Does domiciliary welfare rights advice improve health-related quality of life in independent-living, socio-economically disadvantaged people aged ≥60 years? Randomised controlled trial, economic and process evaluations in the North East of England.

BACKGROUND: There are major socio-economic gradients in health that could be influenced by increasing personal resources. Welfare rights advice can enhance resources but has not been rigorously evaluated for health-related impacts. METHODS: Randomised, wait-list controlled trial with individual allocation, stratified by general practice, of welfare rights advice and assistance with benefit entitlements, delivered in participants' homes by trained advisors. Control was usual care. Participants were volunteers sampled from among all those aged ≥60 years registered with general practices in socio-economically deprived areas of north east England. Outcomes at 24 months were: CASP-19 score (primary), a measure of health-related quality of life; changes in income, social and physical function, and cost-effectiveness (secondary). Intention to treat analysis compared outcomes using multiple regression, with adjustment for stratification and key covariates. Qualitative interviews with purposive samples from both trial arms were thematically analysed. FINDINGS: Of 3912 individuals approached, 755 consented and were randomised (381 Intervention, 374 Control). Results refer to outcomes at 24 months, with data available on 562 (74.4%) participants. Intervention was received as intended by 335 (88%), with 84 (22%) awarded additional benefit entitlements; 46 did not receive any welfare rights advice, and none of these were awarded additional benefits. Mean CASP-19 scores were 42.9 (Intervention) and 42.4 (Control) (adjusted mean difference 0.3 [95%CI -0.8, 1.5]). There were no significant differences in secondary outcomes except Intervention participants reported receiving more care at home at 24m (53.7 (Intervention) vs 42.0 (Control) hours/week (adjusted mean difference 26.3 [95%CIs 0.8, 56.1]). Exploratory analyses did not support an intervention effect and economic evaluation suggested the intervention was unlikely to be cost-effective. Qualitative data from 50 interviews suggested there were improvements in quality of life among those receiving additional benefits. CONCLUSIONS: We found no effects on health outcomes; fewer participants than anticipated received additional benefit entitlements, and participants were more affluent than expected. Our findings do not support delivery of domiciliary welfare rights advice to achieve the health outcomes assessed in this population. However, better intervention targeting may reveal worthwhile health impacts.All authors received a grant of £798,884 from the UK National Institute of Health Research, Public Health Research Programme (No. 09/3009/ 02). www.nihr.ac.uk. All authors received a grant of £28,000 from the North East Strategic Health Authority in 2012 to cover the costs of delivering the intervention, associated training and other nonresearch costs of this study. North East SHA no longer exists. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The association between parity, infant gender, higher level of paternal education and preterm birth in Pakistan: a cohort study

<p>Abstract</p> <p>Background</p> <p>High rates of antenatal depression and preterm birth have been reported in Pakistan. Self reported maternal stress and depression have been associated with preterm birth; however findings are inconsistent. Cortisol is a biological marker of stress and depression, and its measurement may assist in understanding the influence of self reported maternal stress and depression on preterm birth.</p> <p>Methods</p> <p>In a prospective cohort study pregnant women between 28 to 30 weeks of gestation from the Aga Khan Hospital for Women and Children completed the A-Z Stress Scale and the Centre for Epidemiology Studies Depression Scale to assess stress and depression respectively, and had a blood cortisol level drawn. Women were followed up after delivery to determine birth outcomes. Correlation coefficients and Wilcoxon rank sum test was used to assess relationship between preterm birth, stress, depression and cortisol. Logistic regression analysis was used to determine the key factors predictive of preterm birth.</p> <p>Results</p> <p>132 pregnant women participated of whom 125 pregnant women had both questionnaire and cortisol level data and an additional seven had questionnaire data only. Almost 20% of pregnant women (19·7%, 95% CI 13·3-27·5) experienced a high level of stress and nearly twice as many (40·9%, 95% CI 32·4-49·8%) experienced depressive symptoms. The median of cortisol level was 27·40 ug/dl (IQR 22·5-34·2). The preterm birth rate was 11·4% (95% CI 6·5-18). There was no relationship between cortisol values and stress scale or depression. There was a significant positive relationship between maternal depression and stress. Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. Insufficient numbers of preterm births were available to warrant the development of a multivariable logistic regression model.</p> <p>Conclusions</p> <p>Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. There was no relationship between stress, and depression, cortisol and preterm birth. There were high rates of stress and depression among this sample suggesting that there are missed opportunities to address mental health needs in the prenatal period. Improved methods of measurement are required to better understand the psychobiological basis of preterm birth.</p

