A longitudinal, observational study examining the relationships of patient satisfaction with services and mental well-being to their clinical course in young people with Type 1 diabetes mellitus during transition from child to adult health services

AIM: We hypothesized that participant well-being and satisfaction with services would be positively associated with a satisfactory clinical course during transition from child to adult health care. METHODS: Some 150 young people with Type 1 diabetes mellitus from five diabetes units in England were recruited to a longitudinal study of transition. Each young person was visited at home four times by a research assistant; each visit was 1 year apart. Satisfaction with services (Mind the Gap; MTG) and mental well-being (Warwick-Edinburgh Mental Well-being Scale; WEMWBS) were captured. Change in HbA1c , episodes of ketoacidosis, clinic and retinal screening attendance were used to assess clinical course. In total, 108 of 150 (72%) young people had sufficient data for analysis at visit 4. RESULTS: Mean age at entry was 16 years. By visit 4, 81.5% had left paediatric healthcare services. Median HbA1c increased significantly (P = 0.01) from 69 mmol/mol (8.5%) at baseline to 75 mmol/mol (9.0%) at visit 4. WEMWBS scores were comparable with those in the general population at baseline and were stable over the study period. MTG scores were also stable. By visit 4, some 32 individuals had a 'satisfactory' and 76 a 'suboptimal' clinical course. There were no significant differences in average WEMWBS and MTG scores between the clinical course groups (P = 0.96, 0.52 respectively); nor was there a significant difference in transfer status between the clinical course groups. CONCLUSIONS: The well-being of young people with diabetes and their satisfaction with transition services are not closely related to their clinical course. Investigating whether innovative psycho-educational interventions can improve the clinical course is a research priority

The iBRA (implant breast reconstruction evaluation) study: protocol for a prospective multi-centre cohort study to inform the feasibility, design and conduct of a pragmatic randomised clinical trial comparing new techniques of implant-based breast reconstruction.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure in the UK. The introduction of techniques to augment the subpectoral pocket has revolutionised the procedure, but there is a lack of high-quality outcome data to describe the safety or effectiveness of these techniques. Randomised controlled trials (RCTs) are the best way of comparing treatments, but surgical RCTs are challenging. The iBRA (implant breast reconstruction evaluation) study aims to determine the feasibility, design and conduct of a pragmatic RCT to examine the effectiveness of approaches to IBBR. METHODS/DESIGN: The iBRA study is a trainee-led research collaborative project with four phases:Phase 1 - a national practice questionnaire (NPQ) to survey current practicePhase 2 - a multi-centre prospective cohort study of patients undergoing IBBR to evaluate the clinical and patient-reported outcomesPhase 3- an IBBR-RCT acceptability survey and qualitative work to explore patients' and surgeons' views of proposed trial designs and candidate outcomes.Phase 4 - phases 1 to 3 will inform the design and conduct of the future RCT All centres offering IBBR will be encouraged to participate by the breast and plastic surgical professional associations (Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons). Data collected will inform the feasibility of undertaking an RCT by defining current practice and exploring issues surrounding recruitment, selection of comparator arms, choice of primary outcome, sample size, selection criteria, trial conduct, methods of data collection and feasibility of using the trainee collaborative model to recruit patients and collect data. DISCUSSION: The preliminary work undertaken within the iBRA study will determine the feasibility, design and conduct of a definitive RCT in IBBR. It will work with the trainee collaborative to build capacity by creating an infrastructure of research-active breast and plastic surgeons which will facilitate future high-quality research that will ultimately improve outcomes for all women seeking reconstructive surgery. TRIAL REGISTRATION: ISRCTN37664281

Dietary intakes of women with Type 1 diabetes before and during pregnancy: A pre‐specified secondary subgroup analysis among CONCEPTT participants

Aim To describe the dietary intakes of women with Type 1 diabetes before and during pregnancy. Methods This was a pre‐specified subgroup analysis of CONCEPTT involving 63 women planning pregnancy and 93 pregnant women from 14 sites in England, Scotland and Ireland. Two hundred and forty‐six 3‐day food diaries (104 planning pregnancy, 142 pregnant) were matched to data source and food reference codes, and analysed using dietary software. Participants were informed that food diaries would be de‐identified and used only for research purposes. Results Mean (sd) daily energy intake was 1588 (346) kcal and 1673 (384) kcal in women planning pregnancy and pregnant women respectively. Total carbohydrate intake was consistent with dietary guideline recommendations [180 (52) g planning pregnancy, 198 (54) g pregnant], but non‐recommended sources (e.g. sugars, preserves, confectionery, biscuits, cakes) contributed to 46% of total daily carbohydrate intake. Fat consumption exceeded guideline recommendations [70 (21) g planning pregnancy, 72 (21) g pregnant]. Fibre [15.5 (5.3) g planning pregnancy, 15.4 (5.1) g pregnant], fruit and vegetable intakes [3.5 (2.2) and 3.1 (1.8) serves/day] were inadequate. Twelve women planning pregnancy (19%) and 24 pregnant women (26%) did not meet micronutrient requirements. Conclusions The diets of pregnant women from England, Scotland and Ireland are characterized by high fat, low fibre and poor‐quality carbohydrate intakes. Fruit and vegetable consumption is inadequate, with one in four women at risk of micronutrient deficiencies. Further research is needed to optimize maternal nutrition for glycaemic control and for maternal and offspring health

Crystal structure of monomeric human β-2- microglobulin reveals clues to its amyloidogenic properties

