Molecular epidemiology of human herpesvirus 8 in patients with HHV-8-related diseases in Ireland.

Human Herpesvirus 8 (HHV-8) has been classified by sequence analysis of open reading frame (ORF) K1, ORF K15, and variable sequence loci within the central constant region. The purpose of this study was to examine the molecular epidemiology of HHV-8 in an Irish population. This retrospective study included 30 patients who had HHV-8 DNA detected in plasma. Nested end-point PCR was used to characterise four regions of the HHV-8 genome, K1, T0.7 (K12), ORF 75, and K15. Sequencing data were obtained for 23 specimens from 19 patients. Phylogenetic analysis of ORF K1 demonstrated that subtypes A, B, C and F were present in 37%, 11%, 47% and 5%, respectively. For T0.7 and ORF 75, sequencing data were obtained for 12 patients. For T0.7, subtypes A/C, J, B, R and Q were present in 58%, 17%, 8%, 8%, and 8%, respectively. For ORF 75, subtypes A, B, C and D were present in 58%, 8%, 25%, and 8%, respectively. K15 sequences were determined for 13 patients. 69% had the P allele and 31% had the M allele. The data generated by this study demonstrate that a broad variety of HHV-8 subtypes are represented in patients exhibiting HHV-8-related disease in Ireland, a low prevalence country. The predominance of C and A K1 subtypes was as expected for a Western European population. The 31% prevalence for K15 subtype M was higher than expected for a Western European population. This may represent the changing and evolving epidemiology in Ireland due to altered migration patterns.

Development of a Novel Marine-Derived Tricomposite Biomaterial for Bone Regeneration.

Bone tissue engineering is a promising treatment for bone loss that requires a combination of porous scaffold and osteogenic cells. The aim of this study was to evaluate and develop a tricomposite, biomimetic scaffold consisting of marine-derived biomaterials, namely, chitosan and fucoidan with hydroxyapatite (HA). The effects of chitosan, fucoidan and HA individually and in combination on the proliferation and differentiation of human mesenchymal stem cells (MSCs) were investigated. According to the SEM results, the tricomposite scaffold had a uniform porous structure, which is a key requirement for cell migration, proliferation and vascularisation. The presence of HA and fucoidan in the chitosan tricomposite scaffold was confirmed using FTIR, which showed a slight decrease in porosity and an increase in the density of the tricomposite scaffold compared to other formulations. Fucoidan was found to inhibit cell proliferation at higher concentrations and at earlier time points when applied as a single treatment, but this effect was lost at later time points. Similar results were observed with HA alone. However, both HA and fucoidan increased MSC mineralisation as measured by calcium deposition. Differentiation was significantly enhanced in MSCs cultured on the tricomposite, with increased alkaline phosphatase activity on days 17 and 25. In conclusion, the tricomposite is biocompatible, promotes osteogenesis, and has the structural and compositional properties required of a scaffold for bone tissue engineering. This biomaterial could provide an effective treatment for small bone defects as an alternative to autografts or be the basis for cell attachment and differentiation in ex vivo bone tissue engineering.

In Vitro Degradation of 3D-Printed Poly(L-lactide-Co-Glycolic Acid) Scaffolds for Tissue Engineering Applications.

The creation of scaffolds for cartilage tissue engineering has faced significant challenges in developing constructs that can provide sufficient biomechanical support and offer suitable degradation characteristics. Ideally, such tissue-engineering techniques necessitate the fabrication of scaffolds that mirror the mechanical characteristics of the articular cartilage while degrading safely without damaging the regenerating tissues. The aim of this study was to create porous, biomechanically comparable 3D-printed scaffolds made from Poly(L-lactide-co-glycolide) 85:15 and to assess their degradation at physiological conditions 37 °C in pH 7.4 phosphate-buffered saline (PBS) for up to 56 days. Furthermore, the effect of scaffold degradation on the cell viability and proliferation of human bone marrow mesenchymal stem cells (HBMSC) was evaluated in vitro. To assess the long-term degradation of the scaffolds, accelerated degradation tests were performed at an elevated temperature of 47 °C for 28 days. The results show that the fabricated scaffolds were porous with an interconnected architecture and had comparable biomechanical properties to native cartilage. The degradative changes indicated stable degradation at physiological conditions with no significant effect on the properties of the scaffold and biocompatibility of the scaffold to HBMSC. Furthermore, the accelerated degradation tests showed consistent degradation of the scaffolds even in the long term without the notable release of acidic byproducts. It is hoped that the fabrication and degradation characteristics of this scaffold will, in the future, translate into a potential medical device for cartilage tissue regeneration.

