Comparison of ALitretinoin with PUVA as the first-line treatment in patients with severe chronic HAnd eczema (ALPHA):study protocol for a randomised controlled trial

Introduction Hand eczema (HE) is one of the most common skin disorders and an important cause for morbidity and occupational disability. The 1-year prevalence of HE is estimated to be up to 10% and it is estimated that 5%–7% of those develop severe chronic HE. However, current clinical evidence is not compelling enough to guide clinical practice. In a survey among 194 UK dermatologists the most frequent first choice approaches were psoralen combined with ultraviolet A (UVA) treatment (PUVA), oral steroids and alitretinoin (AL). When asked which strategy was most efficient for long-term outcome 20% of clinicians indicated they did not know; 43% of clinicians reported AL and 30% reported PUVA. Methods and analysis ALPHA is a multicentre, open, prospective, two-arm parallel group, randomised controlled trial comparing PUVA and AL with a planned sample size re-estimation. Between 500 and 780 participants will be randomised on a 1:1 basis. The physician’s global assessment (PGA) will direct treatment after randomisation, non-responders will be treated according to usual clinical practice; providing valuable pilot data on second line therapeutic approaches to inform future trials. Assessments will be conducted up to 52 weeks post randomisation. The primary outcome measure is the Hand Eczema Severity Index at 12 weeks. Secondary outcome measures include modified Total Lesion Symptom Score, PGA, time to relapse, patient reported outcome measures and DNA extraction and assessment of genetic variants. A substudy on molecular inflammatory mediators will provide information on subgroup specific treatment responses. Photographs will be taken and HE severity assessed by a central review panel

Better Outcomes for Older people with Spinal Trouble (BOOST) Trial: a randomised controlled trial of a combined physical and psychological intervention for older adults with neurogenic claudication, a protocol

Introduction Neurogenic claudication due to spinal stenosis is common in older adults. The effectiveness of conservative interventions is not known. The aim of the study is to estimate the clinical and cost-effectiveness of a physiotherapist-delivered, combined physical and psychological intervention. Methods and analysis This is a pragmatic, multicentred, randomised controlled trial. Participants are randomised to a combined physical and psychological intervention (Better Outcomes for Older people with Spinal Trouble (BOOST) programme) or best practice advice (control). Community-dwelling adults, 65 years and over, with neurogenic claudication are identified from community and secondary care services. Recruitment is supplemented using a primary care-based cohort. Participants are registered prospectively and randomised in a 2:1 ratio (intervention:control) using a web-based service to ensure allocation concealment. The target sample size is a minimum of 402. The BOOST programme consists of an individual assessment and twelve 90 min classes, including education and discussion underpinned by cognitive behavioural techniques, exercises and walking circuit. During and after the classes, participants undertake home exercises and there are two support telephone calls to promote adherence with the exercises. Best practice advice is delivered in one to three individual sessions with a physiotherapist. The primary outcome is the Oswestry Disability Index at 12 months. Secondary outcomes include the 6 Minute Walk Test, Short Physical Performance Battery, Fear Avoidance Beliefs Questionnaire and Gait Self-Efficacy Scale. Outcomes are measured at 6 and 12 months by researchers who are masked to treatment allocation. The primary statistical analysis will be by ‘intention to treat’. There is a parallel health economic evaluation and qualitative study

Presence of phage-plasmids in multiple serovars of Salmonella enterica

Evidence is accumulating in the literature that the horizontal spread of antimicrobial resistance (AMR) genes mediated by bacteriophages and bacteriophage-like plasmid (phage-plasmid) elements is much more common than previously envisioned. For instance, we recently identified and characterized a circular P1-like phage-plasmid harbouring a blaCTX-M-15 gene conferring extended-spectrum beta-lactamase (ESBL) resistance in Salmonella enterica serovar Typhi. As the prevalence and epidemiological relevance of such mechanisms has never been systematically assessed in Enterobacterales, in this study we carried out a follow-up retrospective analysis of UK Salmonella isolates previously sequenced as part of routine surveillance protocols between 2016 and 2021. Using a high-throughput bioinformatics pipeline we screened 47 784 isolates for the presence of the P1 lytic replication gene repL, identifying 226 positive isolates from 25 serovars and demonstrating that phage-plasmid elements are more frequent than previously thought. The affinity for phage-plasmids appears highly serovar-dependent, with several serovars being more likely hosts than others; most of the positive isolates (170/226) belonged to S. Typhimurium ST34 and ST19. The phage-plasmids ranged between 85.8 and 98.2 kb in size, with an average length of 92.1 kb; detailed analysis indicated a high amount of diversity in gene content and genomic architecture. In total, 132 phage-plasmids had the p0111 plasmid replication type, and 94 the IncY type; phylogenetic analysis indicated that both horizontal and vertical gene transmission mechanisms are likely to be involved in phage-plasmid propagation. Finally, phage-plasmids were present in isolates that were resistant and non-resistant to antimicrobials. In addition to providing a first comprehensive view of the presence of phage-plasmids in Salmonella, our work highlights the need for a better surveillance and understanding of phage-plasmids as AMR carriers, especially through their characterization with long-read sequencing

