A schedule of gross motor development for children with Down syndrome.

BACKGROUND: Gross motor milestones for children who develop typically have been well established; however, norms for children with Down syndrome (DS) are uncertain. Without a developmental schedule for the gross motor development of children with DS, medical professionals are limited in their ability to identify if the development of a particular child with DS is delayed in comparison with his or her peers (i.e. other children with DS), assess when intervention is needed and answer the questions of parents regarding when their child can be expected to achieve developmental milestones. The objectives of this study are to: (1) provide health care professionals and early intervention providers with longitudinal data on the gross motor development of children with DS gathered prospectively; (2) contribute to the development of a definitive schedule of gross motor development for children with DS; (3) enable the identification of gross motor development that is delayed in comparison with other children with DS; and (4) help medical professionals address the questions of concerned parents who are anxious to know when their child will achieve gross motor skills such as sitting, crawling or walking. METHODS: Longitudinal data on 44 defined gross motor skills were collected on a large cohort of children with DS (n = 509) who received care at two referral centres that specialise in DS. Mastery was awarded when skills were observed directly by the physical therapist. Clinical data were retrospectively reviewed from a prospective patient clinic database and analysed. RESULTS: Specific age of mastery of gross motor skills was assessed. The mean, standard deviation and median age in months of gross motor skill achievement for children with DS, along with the 5th, 25th, 75th and 95th percentiles, are provided for birth to walking skills and post walking skills. No statistically significant gender-by-age group difference was observed in the 44 skills. CONCLUSIONS: This study provides a schedule of gross motor development for children with DS derived from data collected prospectively from a large population. The gross motor development of the child with DS can be assessed based on his or her performance relative to other children with DS enabling early identification of advanced, age appropriate or delayed development, allowing for appropriate referrals for targeted intervention.

Alterations in circulating lymphoid cell populations in systemic small vessel vasculitis are non-specific manifestations of renal injury.

Innate lymphocyte populations, such as innate lymphoid cells (ILCs), γδ T cells, invariant natural killer T (iNK T) cells and mucosal-associated invariant T (MAIT) cells are emerging as important effectors of innate immunity and are involved in various inflammatory and autoimmune diseases. The aim of this study was to assess the frequencies and absolute numbers of innate lymphocytes as well as conventional lymphocytes and monocytes in peripheral blood from a cohort of anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV) patients. Thirty-eight AAV patients and 24 healthy and disease controls were included in the study. Patients with AAV were sampled both with and without immunosuppressive treatment, and in the setting of both active disease and remission. The frequencies of MAIT and ILC2 cells were significantly lower in patients with AAV and in the disease control group compared to healthy controls. These reductions in the AAV patients remained during remission. B cell count and frequencies were significantly lower in AAV in remission compared to patients with active disease and disease controls. Despite the strong T helper type 2 (Th) preponderance of eosinophilic granulomatosis with polyangiitis, we did not observe increased ILC2 frequency in this cohort of patients. The frequencies of other cell types were similar in all groups studied. Reductions in circulating ILC2 and MAIT cells reported previously in patients with AAV are not specific for AAV, but are more likely to be due to non-specific manifestations of renal impairment and chronic illness. Reduction in B cell numbers in AAV patients experiencing remission is probably therapy-related.

Functional magnetic resonance imaging of story listening in adolescents and young adults with Down syndrome: evidence for atypical neurodevelopment.