The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels.

To create functional tissue engineering scaffolds, biomaterials should mimic the native extracellular matrix of the tissue to be regenerated. Simultaneously, the survival and functionality of stem cells should also be enhanced to promote tissue organisation and repair. Hydrogels, but in particular, peptide hydrogels, are an emerging class of biocompatible scaffolds which act as promising self-assembling biomaterials for tissue engineering and regenerative therapies, ranging from articular cartilage regeneration at joint defects, to regenerative spinal cord injury following trauma. To enhance hydrogel biocompatibility, it has become imperative to consider the native microenvironment of the site for regeneration, where the use of functionalised hydrogels with extracellular matrix adhesion motifs has become a novel, emerging theme. In this review, we will introduce hydrogels in the context of tissue engineering, provide insight into the complexity of the extracellular matrix, investigate specific adhesion motifs that have been used to generate functionalised hydrogels and outline their potential applications in a regenerative medicine setting. It is anticipated that by conducting this review, we will provide greater insight into functionalised hydrogels, which may help translate their use towards therapeutic roles.

A longitudinal multidimensional rehabilitation program for patients undergoing allogeneic blood and marrow transplantation (CaRE-4-alloBMT): Protocol for a phase II feasibility pilot randomized controlled trial.

BACKGROUND: Allogeneic blood and marrow transplantation (alloBMT) is a curative treatment for blood cancers associated with various treatment-related adverse events and morbidities. Current rehabilitation programs are limited for patients undergoing alloBMT and research is urgently needed to test the acceptability and effectiveness of these programs. In response, we developed a 6-month multidimensional longitudinal rehabilitation program that spans from pre transplant to 3 months post transplant discharge (CaRE-4-alloBMT). METHODS: This study is a phase II randomized controlled trial (RCT) conducted at the Princess Margaret Cancer Centre in patients undergoing alloBMT. A total of 80 patients stratified by frailty score will be randomized to receive usual care (n = 40) or CaRE-4-alloBMT plus usual care (n = 40). The CaRE-4-alloBMT program includes individualized exercise prescriptions, access to online education through a dedicated self-management platform, wearable technology for remote monitoring, and remote tailored clinical support. Feasibility will be assessed by examining the recruitment and retention rates and adherence to the intervention. Safety events will be monitored. Acceptability of the intervention will be assessed through qualitative interviews. Secondary clinical outcomes will be collected through questionnaires and physiological assessments at baseline (T0, 2-6 weeks pre-transplant), transplant hospital admission (T1), hospital discharge (T2), and 3 months post-discharge (T3). CONCLUSION: This pilot RCT study will determine the feasibility and acceptability of the intervention and study design and will inform full-scale RCT planning.

Comparing Factors Associated With Intimate Partner Violence Among Rural and Urban Women in Northern Uganda.

Intimate partner violence (IPV) is an important public health issue with negative effects at individual and societal levels. In northern Uganda, IPV prevalence is high but literature on it is limited. Northern Uganda has a long history of socio-economic and political upheavals, which are recognized risk factors for IPV. We compare IPV prevalence among rural and urban women in northern Uganda. This was a cross-sectional survey of 856 northern Ugandan women, 409 women living in rural areas, and 447 women working in an urban marketplace. Data were analyzed using logistic regression. High rates of emotional, physical, and sexual IPV were found. Almost four of five participants had experienced at least one type of IPV during their lifetime, and approximately half of the participants had experienced IPV in the 12 months prior to the survey. Many women stated that IPV was justified in certain situations. Younger age was a significant determinant of IPV in both cohorts (adjusted odds ratio [aOR] 0.95, 95% confidence interval [CI] [0.93-0.97]). Determinants of IPV among the rural cohort included male partner's alcohol abuse (aOR 2.22, CI [1.34-3.73]); having been in a physical fight with another man (aOR 1.90, 95% CI [1.12-3.23]); and controlling behaviors (aOR 1.21, CI [1.08-1.36]). Possible protective factors in the urban cohort included markers of economic empowerment such as being the decision maker on large household items (59.2% vs. 44.6%, p = .002) and having a mobile phone (20.4% vs. 12.4%, p = .024). Our study shows that IPV is a significant issue in northern Uganda. Economic empowerment is associated with lower rates of IPV in urban women, and interventions to reduce gender wealth inequality may reduce IPV prevalence. Further studies on enablers of IPV and the effect of conflict on IPV prevalence are needed to inform future interventions.

