EXOGEN Ultrasound Bone Healing System for Long Bone Fractures with Non-Union or Delayed Healing: A NICE Medical Technology Guidance

A routine part of the process for developing National Institute for Health and Care Excellence (NICE) medical technologies guidance is a submission of clinical and economic evidence by the technology manufacturer. The Birmingham and Brunel Consortium External Assessment Centre (EAC; a consortium of the University of Birmingham and Brunel University) independently appraised the submission on the EXOGEN bone healing system for long bone fractures with non-union or delayed healing. This article is an overview of the original evidence submitted, the EAC’s findings, and the final NICE guidance issued.     

Determinants of uptake of home modifications and exercise to prevent falls in community‐dwelling older people

Objective: To examine the age‐specific population prevalence and predictors of uptake of home modifications and exercise to prevent falls in the NSW older population. Methods: A total of 5,681 respondents were asked questions on fall prevention activities as part of the 2009 NSW Falls Prevention Survey. Results were weighted to represent the NSW population. Regression analysis was used to determine factors associated with uptake of interventions. Results: Overall, 28.9% of the older population have modified their home, and 35.1% increased exercise to prevent falls. Main predictors of home modification were being aged 85+ (RR 2.04, 95% CI 1.76–2.35) and physiotherapy/occupational therapy intervention (RR 1.57, 95% CI 1.22–2.01). Main predictors of increasing exercise were physiotherapy/OT intervention (RR 2.12, 95% CI 1.86–2.42) and medical advice (RR 1.45, 95% CI1.32–1.60). Older respondents (RR 0.68, 95% CI 0.57–0.81) and those with fair/poor health (RR 0.86, 95% CI 0.77–0.96) were less likely to report increased exercise. Conclusion: More than one‐quarter of the older population of NSW report having made modifications to their home and one‐third increased exercise to prevent falls. There was a clear gradient of increased uptake of home modifications with increasing age, with the reverse trend for increased exercise. Implication: Although fall prevention initiatives are having an impact at the population level, targeted strategies for high‐risk groups are still required.     

Observation of Spontaneous Expressive Language (OSEL): A New Measure for Spontaneous and Expressive Language of Children with Autism Spectrum Disorders and Other Communication Disorders

A new language measure, the Observation of Spontaneous Expressive Language (OSEL), is intended to document spontaneous use of syntax, pragmatics, and semantics in 2–12-year-old children with Autism Spectrum Disorder (ASD) and other communication disorders with expressive language levels comparable to typical 2–5 year olds. Because the purpose of the OSEL is to provide developmental norms for use of language, the first step involves assessment of the scale’s feasibility, validity, and reliability using a sample of 180 2–5 year-old typically developing children. Pilot data from the OSEL shows strong internal consistency, high reliabilities and validity. Once replicated with a large population-based sample and in special populations, the scale should be helpful in designing appropriate interventions for children with ASD and other communication disorders.     

Esophageal Dysmotility After Laparoscopic Gastric Band Surgery

Background

The effect of the laparoscopic adjustable gastric band (LAGB) on the esophagus has been the subject of few studies despite recognition of its clinical importance. The aim of this study was to investigate the frequency and clinical effect of esophageal dysmotility and dilatation after LAGB.

Methods

We undertook a retrospective analysis of 50 consecutive patients with no dysmotility on perioperative video contrast swallow who underwent primary LAGB operation. All patients had serial focused postoperative contrast studies for band adjustments at least 6 months post-LAGB. Clinical and radiological outcomes were assessed.

Results

Median follow-up time was 18 months (range 7–39 months), and the median number of contrast swallows per patient was 5. The mean excess weight loss (EWL) overall was 47 % (standard deviation (SD) 22.3). Radiological abnormalities were recorded in 17 patients (34 %, 95 % confidence interval (CI) 21–49 %), of whom 15 had radiological dysmotility and 7 had esophageal dilatation (five patients had both dysmotility and dilatation). Of these 17 patients, six (35 %) developed significant symptoms of dysphagia, gastroesophageal reflux disease (GERD) or regurgitation requiring fluid removal. In comparison, 12 of 33 (36 %) patients without radiological abnormalities developed symptoms requiring fluid removal (p?=?1.00). Patients with radiological abnormalities were significantly older than those without these abnormalities. Symptoms were alleviated by removing fluid in most patients.

Conclusions

The LAGB operation results in the development of radiological esophageal dysmotility in a significant proportion of patients. It is not clear if these changes are associated with an increased risk of significant symptoms. Fluid removal can reverse these abnormalities and their associated symptoms.     

