary intake and sunlight exposure. Key to the prevention of rickets is ensuring that pregnant women and their infants receive vitamin D supplementation with good evidence from randomised controlled trials that infants who receive 400iu daily can achieve levels of 25 hydroxyvitamin D of >50nmol/l. However, public health implementation of daily supplementation is more challenging with a need to revisit food fortification strategies to ensure optimal vitamin D status of the population. Treatment of nutritional rickets has traditionally been with vitamin D2 or D3, often given as a daily oral dose for several weeks until biochemical and radiological evidence of healing. However, other treatment regimes with single or intermittent high doses have also proved to be effective. It is now recognised that oral calcium either as dietary intake or supplements should be routinely used in conjunction with vitamin D for treatment.

An investigation into the use of multi-source feedback (MSF) as a work-based assessment tool.

INTRODUCTION: This study compared Specialist Trainees' (STs) hand-selected multi-source feedback (MSF) scores with those made by their clinical supervisors and explored perceptions of both those being assessed and those assessing. METHODS: Participating STs were asked to hand a mini-PAT questionnaire to a clinical colleague of their choice and also to their Clinical Supervisor. Statistical analysis was carried out on submitted paired assessments to determine any differences in responses between clinical supervisors and hand-chosen assessors. Semi-structured interviews were held with seven nurses, seven Consultants and six postgraduate doctors. RESULTS: Forty pairs of mini-PAT questionnaires were analysed. Hand-chosen assessors' ratings were significantly higher than those for clinical supervisors with respect to: "good clinical care" (p < 0.01), "good medical practice" (p < 0.05), "teaching and training" (p < 0.01), "relationship with patients" (p < 0.05) as well as for overall impression of the trainee (p < 0.05). Five themes were identified from interviews: validity of selecting assessors; anonymity of assessors; usefulness of feedback; the value of multi-professional assessors; and grading. DISCUSSIONS: There is a systematic difference in the assessment scores for trainees in MSF between clinical supervisors and hand-chosen assessors, the former scoring trainees more harshly. Grading was open to interpretation. This raised questions, especially from nurse interviewees regarding appropriate benchmarking.

Outcomes following prosthetic patch repair in newborns with congenital diaphragmatic hernia.

BACKGROUND: The anatomical defect in congenital diaphragmatic hernia (CDH) can usually be closed primarily but prosthetic patch repair may be required in newborns with a deficient diaphragm. High rates of patch failure and hernia recurrence (up to 50 per cent) have been reported. This study evaluated contemporary outcomes following patch repair of CDH at a UK paediatric surgical centre. METHODS: Medical records of newborns undergoing surgery for CDH between 1 February 1990 and 1 November 2010, and attending a multidisciplinary follow-up clinic, were examined. Operative details and patch utilization are reported. RESULTS: Of 118 newborns with CDH, 37 required a patch to the diaphragmatic defect. Gore-Tex® patches were used in 35 and biological Surgisis® patches in two. Eight babies additionally required an abdominal wall patch. Seven infants had an abdominal patch alone with primary diaphragm repair. A total of 102 infants (86·4 per cent) survived after surgery. Two early recurrences were both related to the use of biological patches, leading to revisional surgery with Gore-Tex® patch reconstruction. Diaphragmatic patch use was associated with a greater requirement for intensive cardiovascular and respiratory support, although there was no significant difference in mortality between patch versus primary diaphragm repair. The mortality rate was significantly higher among infants requiring abdominal wall patching (with or without a diaphragmatic patch): 40 per cent (6 of 15) versus 9·7 per cent (10 of 103) (P = 0·006). Postoperative survival rates for infants with a diaphragmatic patch alone, abdominal wall patch alone, and both abdominal and diaphragmatic patches were 86 per cent (25 of 29), 57 per cent (4 of 7) and 63 per cent (5 of 8) respectively. CONCLUSION: Prosthetic diaphragmatic hernia repair at this centre has a good outcome and low rate of recurrence (5 per cent). The recognition of an inadequate abdominal domain prenatally may additionally prove to be a useful marker for predicting increased mortality in newborns with CDH.

Diagnostic evaluation of bone densitometric size adjustment techniques in children with and without low trauma fractures.

UNLABELLED: Several established methods are used to size adjust dual-energy X-ray absorptiometry (DXA) measurements in children. However, there is no consensus as to which method is most diagnostically accurate. All size-adjusted bone mineral density (BMD) values were more diagnostically accurate than non-size-adjusted values. The greatest odds ratio was estimated volumetric BMD for vertebral fracture. INTRODUCTION: The size dependence of areal bone density (BMDa) complicates the use of DXA in children with abnormal stature. Despite several size adjustment techniques being proposed, there is no consensus as to the most appropriate size adjustment technique for estimating fracture risk in children. The aim of this study was to establish whether size adjustment techniques improve the diagnostic ability of DXA in a cohort of children with chronic diseases. METHODS: DXA measurements were performed on 450 children, 181 of whom had sustained at least one low trauma fracture. Lumbar spine (L2-L4) and total body less head (TBLH) Z-scores were calculated using different size adjustment techniques, namely BMDa and volumetric BMD for age (bone mineral apparent density (BMAD)); bone mineral content (BMC) and bone area for height; BMC for bone area; BMC for lean mass (adjusted for height); and BMC for bone and body size. RESULTS: Unadjusted L2-L4 and TBLH BMDa were most sensitive but least specific at distinguishing children with fracture. All size adjustments reduced sensitivity but increased post-test probabilities, from a pre-test probability of 40 % to between 58 and 77 %. The greatest odds ratio for fracture was L2-L4 BMAD for a vertebral fracture and TBLH for lean body mass (LBM) (adjusted for height) for a long bone fracture with diagnostic odds ratios of 9.3 (5.8-14.9) and 6.5 (4.1-10.2), respectively. CONCLUSION: All size adjustment techniques improved the predictive ability of DXA. The most accurate method for assessing vertebral fracture was BMAD for age. The most accurate method for assessing long bone fracture was TBLH for LBM adjusted for height.