A prognostic model, including quantitative fetal fibronectin, to predict preterm labour: the QUIDS meta-analysis and prospective cohort study.

BACKGROUND: The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth. OBJECTIVES: To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness. DESIGN: The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an individual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin. DATA SOURCES/SETTING: The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres. PARTICIPANTS: Pregnant women at 22+0-34+6 weeks' gestation with signs and symptoms of preterm labour. HEALTH TECHNOLOGY BEING ASSESSED: Quantitative fetal fibronectin. MAIN OUTCOME MEASURES: Spontaneous preterm birth within 7 days. RESULTS: The individual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days. LIMITATIONS: The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation. CONCLUSIONS: A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour. FUTURE WORK: The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 52. See the NIHR Journals Library website for further project information.

Identifying which women with symptoms of labour will give birth early is challenging, so many women unnecessarily receive therapies aimed at preventing complications in preterm birth. A test called quantitative fetal fibronectin, which uses vaginal swab samples, may help to improve the diagnosis of preterm labour. Fetal fibronectin is a protein that is released from the fetal membranes that surround the developing baby in the womb. The lower the concentration of fetal fibronectin, the less likely the occurrence of preterm birth. Our aim was to see if quantitative fetal fibronectin, in combination with some features of pregnancy (e.g. previous pregnancy history and twin pregnancy), can accurately predict preterm birth in women who have symptoms of preterm labour. We asked women, their partners, doctors and midwives what information would be most useful to them, and how this should be presented. We then analysed previous research data; we used quantitative fetal fibronectin and clinical risk factors together to predict the chance of preterm birth. We explored which features could predict preterm birth most effectively while still being good value to the NHS. To ensure that this risk predictor worked in UK populations, we undertook a research study across 26 UK hospitals. Women who had symptoms of preterm labour were invited to participate. We collected information from these women (approximately 3000 women), including quantitative fetal fibronectin results. We found that a risk predictor comprising quantitative fetal fibronectin and four other features performed best at predicting whether or not preterm birth will occur within the next week for women with symptoms of preterm labour, and that this had potential to be clinically useful and cost-effective. The quantitative fetal fibronectin testing process was acceptable to women, and clinicians found the risk predictor useful. We used our findings to develop a risk calculator to help women and clinicians assess how likely preterm birth is, and decide whether or not to start treatment.

Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis.