Language characterization in 16p11.2 deletion and duplication syndromes

Expressive language impairment is one of the most frequently associated clinical features of 16p11.2 copy number variations (CNV). However, our understanding of the language profiles of individuals with 16p11.2 CNVs is still limited. This study builds upon previous work in the Simons Variation in Individuals Project (VIP, now known as Simons Searchlight), to characterize language abilities in 16p11.2 deletion and duplication carriers using comprehensive assessments. Participants included 110 clinically ascertained children and family members (i.e., siblings and cousins) with 16p11.2 BP4‐BP5 deletion and 58 with 16p11.2 BP4‐BP5 duplication between the ages of 2–23 years, most of whom were verbal. Regression analyses were performed to quantify variation in language abilities in the presence of the 16p11.2 deletion and duplication, both with and without autism spectrum disorder (ASD) and cognitive deficit. Difficulties in pragmatic skills were equally prevalent in verbal individuals in both deletion and duplication groups. NVIQ had moderate quantifiable effects on language scores in syntax and semantics/pragmatics (a decrease of less than 1 SD) for both groups. Overall, language impairments persisted even after controlling for ASD diagnosis and cognitive deficit. Language impairment is one of the core clinical features of individuals with 16p11.2 CNVs even in the absence of ASD and cognitive deficit. Results highlight the need for more comprehensive and rigorous assessment of language impairments to maximize outcomes in carriers of 16p11.2 CNVs.     

The localisation of inflammatory cells and expression of associated proteoglycans in response to implanted chitosan

Implantation of a foreign material almost certainly results in the formation of a fibrous capsule around the implant however, mechanistic events leading to its formation are largely unexplored. Mast cells are an inflammatory cell type known to play a role in the response to material implants, through the release of pro-inflammatory proteases and cytokines from their α-granules following activation. This study examined the in vivo and in vitro response of mast cells to chitosan, through detection of markers known to be produced by mast cells or involved with the inflammatory response. Mast cells, identified as Leder stained positive cells, were shown to be present in response to material implants. Additionally, the mast cell receptor, c-kit, along with collagen, serglycin, perlecan and chondroitin sulphate were detected within the fibrous capsules, where distribution varied between material implants. In conjunction, rat mast cells (RBL-2H3) were shown to be activated following exposure to chitosan as indicated by the release of β-hexosaminidase. Proteoglycan and glycosaminoglycans produced by the cells showed similar expression and localisation when in contact with chitosan to when chemically activated. These data support the role that mast cells play in the inflammatory host response to chitosan implants, where mediators released from their α-granules impact on the formation of a fibrous capsule by supporting the production and organisation of collagen fibres.     

The current status of risk-stratified breast screening

Apart from high-risk scenarios such as the presence of highly penetrant genetic mutations, breast screening typically comprises mammography or tomosynthesis strategies defined by age. However, age-based screening ignores the range of breast cancer risks that individual women may possess and is antithetical to the ambitions of personalised early detection. Whilst screening mammography reduces breast cancer mortality, this is at the risk of potentially significant harms including overdiagnosis with overtreatment, and psychological morbidity associated with false positives. In risk-stratified screening, individualised risk assessment may inform screening intensity/interval, starting age, imaging modality used, or even decisions not to screen. However, clear evidence for its benefits and harms needs to be established. In this scoping review, the authors summarise the established and emerging evidence regarding several critical dependencies for successful risk-stratified breast screening: risk prediction model performance, epidemiological studies, retrospective clinical evaluations, health economic evaluations and qualitative research on feasibility and acceptability. Family history, breast density or reproductive factors are not on their own suitable for precisely estimating risk and risk prediction models increasingly incorporate combinations of demographic, clinical, genetic and imaging-related parameters. Clinical evaluations of risk-stratified screening are currently limited. Epidemiological evidence is sparse, and randomised trials only began in recent years.Subject terms: Breast cancer, Cancer epidemiology     

Ultrastructural identification of cells with dendritic cell appearance in atherosclerotic aorta of apolipoprotein E deficient mice

The present electron microscopic study was undertaken to see whether cells with a dendritic cell appearance accumulate in atherosclerotic lesions of apolipoprotein E (apoE) deficient mice. Atherosclerotic aortas from 7 eight-month old apoE deficient mice were examined. In atherosclerotic plaques as well as in the underlying media and adventitia, cells with a dendritic cell appearance including the presence of a unique tubulovesicular system were detected. The tubulovesicular system was most hypertrophied in their cellular processes where the continuous cisterns sometimes formed circular structures. The cells containing the tubulovesicular system lacked lysosomes and phagolysosomes and their cytoplasm was free of lipid inclusions. The present observations suggest that dendritic cells are involved in apoE deficient mouse atherosclerosis. ApoE deficient mice might be a useful model for investigating functions of dendritic cells in atherogenesis.     

C4 complement allotypes in juvenile dermatomyositis

Twenty probands with juvenile dermatomyositis and their relatives were studied to determine the inherited segregation patterns of class I, II, and III HLA region markers including C4A, C4B, Bf, and C2 complement polymorphisms. The extended haplotype B8, DR3, C4A*Q0, C4B*1, C2*C, and Bf*S was present in 13 of the 20 probands. Three other probands also carried a haplotype with a null allele for C4A and two further probands carried a null allele for C4B; only two probands had no detectable C4 null allele. These data confirm previous studies showing high frequencies of B8 and DR3 in patients with juvenile dermatomyositis, but show that there is a higher association with null alleles of C4. This suggests that the C4 genes are either themselves the disease-susceptibility genes or are in very strong linkage disequilibrium with such genes.