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

Link workers’ perspectives on factors enabling and preventing client engagement with social prescribing

For a social prescribing intervention to achieve its aims, clients must first be effectively engaged. A ‘link worker’ facilitating linkage between clients and community resources has been identified as a vital component of social prescribing. However, the mechanisms underpinning successful linkage remain underspecified. This qualitative study is the first to explore link workers’ own definitions of their role in social prescribing and the skills and qualities identified by link workers themselves as necessary for effective client linkage. This study also explores ‘threats’ to successful linked social prescribing and the challenges link workers face in carrying out their work. Link workers in a social prescribing scheme in a socioeconomically deprived area of North East England were interviewed in two phases between June 2015 and August 2016. The first phase comprised five focus groups (n = 15) and individual semi‐structured interviews (n = 15) conducted with each focus group participant. The follow‐up phase comprised four focus groups (n = 15). Thematic data analysis highlighted the importance of providing a holistic service focusing on the wider social determinants of health. Enabling client engagement required ‘well‐networked’ link workers with the time and the personal skills required to develop a trusting relationship with clients while maintaining professional boundaries by fostering empowerment rather than dependency. Challenges to client engagement included: variation in the volume and suitability of primary‐care referrals; difficulties balancing quality of intervention provision and meeting referral targets; and link workers’ training inadequately preparing them for their complex and demanding role. At a broader level, public sector cuts negatively impacted upon link workers’ ability to refer patients into suitable services due to unacceptably long waiting lists or service cutbacks. This study demonstrates that enabling client engagement in social prescribing requires skilled link workers supported by healthcare referrer ‘buy‐in’ and with access to training tailored to what is a complex and demanding role

Link Worker social prescribing to improve health and well-being for people with long-term conditions: qualitative study of service user perceptions

Objectives To describe the experiences of patients with long-term conditions who are referred to and engage with a Link Worker social prescribing programme and identify the impact of the Link Worker programme on health and well-being. Design Qualitative study using semistructured interviews with thematic analysis of the data. Intervention Link Worker social prescribing programme comprising personalised support to identify meaningful health and wellness goals, ongoing support to achieve agreed objectives and linkage into appropriate community services. Setting Inner-city area in West Newcastle upon Tyne, UK (population n=132 000) ranked 40th most socioeconomically deprived in England, served by 17 general practices. Participants Thirty adults with long-term conditions, 14 female, 16 male aged 40-74 years, mean age 62 years, 24 white British, 1 white Irish, 5 from black and minority ethnic communities. Results Most participants experienced multimorbidity combined with mental health problems, low self-confidence and social isolation. All were adversely affected physically, emotionally and socially by their health problems. The intervention engendered feelings of control and self-confidence, reduced social isolation and had a positive impact on health-related behaviours including weight loss, healthier eating and increased physical activity. Management of long-term conditions and mental health in the face of multimorbidity improved and participants reported greater resilience and more effective problem-solving strategies. Conclusions Findings suggest that tackling complex and long-term health problems requires an extensive holistic approach not possible in routine primary care. This model of social prescribing, which takes into account physical and mental health, and social and economic issues, was successful for patients who engaged with the service. Future research on a larger scale is required to assess when and for whom social prescribing is clinically effective and cost-effective

Service-users’ perspectives of link worker social prescribing: a qualitative follow-up study

Background: Social prescribing enables health-care professionals to address non-medical causes of ill-health by harnessing the resources of the voluntary and community sectors in patient care. Although increasingly popular in the UK, evidence for the effectiveness of social prescribing is inconclusive and longer-term studies are needed. This study aimed to explore experiences of social prescribing among people with long-term conditions one to two years after their initial engagement with a social prescribing service. Methods: Qualitative methods comprising semi-structured follow-up interviews were conducted with 24 users of a link worker social prescribing service who had participated in an earlier study. Participants were aged between 40 and 74 years and were living in a socioeconomically-deprived area of North East England. Results: Participants reported reduced social isolation and improvements in their condition management and health-related behaviours. However, many participants had experienced setbacks, requiring continued support to overcome problems due to multi-morbidity, family circumstances and social, economic or cultural factors. Findings indicated that, in this sample of people facing complex health and socioeconomic issues, longer-term intervention and support was required. Features of the link worker social prescribing intervention that were positively appraised by participants, included a highly personalised service to reflect individual goal setting priorities and a focus on gradual and holistic change dealing with issues beyond health. The important role of a strong and supportive relationship with an easily-accessible link worker in promoting sustained behaviour change highlights the importance of link worker continuity. A lack of suitable and accessible voluntary and community services for onward referral acted as a barrier to involvement for some participants. Conclusions: This study highlights issues of interest to commissioners and providers of social prescribing. Engagement with social prescribing for up to two years was examined and continued involvement was identified for those with complex issues, suggesting that a long-term intervention is required. The availability of onward referral services is an important consideration for social prescribing in a time of constrained public spending. From a research perspective, the range of improvements and their episodic nature suggest that the evaluation of social prescribing interventions requires both quantitative and qualitative data collected longitudinally