BACKGROUND: Timely interventions in women presenting with preterm labour can substantially improve health outcomes for preterm babies. However, establishing such a diagnosis is very challenging, as signs and symptoms of preterm labour are common and can be nonspecific. We aimed to develop and externally validate a risk prediction model using concentration of vaginal fluid fetal fibronectin (quantitative fFN), in combination with clinical risk factors, for the prediction of spontaneous preterm birth and assessed its cost-effectiveness. METHODS AND FINDINGS: Pregnant women included in the analyses were 22+0 to 34+6 weeks gestation with signs and symptoms of preterm labour. The primary outcome was spontaneous preterm birth within 7 days of quantitative fFN test. The risk prediction model was developed and internally validated in an individual participant data (IPD) meta-analysis of 5 European prospective cohort studies (2009 to 2016; 1,783 women; mean age 29.7 years; median BMI 24.8 kg/m2; 67.6% White; 11.7% smokers; 51.8% nulliparous; 10.4% with multiple pregnancy; 139 [7.8%] with spontaneous preterm birth within 7 days). The model was then externally validated in a prospective cohort study in 26 United Kingdom centres (2016 to 2018; 2,924 women; mean age 28.2 years; median BMI 25.4 kg/m2; 88.2% White; 21% smokers; 35.2% nulliparous; 3.5% with multiple pregnancy; 85 [2.9%] with spontaneous preterm birth within 7 days). The developed risk prediction model for spontaneous preterm birth within 7 days included quantitative fFN, current smoking, not White ethnicity, nulliparity, and multiple pregnancy. After internal validation, the optimism adjusted area under the curve was 0.89 (95% CI 0.86 to 0.92), and the optimism adjusted Nagelkerke R2 was 35% (95% CI 33% to 37%). On external validation in the prospective UK cohort population, the area under the curve was 0.89 (95% CI 0.84 to 0.94), and Nagelkerke R2 of 36% (95% CI: 34% to 38%). Recalibration of the model's intercept was required to ensure overall calibration-in-the-large. A calibration curve suggested close agreement between predicted and observed risks in the range of predictions 0% to 10%, but some miscalibration (underprediction) at higher risks (slope 1.24 (95% CI 1.23 to 1.26)). Despite any miscalibration, the net benefit of the model was higher than "treat all" or "treat none" strategies for thresholds up to about 15% risk. The economic analysis found the prognostic model was cost effective, compared to using qualitative fFN, at a threshold for hospital admission and treatment of ≥2% risk of preterm birth within 7 days. Study limitations include the limited number of participants who are not White and levels of missing data for certain variables in the development dataset. CONCLUSIONS: In this study, we found that a risk prediction model including vaginal fFN concentration and clinical risk factors showed promising performance in the prediction of spontaneous preterm birth within 7 days of test and has potential to inform management decisions for women with threatened preterm labour. Further evaluation of the risk prediction model in clinical practice is required to determine whether the risk prediction model improves clinical outcomes if used in practice. TRIAL REGISTRATION: The study was approved by the West of Scotland Research Ethics Committee (16/WS/0068). The study was registered with ISRCTN Registry (ISRCTN 41598423) and NIHR Portfolio (CPMS: 31277).

Seroprevalence of human herpesvirus 8 in Ireland among blood donors, men who have sex with men, and heterosexual genitourinary medicine and infectious diseases clinic attendees.

Human herpesvirus 8 (HHV-8) seroprevalence varies geographically and between subpopulations. High seroprevalence rates have been ascribed to men who have sex with men (MSM), African migrants, and HIV-infected individuals. The objective of this study was to determine the seroprevalence of HHV-8 in an Irish population, including specific risk groups. A cross-sectional study of 200 blood donors and 200 genitourinary medicine (GUM) and infectious diseases (ID) clinic patients was performed, with testing for Immunoglobulin G (IgG) antibodies to HHV-8 lytic antigens using a commercial indirect fluorescence assay (Scimedx Corp.). Verification was performed at the Centers for Disease Control and Prevention (CDC). All 200 blood donor samples were negative for HHV-8 IgG antibodies. 21% of GUM and ID patients were positive for HHV-8 IgG antibodies. One hundred of these patients were MSM, 35% of whom were HHV-8 seropositive (46% of HIV-positive MSM and 24% of HIV-negative MSM). Of 100 heterosexual patients, only 7% were HHV-8 seropositive. The absence of seropositivity in 200 Irish blood donors may suggest that Ireland has a low overall population HHV-8 seroprevalence. The proportion of HHV-8 seropositivity in the MSM population was significantly higher than in the heterosexual population and most marked in HIV-positive MSM.

Refractory depression - mechanisms and efficacy of radically open dialectical behaviour therapy (RefraMED): findings of a randomised trial on benefits and harms.

BACKGROUND: Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression. AIMS: To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627). METHOD: RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated. RESULTS: After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94-9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI -2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI -2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group. CONCLUSIONS: The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.

Intimate partner violence in pregnancy: a cross-sectional study from post-conflict northern Uganda.