BACKGROUND: Previous studies have documented differences in neural activation during language processing in individuals with Down syndrome (DS) in comparison with typically developing individuals matched for chronological age. This study used functional magnetic resonance imaging (fMRI) to compare activation during language processing in young adults with DS to typically developing comparison groups matched for chronological age or mental age. We hypothesised that the pattern of neural activation in the DS cohort would differ when compared with both typically developing cohorts. METHOD: Eleven persons with DS (mean chronological age = 18.3; developmental age range = 4-6 years) and two groups of typically developing individuals matched for chronological (n = 13; mean age = 18.3 years) and developmental (mental) age (n = 12; chronological age range = 4-6 years) completed fMRI scanning during a passive story listening paradigm. Random effects group comparisons were conducted on individual maps of the contrast between activation (story listening) and rest (tone presentation) conditions. RESULTS: Robust activation was seen in typically developing groups in regions associated with processing auditory information, including bilateral superior and middle temporal lobe gyri. In contrast, the DS cohort demonstrated atypical spatial distribution of activation in midline frontal and posterior cingulate regions when compared with both typically developing control groups. Random effects group analyses documented reduced magnitude of activation in the DS cohort when compared with both control groups. CONCLUSIONS: Activation in the DS group differed significantly in magnitude and spatial extent when compared with chronological and mental age-matched typically developing control groups during a story listening task. Results provide additional support for an atypical pattern of functional organisation for language processing in this population.

von Willebrand factor antigen, von Willebrand factor propeptide and ADAMTS13 activity in TIA or ischaemic stroke patients changing antiplatelet therapy.

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays). VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04). Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.

STEPS: lean thinking, theory of constraints and identifying bottlenecks in an emergency department.

This study aimed to identify the bottlenecks in patients' journeys through an emergency department (ED). For each stage of the patient journey, the average times were compared between two groups divided according to the four hour time frame and disproportionate delays were identified using a significance test These bottlenecks were evaluated with reference to a lean thinking value-stream map and the five focusing steps of the theory of constraints. A total of 434 (72.5%) ED patients were tracked over one week. Logistic regression showed that patients who had radiological tests, blood tests or who were admitted were 4.4, 4.1 and 7.7 times more likely, respectively, to stay over four hours in the ED than those who didn't The stages that were significantly delayed were the time spent waiting for radiology (p = 0.001), waiting for the in-patient team (p = 0.004), waiting for a bed (p < 0.001) and ED doctor turnaround time (p < 0.001).

Differences in the clinical presentation of Trisomy 21 with and without autism.

BACKGROUND: Autism occurs 10 times more often in children with Down syndrome than in the general population, but diagnosing co-occurring autism in Down syndrome with severe intellectual disability is challenging. The objective of this case-control study was to identify characteristics differentiating children with trisomy 21 with and without autism and to determine the extent to which severe cognitive impairment affects the measures of autism symptomatology. METHOD: Twenty children with trisomy 21 and autism (cases) were compared with children with trisomy 21 without autism (controls) matched on chronologic age, race and gender. Communication, cognitive and adaptive behaviour skills were assessed with standardized instruments. Medical history was reviewed and medical records were examined for early head growth. Scores on the diagnostic algorithm of the Autism Diagnostic Interview--Revised (ADI-R) were compared after adjusting for cognitive ability as measured by the Stanford-Binet (Fifth Edition) non-verbal change sensitive score. RESULTS: Cases performed significantly more poorly on all assessments. Mean case-control differences for matched pairs were all significant at P < 0.0001 for receptive and expressive language skills, cognitive skills and adaptive skills. Seven cases had a history of seizures compared with one control(P = 0.01). After adjusting for cognitive ability, the mean scores on the Reciprocal Social Interaction, Communication, and Restricted, Repetitive and Stereotyped Behaviours domains of the ADI-R diagnostic algorithm remained significantly higher in cases compared with controls (P < 0.0001). All participants had decreased head size consistent with Down syndrome, with no case-control differences. CONCLUSION: Children with trisomy 21 and autism have significantly more impaired brain function than children with trisomy 21 without autism. However, the deficits in the core domains of social reciprocity and communication, and the restricted and repetitive interests are not entirely explained by the more severe cognitive impairment. This autism phenotype in children with trisomy 21 which includes an increased risk for seizures may indicate a widespread loss of functional connectivity in the brain.

