Reporting of paediatric osteoporotic vertebral fractures in Duchenne muscular dystrophy and potential impact on clinical management: the need for standardised and structured reporting.

BACKGROUND: In boys with Duchenne muscular dystrophy (DMD), initiation of bisphosphonate is recommended upon identification of moderate or severe vertebral fractures, even if asymptomatic. Clear radiological reporting is important for consistency of clinical interpretation and management. OBJECTIVES: To audit radiology reports of spine imaging for vertebral fracture assessment in DMD, and assess potential impact on diagnosis and management. MATERIALS AND METHODS: Lateral thoracolumbar spine imaging (71 lateral spine radiographs and 13 lateral dual energy absorptiometry spine image) in 84 boys with DMD performed across two centres. Anonymised radiology reports by paediatric radiologists were circulated to two neuromuscular clinicians and two endocrinologists. Clinicians determined if there was vertebral fracture, no vertebral fracture, or unclear interpretation. Endocrinologists also determined if bisphosphonate was indicated. A single observer (a clinician with expertise in vertebral fracture assessment) performed vertebral fracture assessment in 37 images and re-reported using a structured format. Structured reports were re-circulated to the four clinicians to re-evaluate the degree of concordance in clinical diagnosis of vertebral fracture and treatment decisions with bisphosphonate. RESULTS: The term "fracture" was used in 25/84 (30%) radiology reports and only in 8/43 (19%) with description of vertebral body abnormalities. Fracture grading was included in 7/43 (16%) radiology reports. Diagnostic concordance by the clinicians was noted in 36/84 (43%). Unclear interpretation was noted in 22% to 51% based on radiology reports. No unclear interpretation was noted with structured reports. Complete diagnostic (37/37, 100%) and treatment (37/37, 100%) concordance was noted with the structured reports, whereas complete diagnostic and treatment concordance was noted in only 16/37 (43%) and 17/37 (46%) of the radiology reports, respectively. CONCLUSION: Only a third of radiology reports of spine imaging in DMD explicitly used the terminology "fracture". Grading was only noted in a small percentage. Variability in diagnostic interpretation by clinicians may lead to differing management plans. As identification of vertebral fracture is a trigger for treatment, developing reporting guidelines for paediatric vertebral fracture assessment will improve care. A structured template should be introduced for radiological reporting of paediatric vertebral fracture assessment.

Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.

Importance: Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage. Objective: To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy. Design, Setting, and Participants: Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019). Interventions: Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66). Main Outcomes and Measures: The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017. Results: Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]). Conclusions and Relevance: Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy. Trial Registration: ClinicalTrials.gov Identifier: NCT01603407.

Cerebral thromboembolic events in pediatric patients with inflammatory bowel disease.

BACKGROUND: There is a recognized association between pediatric inflammatory bowel disease (IBD) and cerebral thromboembolic events (CTEs). Historical reporting had described the association as strongest between ulcerative colitis (UC), rather than Crohn's disease (CD). We describe the incidence and outcome of CTE in pediatric IBD patients from a single center over 5 years and the relative proportion of stroke reported in the literature in patients with UC and CD before and after January 2000. METHODS: Demographic data were extracted on all newly diagnosed cases of IBD in our center from January 2003 to January 2008 to ascertain patient characteristics, disease type, risk factors for CTE, modality of neuroimaging, and outcome. A literature search was performed to identify all articles describing stroke in pediatric IBD. All identified studies were stratified into those published before and after January 1 2000. RESULTS: In all, 154 new patients diagnosed with IBD (male 56%) (UC 30%, CD 64%, IBD unclassified [IBDU] 6%) were reviewed. Four cases of CTE occurred in our population over 5 years (2.6%). All patients had a risk factor for CTE. Fifteen case series were identified with 32 patients. There was a significant increase in the proportion strokes affecting patients with CD reported after January 2000 (P = 0.02). CONCLUSIONS: CTE affects a proportion of pediatric IBD patients. Although resolution of physical impairment is the norm, significant morbidity exists. Our study suggests a secular trend toward CTE in CD. Primary prevention with the identification and amelioration of identifiable risk factors should be the clinical objective in future studies.

Guillain-Barre syndrome occurring after adjuvant chemo-radiotherapy for endometrial cancer.

BACKGROUND: The association between Guillain-Barre syndrome (GBS) and malignancy is uncommon and has not been previously reported in gynecological cancers. CASE: Our case documents this syndrome occurring in a patient shortly after completion of adjuvant chemo-radiotherapy for endometrial carcinoma. We review the current literature and discuss potential pathogenic mechanisms of this likely paraneoplastic association. CONCLUSION: GBS in cancer patients is a potentially life-threatening condition and should be differentiated from simple chemotherapy toxicity, particularly as effective treatment is available.

Anoxic-epileptic seizures: observational study of epileptic seizures induced by syncopes.