OBJECTIVES: To determine the prevalence of intimate partner violence (IPV) in pregnancy and to understand associations and determinants. DESIGN: Cross-sectional survey. SETTING: Two rural health clinics in post-conflict northern Uganda. PARTICIPANTS: Women attending two rural health clinics for a new service providing cervical cancer screening, who had experienced pregnancy. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected by a questionnaire using validated questions from the demographic health survey women's questionnaire and the domestic violence module. Data were entered into tablets using Questionnaire Development System software. Bivariate and multivariate logistic regression was performed, using experience of IPV in pregnancy as the dependent variable. SPSS V.25 was used for all analysis. RESULTS: Of 409 participant women, 26.7% (95% CI 18.6% to 35.9%) reported having been slapped, hit or beaten by a partner while pregnant. For 32.3% (95% CI 20.2% to 37.9%) of the women the violence became worse during pregnancy. Women who had ever experienced IPV in pregnancy were more likely to have experienced violence in the previous 12 months (OR 4.45, 95% CI 2.80 to 7.09). In multivariate logistic regression, the strongest independent associations with IPV in pregnancy were partner's daily drinking of alcohol (OR 2.02, 95% CI 1.19 to 3.43) and controlling behaviours (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSIONS: The women in this study had more exposure to IPV in pregnancy than previously reported for this region. Women's previous experience of intimate partner violence, partner's daily use of alcohol and his controlling behaviours were strong associations with IPV in pregnancy. This study highlights the uneven distribution of risk and the importance of research among the most vulnerable population in rural and disadvantaged settings. More research is needed in local rural and urban settings to illuminate this result and inform intervention and policy.

Prevalence and correlates of intimate partner violence against women in conflict affected northern Uganda: a cross-sectional study.

BACKGROUND: Intimate partner violence (IPV) is an important public health issue as it impacts negatively on health, economic and development outcomes. In conflict affected northern Uganda, IPV prevalence is high and additional context-specific risk factors exist. People residing in this region have been displaced, exposed to war and violence, and had livelihoods destroyed. There are few studies examining IPV in this setting. In this study we aim to further understand the prevalence of IPV towards women and its associations in conflict affected northern Uganda. METHODS: This was a cross-sectional, behavioural survey designed to capture quantitative information related to experiences of IPV among women living near two health clinics in rural northern Uganda. There were 409 women who participated in the survey. Data were analysed using logistic regression. RESULTS: High rates of emotional, physical and sexual IPV were found; 78.5% of women had experienced at least one type of IPV, and slightly more than half of the participants had experienced IPV in the 12 months prior to the survey. Many women felt that IPV was justified in certain situations. Significant determinants of IPV included alcohol abuse by the male partner (OR 2.22, 95% CI 1.34-3.73); partner having been in a physical fight with another man (OR 1.90, 95% CI 1.12-3.23); controlling behaviours by the male partner (OR 1.21, CI 1.08-1.36). and younger age of the woman (OR 0.95, 95% CI 0.92-0.98). Educational level was not independently associated with IPV. CONCLUSIONS: Our findings show that IPV is a significant issue in conflict affected northern Uganda, and attitudes that normalise and justify IPV are common. Alcohol abuse among young men in northern Uganda is highly prevalent and strongly associated with IPV towards women, as are controlling behaviours exhibited by the male partner. Interventions to reduce alcohol consumption among men in this region are likely to have important benefits in reducing the prevalence of IPV, and attitudes and behaviours that support IPV need to be further understood and addressed. Many women in conflict affected northern Uganda likely have additional risk factors for IPV related to previous exposure to war violence, however this was not directly measured in the present study. Further research into IPV in northern Uganda, and its relationship to exposure to conflict, is greatly needed.

Refractory depression - cost-effectiveness of radically open dialectical behaviour therapy: findings of economic evaluation of RefraMED trial.