A single fast radio burst localized to a massive galaxy at cosmological distance.

Fast radio bursts (FRBs) are brief radio emissions from distant astronomical sources. Some are known to repeat, but most are single bursts. Nonrepeating FRB observations have had insufficient positional accuracy to localize them to an individual host galaxy. We report the interferometric localization of the single-pulse FRB 180924 to a position 4 kiloparsecs from the center of a luminous galaxy at redshift 0.3214. The burst has not been observed to repeat. The properties of the burst and its host are markedly different from those of the only other accurately localized FRB source. The integrated electron column density along the line of sight closely matches models of the intergalactic medium, indicating that some FRBs are clean probes of the baryonic component of the cosmic web.

Seizure frequency and characteristics in children with Down syndrome.

Seizures have not historically been considered a major component of Down syndrome. We examined the prevalence of epileptic seizures in 350 children and adolescents with Down syndrome evaluated at a regional center between 1985 and 1997. Results showed that 28 patients (8%) had epileptic seizures: 13 (47%) partial seizures; 9 (32%) infantile spasms, and 6 (21%) generalized tonic-clonic seizures. In the infantile spasm group, there was no relationship between the initial electroencephalogram (EEG) pattern and response to treatment or long-term seizure control, or between type of pharmacologic treatment (valproic acid, adrenocorticotropic hormone or both) and clinical remission, EEG normalization or long-term seizure control. Neurodevelopmental outcome was poor despite good seizure control in the infantile spasm group. This regional study reinforces the relative association of seizures and Down syndrome. A prospective study including a national/international registry with emphasis on developmental assessment and long-term follow up is warranted.

Detection of non-accidental injuries presenting at emergency departments.

OBJECTIVES: To investigate whether cases of possible non-accidental injury as identified using five risk indicators give rise to any subjective concerns of child abuse. METHODS: Questionnaires were completed by the triage nurse and attending doctor for every child attending the general hospitals of the North Western Health Board, with an injury, during a six month period. The questionnaires included an assessment of subjective concerns about the injury occurrence and five risk indicators of child abuse. RESULTS: Children presenting with an injury who had two or more positive indicators failed to raise subjective concerns in the attending emergency department staff. CONCLUSIONS: The introduction of a policy of identifying positive indicators from the five risk indicators of child abuse needs additional computer support within emergency departments.

A systematic review on the outcomes of correction of diastasis of the recti.

PURPOSE: Diastasis or divarication of the rectus abdominus muscles describes the separation of the recti, usually as a result of the linea alba thinning and stretching. This review examines whether divaricated recti should be repaired and tries to establish if the inherent co-morbidity associated with surgical correction outweighs the benefits derived. METHODS: EMBASE, MEDLINE and the Cochrane library were searched for ('divarication' OR 'diastasis') AND ('recti' OR 'rectus'). A standard data extraction form was used to extract data from each text. Due to the lack of randomised control trials, meta-analysis was not possible. RESULTS: Seven studies report that patient satisfaction was high following surgery. The most common complication seen was the development of a seroma. Other common complications included haematomas, minor skin necrosis, wound infections, dehiscence, post-operative pain, nerve damage and recurrence, the rate of which may be as high as 40%. CONCLUSIONS: Further studies are required to compare laparoscopic and open abdominoplasty techniques. Patients and physicians should be advised that correction is largely cosmetic, and although divarications may be unsightly they do not carry the same risks of actual herniation. Progressive techniques have resulted in risk reduction with no associated surgical mortality. However, the outcomes may be imperfect, with unsightly scarring, local sepsis and the possibility of recurrence.

A study of metatarsal fractures in children.

