EXOGEN ultrasound bone healing system for long bone fractures with non-union or delayed healing: a NICE medical technology guidance

Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.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.The Birmingham and Brunel Consortium is funded by NICE to act as an External Assessment Centre for the Medical Technologies Evaluation Programme

Mutations in KDSR Cause Recessive Progressive Symmetric Erythrokeratoderma

Supplemental Data Supplemental Data include five figures and three tables and can be found with this article online at http://dx.doi.org/10.1016/j.ajhg.2017.05.003. Supplemental Data Document S1. Figures S1–S5 and Tables S1–S3 Download Document S2. Article plus Supplemental Data Download Web Resources 1000 Genomes, http://www.internationalgenome.org/ ANNOVAR, http://annovar.openbioinformatics.org/en/latest/ BWA-MEM, http://bio-bwa.sourceforge.net/index.shtml Database of Genomic Variants, http://dgv.tcag.ca/dgv/app/home dbSNP, https://www.ncbi.nlm.nih.gov/projects/SNP/ Exome Aggregation Consortium (ExAC) Browser, http://exac.broadinstitute.org/ ExonPrimer, https://ihg.helmholtz-muenchen.de/ihg/ExonPrimer.html GenBank, https://www.ncbi.nlm.nih.gov/genbank/ Genome Analysis Toolkit (GATK), https://software.broadinstitute.org/gatk/ Integrative Genomics Viewer (IGV), http://software.broadinstitute.org/software/igv/ OMIM, https://www.omim.org/ SNPmasker, http://bioinfo.ebc.ee/snpmasker/ UCSC Genome Browser, https://genome.ucsc.edu/index.html Variant Effect Predictor, http://useast.ensembl.org/info/docs/tools/vep/index.html The discovery of new genetic determinants of inherited skin disorders has been instrumental to the understanding of epidermal function, differentiation, and renewal. Here, we show that mutations in KDSR (3-ketodihydrosphingosine reductase), encoding an enzyme in the ceramide synthesis pathway, lead to a previously undescribed recessive Mendelian disorder in the progressive symmetric erythrokeratoderma spectrum. This disorder is characterized by severe lesions of thick scaly skin on the face and genitals and thickened, red, and scaly skin on the hands and feet. Although exome sequencing revealed several of the KDSR mutations, we employed genome sequencing to discover a pathogenic 346 kb inversion in multiple probands, and cDNA sequencing and a splicing assay established that two mutations, including a recurrent silent third base change, cause exon skipping. Immunohistochemistry and yeast complementation studies demonstrated that the mutations cause defects in KDSR function. Systemic isotretinoin therapy has achieved nearly complete resolution in the two probands in whom it has been applied, consistent with the effects of retinoic acid on alternative pathways for ceramide generation

Implementing pelvic floor muscle training in women's childbearing years: A critical interpretive synthesis of individual, professional, and service issues

Antenatal pelvic floor muscle training (PFMT) may be effective for the prevention and treatment of urinary and fecal incontinence both in pregnancy and postnatally, but it is not routinely implemented in practice despite guideline recommendations. This review synthesizes evidence that exposes challenges, opportunities, and concerns regarding the implementation of PFMT during the childbearing years, from the perspective of individuals, healthcare professionals (HCPs), and organizations.MethodsCritical interpretive synthesis of systematically identified primary quantitative or qualitative studies or research syntheses of women's and HCPs attitudes, beliefs, or experiences of implementing PFMT.ResultsFifty sources were included. These focused on experiences of postnatal urinary incontinence (UI) and perspectives of individual postnatal women, with limited evidence exploring the views of antenatal women and HCP or wider organizational and environmental issues. The concept of agency (people's ability to effect change through their interaction with other people, processes, and systems) provides an over?arching explanation of how PFMT can be implemented during childbearing years. This requires both individual and collective action of women, HCPs, maternity services and organizations, funders and policymakers.ConclusionNumerous factors constrain women's and HCPs capacity to implement PFMT. It is unrealistic to expect women and HCPs to implement PFMT without reforming policy and service delivery. The implementation of PFMT during pregnancy, as recommended by antenatal care and UI management guidelines, requires policymakers, organizations, HCPs, and women to value the prevention of incontinence throughout women's lives by using low?risk, low?cost, and proven strategies as part of women's reproductive health

Supported self-management for patients with COPD who have recently been discharged from hospital:a systematic review and meta-analysis

Purpose: Although many hospitals promote self-management to chronic obstructive pulmonary disease (COPD) patients post discharge from hospital, the clinical effectiveness of this is unknown. We undertook a systematic review of the evidence as part of a Health Technology Assessment review. Methods: A comprehensive search strategy with no language restrictions was conducted across relevant databases from inception to May 2012. Randomized controlled trials of patients with COPD, recently discharged from hospital after an acute exacerbation and comparing a self-management intervention with control, usual care or other intervention were included. Study selection, data extraction, and risk of bias assessment were undertaken by two reviewers independently. Results: Of 13,559 citations, 836 full texts were reviewed with nine randomized controlled trials finally included in quantitative syntheses. Interventions were heterogeneous. Five trials assessed highly supported multi-component interventions and four trials were less supported with fewer contacts with health care professionals and mainly home-based interventions. Total sample size was 1,466 (range 33–464 per trial) with length of follow-up 2–12 months. Trials varied in quality; poor patient follow-up and poor reporting was common. No evidence of effect in favor of self-management support was observed for all-cause mortality (pooled hazard ratio =1.07; 95% confidence interval [0.74 to 1.55]; I2=0.0%, [n=5 trials]). No clear evidence of effect on all-cause hospital admissions was observed (hazard ratio 0.88 [0.61, 1.27] I2=66.0%). Improvements in St George’s Respiratory Questionnaire score were seen in favor of self-management interventions (mean difference =3.84 [1.29 to 6.40]; I2=14.6%), although patient follow-up rates were low. Conclusion: There is insufficient evidence to support self-management interventions post-discharge. There is a need for good quality primary research to identify effective approaches

Genome-wide association of functional traits linked with<i> Campylobacter jejuni </i>survival from farm to fork

Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, primarily associated with the consumption of contaminated poultry. C. jejuni lineages vary in host range and prevalence in human infection, suggesting differences in survival throughout the poultry processing chain. From 7,343 MLST-characterised isolates, we sequenced 600 C. jejuni and C. coli isolates from various stages of poultry processing and clinical cases. A genome-wide association study (GWAS) in C. jejuni ST-21 and ST-45 complexes identified genetic elements over-represented in clinical isolates that increased in frequency throughout the poultry processing chain. Disease-associated SNPs were distinct in these complexes, sometimes organised in haplotype blocks. The function of genes containing associated elements was investigated, demonstrating roles for cj1377c in formate metabolism, nuoK in aerobic survival and oxidative respiration, and cj1368-70 in nucleotide salvage. This work demonstrates the utility of GWAS for investigating transmission in natural zoonotic pathogen populations and provides evidence that major C. jejuni lineages have distinct genotypes associated with survival, within the host specific niche, from farm to fork. </p