AIMS: To describe a large series of children with anoxic-epileptic seizures (AES)--that is, epileptic seizures induced by syncopes. METHODS: Retrospective case-note review in a tertiary paediatric neurology unit. For all 27 children seen with a definite diagnosis of AES between 1972 and 2002, a review of clinical histories, videotapes, and EEG/ECG studies was undertaken. Main outcome measures were: age of onset, frequency and type of syncopes; age of onset and frequency of AES; type and duration of induced epileptic seizures; effect of treatment of syncopal and epileptic components. RESULTS: Median age of onset of syncopes was 8 months (range 0.2-120), frequency 2 in total to 40/day, median total approximately 200. Syncopes were predominantly reflex asystolic (RAS), prolonged expiratory apnoea (cyanotic breath-holding spells), or of mixed or uncertain origin; there was one each of ear piercing and hair grooming vasovagal syncope and one of compulsive Valsalva. Median age of onset of AES was 17 months (range 7-120), frequency from total 1 to 3/day, median total 3. The epileptic component was almost always bilateral clonic; three had additional epilepsy, one each with complex partial seizures, myoclonic absences, and febrile seizures plus. Median duration of epileptic component was 5 minutes (range 0.5-40, mean 11). Cardiac pacing prevented RAS in two patients: most other anti-syncope therapies were ineffective. Diazepam terminated the epileptic component in 6/8. Valproate or carbamazepine abolished AES in 5/7 without influencing syncope frequency. CONCLUSIONS: Although uncommon compared with simple syncopes, syncope triggered epileptic seizures (AES) are an important treatable basis of status epilepticus.

Bone mineral assessment by dual energy X-ray absorptiometry in children with inflammatory bowel disease: evaluation by age or bone area.

BACKGROUND: Abnormal linear growth and deficient bone mineral acquisition may coexist in children with inflammatory bowel disease (IBD). Traditionally, bone mineral assessment by dual energy x-ray absorptiometry (DXA) involves comparison to age- and gender-matched reference ranges, and these studies in children with IBD show a high prevalence of osteopenia. AIMS: To compare the prevalence of osteopenia using two methods of interpretation; one adjusted for age and gender and the other adjusted for bone size and gender. PATIENTS: Forty-seven patients with Crohn disease (CD) and 26 patients with ulcerative colitis (UC) with a median age of 13.5 years (range, 5.5-18.2 years) were evaluated. METHODS: Lumbar spine (LS) and total body (TB) bone mineral content (BMC) were measured by DXA and converted to bone mineral density (BMD, g/cm) corresponding to BMC divided by the bone area. Age and gender-matched BMD standard deviation scores (SDS) were based on reference data providing age- and gender-matched BMC and bone area. These data also allowed calculation of percentage of predicted bone area for age and gender (ppBone Area) and percentage of predicted BMC for Bone Area (ppBMC). RESULTS: Patients with CD were shorter than those with UC (median height, SDS, -0.9 v 0, P < 0.05). Median ppBone Area for LS and TB for the whole group was 85% (10th centile, 68; 90th centile 99) and 81% (10th centile 66; 90th centile, 97), respectively. The ppBone Area at both sites was directly related to height SDS and BMI SDS (r > 0.5; P < 0.005). Median BMD SDS for LS and TB was -1.6 (10th centile -3.6; 90th centile, -0.2) and -0.9 (10th centile, -2.4; 90th centile, 0.4), respectively. Median ppBMC for LS and TB was 98% (10th centile, 84%; 90th centile, 113%) and 101% (10th centile 94%; 90th centile, 107%), respectively. The ppBMC showed no relationship to ppBone Area (r = 0.1, NS). Failure to account for bone area led to a label of moderate or severe osteopenia in 65% of cases. After adjustment for bone area, the proportion of children with osteopenia fell to 22%. CONCLUSIONS: The data suggest that children with IBD often have small bones for age because they have growth retardation. When DXA data are interpreted with adjustment for bone size, most children were found to have adequate bone mass. Correct interpretation of DXA is important for identifying children who may be at a real risk of osteoporosis.

The GRAIL concept modelling language for medical terminology.

The GALEN representation and integration language (GRAIL) has been developed to support effective clinical user interfaces and extensible re-usable models of medical terminology. It has been used successfully to develop the prototype GALEN common reference (CORE) model for medical terminology and for a series of projects in clinical user interfaces within the GALEN and PEN&PAD projects. GRAIL is a description logic or frame language with novel features to support part-whole and other transitive relations and to support the GALEN modelling style aimed at re-use and application independence. GRAIL began as an experimental language. However, it has clarified many requirements for an effective knowledge representation language for clinical concepts. It still has numerous limitations despite its practical successes. The GRAIL experience is expected to form the basis for future languages which meet the same requirements but have greater expressiveness and more soundly based semantics. This paper provides a description and motivation for the GRAIL language and gives examples of the modelling paradigm which it supports.