Dissociation of human β-2-microglobulin (β(2)m) from the heavy chain of the class I HLA complex is a critical first step in the formation of amyloid fibrils from this protein. As a consequence of renal failure, the concentration of circulating monomeric β(2)m increases, ultimately leading to deposition of the protein into amyloid fibrils and development of the disorder, dialysis-related amyloidosis. Here we present the crystal structure of a monomeric form of human β(2)m determined at 1.8-Å resolution that reveals remarkable structural changes relative to the HLA-bound protein. These involve the restructuring of a β bulge that separates two short β strands to form a new six-residue β strand at one edge of this β sandwich protein. These structural changes remove key features proposed to have evolved to protect β sheet proteins from aggregation [Richardson, J.&Richardson, D. (2002) Proc. Natl. Acad. Sci. USA 99, 2754–2759] and replaces them with an aggregationcompetent surface. In combination with solution studies using (1)H NMR, we show that the crystal structure presented here represents a rare species in solution that could provide important clues about the mechanism of amyloid formation from the normally highly soluble native protein

A study of the perceived risks, benefits and barriers to the use of SDD in adult critical care units (the SuDDICU study)

Peer reviewedPublisher PD

Measuring parents’ experiences and satisfaction with care during very preterm birth: a questionnaire development study

Objective: To develop a questionnaire to assess parents’ experiences and satisfaction with care during very preterm birth. Design: Questionnaire development. Setting: Parents whose babies had been cared for at five tertiary neonatal units in England. Population: A total of 145 women who gave birth before 32 weeksof gestation, and 85 of their partners. Methods: A 30-item questionnaire was developed on the basis of qualitative interviews with parents of very preterm babies, a literature review and discussion with relevant experts. The questionnaire was posted to a second group of parents, and its reliability and validity were explored. Main outcome measures The Preterm Birth Experience and Satisfaction Scale (P-BESS) was correlated with two global questions measuring satisfaction with care during the birth. Internal consistency was measured using Cronbach’s a. Results: Parents of 458 babies were invited to take part and 147 (32%) responded. Two women and 22 partners were excluded or ineligible, leaving 145 women and 85 partners. Factor analysis produced three clear dimensions: Staff professionalism and empathy, Information and explanations, and Confidence in staff. The total scale and three subscales showed high reliability. Strong positive correlations were found between the questionnaire scales and the two global questions, indicating convergent validity. For women whose partners were present at the birth, a fourth factor was identified ‘Partner Involvement’. Conclusions: The P-BESS appears to be a valid measure of satisfaction with care during very preterm birth

Zika virus: New clinical syndromes and its emergence in the western hemisphere

Zika virus (ZIKV) had remained a relatively obscure flavivirus until a recent series of outbreaks accompanied by unexpectedly severe clinical complications brought this virus into the spotlight as causing an infection of global public health concern. In this review, we discuss the history and epidemiology of ZIKV infection, recent outbreaks in Oceania and the emergence of ZIKV in the Western Hemisphere, newly ascribed complications of ZIKV infection, including Guillain-Barré syndrome and microcephaly, potential interactions between ZIKV and dengue virus, and the prospects for the development of antiviral agents and vaccines

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

<p>Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.</p> <p>Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.</p> <p>Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].</p> <p>Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.</p&gt

The SPORTSMART study: a pilot randomised controlled trial of sexually transmitted infection screening interventions targeting men in football club settings

Background: Uptake of chlamydia screening by men in England has been substantially lower than by women. Non-traditional settings such as sports clubs offer opportunities to widen access. Involving people who are not medically trained to promote screening could optimise acceptability. Methods: We developed two interventions to explore the acceptability and feasibility of urine-based sexually transmitted infection (STI) screening interventions targeting men in football clubs. We tested these interventions in a pilot cluster randomised control trial. Six clubs were randomly allocated, two to each of three trial arms: team captain-led and poster STI screening promotion; sexual health adviser-led and poster STI screening promotion; and poster-only STI screening promotion (control/comparator). Primary outcome was test uptake. Results: Across the three arms, 153 men participated in the trial and 90 accepted the offer of screening (59%, 95% CI 35% to 79%). Acceptance rates were broadly comparable across the arms: captain-led: 28/56 (50%); health professional-led: 31/46 (67%); and control: 31/51 (61%). However, rates varied appreciably by club, precluding formal comparison of arms. No infections were identified. Process evaluation confirmed that interventions were delivered in a standardised way but the control arm was unintentionally ‘enhanced’ by some team captains actively publicising screening events. Conclusions: Compared with other UK-based community screening models, uptake was high but gaining access to clubs was not always easy. Use of sexual health advisers and team captains to promote screening did not appear to confer additional benefit over a poster-promoted approach. Although the interventions show potential, the broader implications of this strategy for UK male STI screening policy require further investigation

Three-dimensional Structure of L-2-Haloacid Dehalogenase from Xanthobacter autotrophicus GJ10 Complexed with the Substrate-analogue Formate

The L-2-haloacid dehalogenase from the 1,2-dichloroethane degrading bacterium Xanthobacter autotrophicus GJ10 catalyzes the hydrolytic dehalogenation of small L-2-haloalkanoic acids to yield the corresponding D-2-hydroxyalkanoic acids. Its crystal structure was solved by the method of multiple isomorphous replacement with incorporation of anomalous scattering information and solvent flattening, and was refined at 1.95-Å resolution to an R factor of 21.3%. The three-dimensional structure is similar to that of the homologous L-2-haloacid dehalogenase from Pseudomonas sp. YL (1), but the X. autotrophicus enzyme has an extra dimerization domain, an active site cavity that is completely shielded from the solvent, and a different orientation of several catalytically important amino acid residues. Moreover, under the conditions used, a formate ion is bound in the active site. The position of this substrate-analogue provides valuable information on the reaction mechanism and explains the limited substrate specificity of the Xanthobacter L-2-haloacid dehalogenase.