BACKGROUND: Refractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.AimsTo estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627). METHOD: We undertook a cost-effectiveness analysis alongside a randomised trial evaluating RO DBT plus TAU versus TAU alone for refractory depression in three UK secondary care centres. Our economic evaluation, 12 months after randomisation, adopted the perspective of the UK National Health Service (NHS) and personal social services. It evaluated cost-effectiveness by comparing the net cost of RO DBT with the net gain in quality-adjusted life-years (QALYs), estimated using the EQ-5D-3L measure of health-related quality of life. RESULTS: The additional cost of RO DBT plus TAU compared with TAU alone was £7048 and was associated with a difference of 0.032 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of £220 250 per QALY. This ICER was well above the National Institute for Health and Care Excellence (NICE) upper threshold of £30 000 per QALY. A cost-effectiveness acceptability curve indicated that RO DBT had a zero probability of being cost-effective compared with TAU at the NICE £30 000 threshold. CONCLUSIONS: In its current resource-intensive form, RO DBT is not a cost-effective use of resources in the UK NHS.Declaration of interestR.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from the National Institute for Health Research (NIHR). T.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd, and a grant outside the submitted work from the Medical Research Council. He was co-director of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two directors of Radically Open Ltd. H.O'M. reports personal fees outside the submitted work from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.R. provides RO DBT supervision through her company S C Rushbrook Ltd. I.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M. Stanton reports personal fees outside the submitted work from British Isles DBT Training, Stanton Psychological Services Ltd and Taylor & Francis. M. Swales reports personal fees outside the submitted work from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis. B.W. was co-director of Radically Open Ltd between November 2014 and February 2015.

Effect of a participatory intervention in women's self-help groups for the prevention of chronic suppurative otitis media in their children in Jumla Nepal: a cluster-randomised trial.

BACKGROUND: Chronic suppurative otitis media (CSOM) causes preventable deafness and disproportionately affects children living in poverty. Our hypothesis was that health promotion in women's groups would increase their knowledge, attitudes and practices (KAP) regarding ear disease and reduce the prevalence of CSOM in their children. METHODS: We did a cluster randomised trial in two village development committees (VDCs) in Jumla, Nepal. In July 2014, 30 women's groups were randomly allocated to intervention or control, stratified by VDC and distance to the road. The intervention groups participated in three sessions of health promotion using the WHO Hearing and Ear Care Training Resource Basic Level. The primary outcome was women's KAP score and the secondary outcome was prevalence of CSOM in their children at 12 month follow-up. Analyses were by intention to treat. Participants and the research team were not masked to allocation. RESULTS: In June and July 2014 we recruited 508 women and 937 of their children. 12 months later there was no difference in the women's KAP score (mean difference 0.14, 95% CI - 0.1 to 0.38, P = 0.25) or the prevalence of CSOM in their children (OR 1.10, 95%CI 0.62 to 1.84, P = 0.75) between intervention and control groups. However, overall, there was a significant improvement in the KAP score (mean difference - 0.51, 95% CI - 0.71,to - 0.31, P < 0.0001) and in the prevalence of CSOM from baseline 11.2% to follow-up 7.1% (P < 0.0001). CONCLUSIONS: Health promotion in women's groups did not improve maternal KAP or reduce prevalence of CSOM. Over time there was a significant improvement in women's KAP score and reduction in the prevalence of CSOM which may be attributable to our presence in the community offering treatment to affected children, talking to their parents and providing ciprofloxacin drops to the local health posts. More research is needed in low resource settings to test our findings. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry 12,614,000,231,640 ; Date of registration: 5.3.2014: Prospectively registered.

The Osteogenic Potential of Brown Seaweed Extracts.

Marine drugs hold significantly more promise than their terrestrial counterparts, which could help to solve the current shortfall in treatments for osteoporosis and other bone related diseases. Fucoxanthin is the main carotenoid found in brown seaweed, and has many perceived health benefits, including potential bone therapeutic properties. This study assessed the osteogenic potential of pure fucoxanthin and crude extracts containing both fucoxanthin and phenolic fractions (also cited to have osteogenic potential) isolated from two intertidal species of brown seaweed, Laminaria digitata and Ascophyllum nodosum. In vitro studies were performed using a human foetal osteoblast cell line (hFOBs) and primary human bone marrow stromal cells (hBMSCs). The results found pure fucoxanthin inhibitory to cell proliferation in hFOBs at higher concentrations, whereas, the crude extracts containing both polyphenols and fucoxanthin showed the ability to scavenge free radicals, which masked this effect. None of the extracts tested showed strong pro-osteogenic effects in either cell type tested, failing to support previously reported positive effects.