Do trainees value feedback in case-based discussion assessments?

BACKGROUND: Feedback is important in learning, including in workplace-based assessments. AIM: To explore trainee's perceptions of the educational value of case-based discussions (CBDs) specifically focusing on feedback. METHODS: An online questionnaire and interviews obtaining detailed descriptions of paediatric trainees at UK specialist training levels 1 and 2 views and experiences were used. Qualitative data were analysed using a thematic framework analysis. RESULTS: Trainees viewed CBDs as educationally valuable, aiding reflective learning, improving decision making skills and effecting a change in practice. Opinions varied regarding how useful they found the feedback. Feedback was perceived as more valuable from assessors who had a positive attitude towards CBDs, understood the process and had experience in leading them. Time constraints and assessments performed in less suitable environments had a negative impact on feedback. Trainees felt the choice of case played an important role, with challenging cases resulting in more beneficial feedback. CONCLUSIONS: CBD assessments provide a new opportunity for good quality learning and feedback, providing there is a commitment to the educational aspects of the process by both trainer and trainee. Trainers being aware of the qualities of the discussions that result in successful feedback, could significantly improve their educational value.

Oxygen saturation profile in healthy preterm infants.

AIM: To establish a reference range for oxygen saturation (SpO(2)) in well preterm infants to guide home oxygen therapy using a pulse oximeter and Pulse Oximetry Data Analysis Software (PODS). METHODS: SpO(2) and heart-rate profiles of healthy preterm infants receiving mechanical ventilation for less than 6 h and supplemental oxygen for less than 48 h were monitored using a pulse oximeter. The stored data were downloaded from the monitor to a personal computer as individual files. Each infant's files of SpO(2) were subsequently displayed in graphic form, and a reference range was constructed using dedicated software, PODS. RESULTS: 43 infants were studied. The median value of all infants mean SpO(2) values was 95% (range 92-99%). The median duration of saturations less than 85% and between 85% and 90 % were 1% and 2% respectively. Using the study group median, 5th and 95th percentiles, a cumulative frequency curve of time against SpO(2) value was constructed (representing the reference range of SpO(2) profiles in healthy preterm infants). CONCLUSION: The SpO(2) reference range can be used as an easy and practical guide to compare SpO(2) profiles of infants on home oxygen therapy and guide their oxygen therapy.

Changing clinical practice: significant events that influence trainees' learning.

BACKGROUND: Changing behaviour as a result of learning from clinical practice is an important part of improving the quality of healthcare. The aims of this study were to investigate the educational influences that produce change in specialist trainees' clinical practice and to identify any differences in the types of learning recalled between trainees in primary and secondary care. METHODS: All 105 general practice trainees (GPSTs) and 100 first-year specialist trainees (STs) in one deanery were given the opportunity to take part in the study. There were three data collection phases: three focus groups followed by a questionnaire and 13 semi-structured interviews. The questionnaire was distributed to all first-year STs and GPSTs. Of these, 64 STs (32% of total sample) and 45 GPSTs (22.5% of total sample) completed the questionnaire. RESULTS: Broad themes outlining the key influences on behavioural change were practice-based learning and the adherence to guidelines. These themes were identified from the focus groups and questionnaire and explored during interviews. Both primary and secondary care trainees reported similar educational influences. CONCLUSIONS: There is no difference in the types of learning event that primary and secondary care trainees recall when describing changes in their clinical practice. Formal learning opportunities were valued when relevant to everyday clinical experiences. Guidelines were reference points in everyday practice and also a focus for discussion in formal education settings. Positive and negative clinical events were recognised to be key experiences that aided professional development and learning. These results support the use of work-place-based learning as a means of facilitating clinical change and development in specialty training in primary and secondary care.

Use of home oxygen for children in England and Wales.

BACKGROUND: With the introduction of a standardised ordering system in February 2006, the opportunity arose to collect data on children requiring home oxygen in England and Wales. The authors' aim was to determine the incidence and patterns of home oxygen prescribing. METHODS: A paediatric home oxygen clinical network and the Children's Home Oxygen Record Database were established. During a 3-year period (February 2006 to January 2009), prescribers were requested to submit copies of the Home Oxygen Order Forms. In addition, anonymised point prevalence data on all patients currently receiving home oxygen in June 2007 were obtained from the four provider companies. RESULTS: Children's Home Oxygen Record Database--Forms were analysed for 888 children <16 years (58% boys) with a median age of 4.1 months; 656 (74%) were <1 year. 541 (68%) had a diagnosis of chronic neonatal lung disease; 53 (7%), neurodisability; and 49 (6%), cardiac disease. Order forms were often incomplete, and prescribing practice was variable. Provider's cross-sectional survey--There were 3338 children <16 years, representing 4% of all patients on home oxygen. Median age was 3.1 years with a peak at 6 months. The prevalence for paediatric home oxygen use in England and Wales was 0.33 per 1000, with a peak of 1.08 per 1000 for those <1 year. Marked regional variation was noted. CONCLUSIONS: This is the first national dataset available for children prescribed home oxygen in England and Wales. The study emphasises the need for a coordinated approach to home oxygen prescribing and justifies the recent publication of evidence-based guidelines.