Use of health services by remote dwelling Aboriginal infants in tropical northern Australia: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Australia is a wealthy developed country. However, there are significant disparities in health outcomes for Aboriginal infants compared with other Australian infants. Health outcomes tend to be worse for those living in remote areas. Little is known about the health service utilisation patterns of remote dwelling Aboriginal infants. This study describes health service utilisation patterns at the primary and referral level by remote dwelling Aboriginal infants from northern Australia.</p> <p>Results</p> <p>Data on 413 infants were analysed. Following birth, one third of infants were admitted to the regional hospital neonatal nursery, primarily for preterm birth. Once home, most (98%) health service utilisation occurred at the remote primary health centre, infants presented to the centre about once a fortnight (mean 28 presentations per year, 95%CI 26.4-30.0). Half of the presentations were for new problems, most commonly for respiratory, skin and gastrointestinal symptoms. Remaining presentations were for reviews or routine health service provision. By one year of age 59% of infants were admitted to hospital at least once, the rate of hospitalisation per infant year was 1.1 (95%CI 0.9-1.2).</p> <p>Conclusions</p> <p>The hospitalisation rate is high and admissions commence early in life, visits to the remote primary health centre are frequent. Half of all presentations are for new problems. These findings have important implications for health service planning and delivery to remote dwelling Aboriginal families.</p

Single-cell whole-genome amplification technique impacts the accuracy of SNP microarray-based genotyping and copy number analyses

Methods of comprehensive microarray-based aneuploidy screening in single cells are rapidly emerging. Whole-genome amplification (WGA) remains a critical component for these methods to be successful. A number of commercially available WGA kits have been independently utilized in previous single-cell microarray studies. However, direct comparison of their performance on single cells has not been conducted. The present study demonstrates that among previously published methods, a single-cell GenomePlex WGA protocol provides the best combination of speed and accuracy for single nucleotide polymorphism microarray-based copy number (CN) analysis when compared with a REPLI-g- or GenomiPhi-based protocol. Alternatively, for applications that do not have constraints on turnaround time and that are directed at accurate genotyping rather than CN assignments, a REPLI-g-based protocol may provide the best solution

Medication related problems in ICU survivors: learning from a multi-centre programme

No abstract available

Kroppenstedtia pulmonis sp. nov. and Kroppenstedtia sanguinis sp. nov., isolated from human patients

Three human clinical strains (W9323T, X0209T and X0394) isolated from lung biopsy, blood and cerebral spinal fluid, respectively, were characterized using a polyphasic taxonomic approach. Comparative analysis of the 16S rRNA gene sequences showed the three strains belonged to two novel branches within the genus Kroppenstedtia: 16S rRNA gene sequence analysis of W9323T showed closest sequence similarity to Kroppenstedtia eburnea JFMB-ATE T (95.3 %), Kroppenstedtia guangzhouensis GD02T (94.7 %) and strain X0209T (94.6 %); sequence analysis of strain X0209T showed closest sequence similarity to K. eburnea JFMB-ATE T (96.4 %) and K. guangzhouensis GD02T (96.0 %). Strains X0209T and X0394 were 99.9 % similar to each other by 16S rRNA gene sequence analysis. The DNA-DNA relatedness was 94.6 %, confirming that X0209T and X0394 belong to the same species. Chemotaxonomic data for strains W9323T and X0209T were consistent with those described for the genus Kroppenstedtia: whole-cell peptidoglycan contained LLdiaminopimelic acid; the major cellular fatty acids were iso-C15 and anteiso-C15; and the major menaquinone was MK-7. Different endospore morphology and carbon utilization profiles of strains W9323T and X0209T supported by phylogenetic analysis enabled us to conclude that the strains represent two new species within the genus Kroppenstedtia, for which the names Kroppenstedtia pulmonis sp. nov. (type strain W9323T =DSM 45752 T) and Kroppenstedtia sanguinis sp. nov. (type strain X0209T =DSM 45749T=CCUG 38657 T) are proposed

CAG repeat not polyglutamine length determines timing of Huntington’s disease onset

Variable, glutamine-encoding, CAA interruptions indicate that a property of the uninterrupted HTT CAG repeat sequence, distinct from the length of huntingtin’s polyglutamine segment, dictates the rate at which Huntington’s disease (HD) develops. The timing of onset shows no significant association with HTT cis-eQTLs but is influenced, sometimes in a sex-specific manner, by polymorphic variation at multiple DNA maintenance genes, suggesting that the special onset-determining property of the uninterrupted CAG repeat is a propensity for length instability that leads to its somatic expansion. Additional naturally occurring genetic modifier loci, defined by GWAS, may influence HD pathogenesis through other mechanisms. These findings have profound implications for the pathogenesis of HD and other repeat diseases and question the fundamental premise that polyglutamine length determines the rate of pathogenesis in the “polyglutamine disorders.

Psychological distress during pregnancy in a multi-ethnic community: findings from the born in Bradford cohort study

Purpose: Antenatal anxiety and depression are predictive of future mental distress, which has negative effects on children. Ethnic minority women are more likely to have a lower socio-economic status (SES) but it is unclear whether SES is an independent risk factor for mental health in pregnancy. We described the association between maternal mental distress and socio-demographic factors in a multi-ethnic cohort located in an economically deprived city in the UK. Methods: We defined eight distinct ethno-language groups (total N = 8,454) and classified a threshold of distress as the 75th centile of within-group GHQ-28 scores, which we used as the outcome for univariate and multivariate logistic regression for each ethnic group and for the sample overall. Results: Financial concerns were strongly and independently associated with worse mental health for six out of the eight ethnic groups, and for the cohort overall. In some groups, factors such as working status, education and family structure were associated with worse mental health, but for others these factors were of little importance. Conclusions: The diversity between and within ethnic groups in this sample underlines the need to take into consideration individual social, migration and economic circumstances and their potential effect on mental health in ethnically diverse areas