The Impact of an Electronic Patient Bedside Observation and Handover System on Clinical Practice: Mixed-Methods Evaluation.

BACKGROUND: Patient safety literature has long reported the need for early recognition of deteriorating patients. Early warning scores (EWSs) are commonly implemented as "track and trigger," or rapid response systems for monitoring and early recognition of acute patient deterioration. This study presents a human factors evaluation of a hospital-wide transformation in practice, engendered by the deployment of an innovative electronic observations (eObs) and handover system. This technology enables real-time information processing at the patient's bedside, improves visibility of patient data, and streamlines communication within clinical teams. OBJECTIVE: The aim of this study was to identify improvement and deterioration in workplace efficiency and quality of care resulting from the large-scale imposition of new technology. METHODS: A total of 85 hours of direct structured observations of clinical staff were carried out before and after deployment. We conducted 40 interviews with a range of clinicians. A longitudinal analysis of critical care audit and electronically recorded patient safety incident reports was conducted. The study was undertaken in a large secondary-care facility in the United Kingdom. RESULTS: Roll-out of eObs was associated with approximately 10% reduction in total unplanned admissions to critical care units from eObs-equipped wards. Over time, staff appropriated the technology as a tool for communication, workload management, and improving awareness of team capacity. A negative factor was perceived as lack of engagement with the system by senior clinicians. Doctors spent less time in the office (68.7% to 25.6%). More time was spent at the nurses' station (6.6% to 41.7%). Patient contact time was more than doubled (2.9% to 7.3%). CONCLUSIONS: Since deployment, clinicians have more time for patient care because of reduced time spent inputting and accessing data. The formation of a specialist clinical team to lead the roll-out was universally lauded as the reason for success. Staff valued the technology as a tool for managing workload and identified improved situational awareness as a key benefit. For future technology deployments, the staff requested more training preroll-out, in addition to engagement and support from senior clinicians.

Prevalence, Macrolide Resistance, and Fluoroquinolone Resistance in Mycoplasma genitalium in Men Who Have Sex With Men Attending an Sexually Transmitted Disease Clinic in Dublin, Ireland in 2017-2018.

This is the first prevalence study of Mycoplasma genitalium and antimicrobial resistance study in Ireland. In urine samples from men who have sex with men (n = 400) attending a sexually transmitted disease clinic in Dublin, the prevalence of M. genitalium was 3% (12 of 400 specimens; 95% confidence interval, 1.3-4.7%), and the prevalences of macrolide resistance (75%), fluoroquinolone resistance (33.3%), and multidrug resistance (33.3%) were very high.

Chasing the rainbow: pleasure, sex-based sociality and consumerism in navigating and exiting the Irish Chemsex scene.

Club drug use among gay, bisexual and other men who have sex with men is increasingly normalised within sexual contexts and is associated with increased sexual risk behaviours. The term Chemsex is used to describe sexualised drug use lasting several hours or days with multiple sexual partners. A small pilot study, underpinned by interpretative phenomenological analysis (IPA), was conducted in Dublin, Ireland. Interviews were conducted with 10 men who were experiencing physical and emotional health problems as a consequence of their participation in sexualised drug use and wished to exit the Chemsex scene. Interviews explored experiences of sexualised drug use, motives to partake, the organisation of Chemsex parties and group connectivity, drugs used, harm reduction, pleasure and consequences of participation over time. Four basic themes emerged from the analysis: social and cyber arrangements within the Dublin Chemsex scene; poly drug use and experiences of drug dependence; drug and sexual harm reduction within the Chemsex circle of novices and experts; and sexualised drug use, escapism and compulsive participation. Two higher-order themes were also apparent: first, the reinforcing aspects of drug and sexual pleasure; and second, the interplay between excess drug consumption and sex, and drug dependence.

Correction: Screening for osteogenic activity in extracts from Irish marine organisms: The potential of Ceramium pallidum.

[This corrects the article DOI: 10.1371/journal.pone.0207303.].