The purpose of our study was to document the sites and distribution of mid-foot and fore-foot fractures in children, relating them to the pattern of injury with particular reference to the first metatarsal. The clinical records and radiographs of 388 children with foot injuries were examined. A total of 62 metatarsal and seven tarsal fractures were identified in 60 children. The commonest fracture was of the fifth metatarsal, 45 per cent overall; 90 per cent of these children were over 10 years old. In children under 5 years old, first metatarsal fractures accounted for 73 per cent, but in children over 5 years old, these fractures accounted for only 12 per cent of the total. In all, 6.5 per cent of all fractures and 20 per cent of first metatarsal fractures went unrecognized at the initial attendance.

Prescribing and dispensing for drug misusers in primary care: current practice in Scotland.

BACKGROUND: Substitute prescribing has increased in Scotland, as in the rest of the UK. Both GPs and pharmacists are becoming increasingly involved in service provision for drug misusers, but anecdotal evidence has suggested considerable variation in prescribing and dispensing practice. OBJECTIVE: We aimed to gain baseline data on (i) current prescribing practice by medical practitioners and drug agencies, (ii) dispensing practice by community pharmacists across Scotland for the management of drug misuse and (iii) variations in practice between health boards. METHODS: A structured questionnaire was posted to all community pharmacies in Scotland (n = 1142), in order to gather information on prescribing from prescriptions held at the time of the survey and information on current dispensing practice in managing drug misusers. RESULTS: The response rate was 79%. Sixty-one per cent of pharmacists were currently dispensing drugs for the management of drug misuse. The most frequently prescribed drug was methadone, dispensed by 46% of pharmacists, followed by diazepam (37%), dihydrocodeine (26%) and temazepam (25%). Sixty-five per cent of methadone prescriptions were dispensed daily on request from the prescriber. Of the 3387 people receiving a methadone prescription, 32.9% had to consume their daily dose on the pharmacy premises under a pharmacist's supervision. Nineteen per cent of pharmacies currently provided a service to supervise the consumption of methadone by clients and a further 14% were prepared to but had no current demand. The proportion of prescriptions requiring supervision of methadone consumption varied considerably between health board areas. CONCLUSIONS: Methadone is the most widely prescribed drug for drug misuse across Scotland, but there is considerable variation between health board areas in how prescribing is managed. Prescribing practice should be revised locally, in a process involving GPs and pharmacists. Pharmacists have an important role in preventing drug misuse in primary care, but need further support to optimize good practice.

Prehospital cardiac arrest in Leicestershire: targeting areas for improvement.

OBJECTIVE: To identify the impact of advanced life support skills on outcome for prehospital cardiac arrest in a defined population and to assess the value of certain physiological variables in predicting the outcome in those successfully resuscitated in the accident and emergency (A&E) department; to identify areas for improvement in the outcome of such patients. DESIGN: Prospective 12 month study. SETTING: Leicestershire, United Kingdom. MAIN OUTCOME MEASURE: Survival to hospital discharge and status at 6 months. RESULTS: 266 patients were identified as having suffered a prehospital cardiac arrest; of these, 86 had their resuscitation attempt terminated in the community by a general practitioner and 180 were transferred to the A&E department of the Leicester Royal Infirmary. Of the latter, 159 were felt to be of cardiac aetiology, and 19 were eventually discharged from hospital. All survivors had experienced a witnessed cardiac arrest, ventricular fibrillation (VF) being identified as the initial rhythm. After adjusting for age and sex using logistic regression, the Glasgow coma score (GCS) was found to be associated with subsequent mortality (chi 2 = 18.22 on 2 df, P < 0.0001). Compared to a baseline GCS of 9-15, the relative odds of death for a GCS of 3 were 25.3 (95% confidence interval 4.3 to 149-9), while a GCS of 4-8 gave a relative odds of death of 12-18 (95% CI 1.8 to 80.2). No significant association was found between postarrest arterial pH and mortality. CONCLUSIONS: The immediate GCS on admission is a predictor of outcome and it is important to monitor its trend in the first 24 h. Multidisciplinary audit and joint guidelines with other specialties are important in optimising the care of these patients.