Spatial variation in parasite abundance: evidence of geographical population structuring in southern garfish Hyporhamphus melanochir

Southern garfish Hyporhamphus melanochir were examined for metazoan parasites from nine sites in three regions (Spencer Gulf, Gulf St Vincent and northern Kangaroo Island) in South Australia to document parasite assemblages, identify candidate species suitable for use as biological tags and investigate spatial variation in parasite abundance. Four ectoparasite and 10 endoparasite species were identified representing Cestoda, Trematoda, Monogenea, Nematoda, Acanthocephala, Copepoda and Isopoda. Lernaeenicus hemirhamphi, Micracanthorhynchina hemirhamphi, Mothocya halei and Philometra sp. were suggested for 'permanent' biological markers. Multivariate discriminant function analysis showed that most sites could be distinguished based on differences in parasite abundance. Four endoparasites (Conohelmins sp., Hysterothylacium sp., M. hemirhamphi and Philometra sp.) were most important for site characterization. Limited spatial variation in permanent endoparasite abundance among localities in northern Spencer Gulf provided evidence for a distinct northern Spencer Gulf population with little interregional mixing. In contrast, considerable spatial variation in permanent endoparasite abundance between localities sampled off Kangaroo Island implied limited local movement and suggested H. melanochir may comprise a metapopulation structure. These results largely align with recent evidence from otolith chemistry that indicates fine-scale geographical population structuring in South Australian waters.K. S. Hutson, E. L. Brock and M. A. Stee

Randomised controlled trial with economic and process evaluations of domiciliary welfare rights advice for socioeconomically disadvantaged older people recruited via primary health care (the Do-Well study)

Background Welfare rights advice services are effective at maximising previously unclaimed welfare benefits, but their impact on health has not been evaluated. Objective To establish the acceptability, cost-effectiveness and effect on health of a domiciliary welfare rights advice service targeting older people, compared with usual practice. Design A pragmatic, individually randomised, parallel-group, single-blinded, wait-list controlled trial, with economic and process evaluations. Data were collected by interview at baseline and 24 months, and by self-completion questionnaire at 12 months. Qualitative interviews were undertaken with purposive samples of 50 trial participants and 17 professionals to explore the intervention’s acceptability and its perceived impacts. Setting Participants’ homes in North East England, UK. Participants A total of 755 volunteers aged ≥ 60 years, living in their own homes, fluent in English and not terminally ill, recruited from the registers of 17 general practices with an Index of Multiple Deprivation within the most deprived two-fifths of the distribution for England, and with no previous access to welfare rights advice services. Interventions Welfare rights advice, comprising face-to-face consultations, active assistance with benefit claims and follow-up as required until no longer needed, delivered in participants’ own homes by a qualified welfare rights advisor. Control group participants received usual care until the 24-month follow-up, after which they received the intervention. Main outcome measures The primary outcome was health-related quality of life (HRQoL), assessed using the CASP-19 (Control, Autonomy, Self-realisation and Pleasure) score. The secondary outcomes included general health status, health behaviours, independence and hours per week of care, mortality and changes in financial status. Results A total of 755 out of 3912 (19%) general practice patients agreed to participate and were randomised (intervention, n = 381; control, n = 374). In the intervention group, 335 participants (88%) received the intervention. A total of 605 (80%) participants completed the 12-month follow-up and 562 (75%) completed the 24-month follow-up. Only 84 (22%) intervention group participants were awarded additional benefits. There was no significant difference in CASP-19 score between the intervention and control groups at 24 months [adjusted mean difference 0.3, 95% confidence interval (CI) –0.8 to 1.5], but a significant increase in hours of home care per week in the intervention group (adjusted difference 26.3 hours/week, 95% CI 0.8 to 56.1 hours/week). Exploratory analyses found a weak positive correlation between CASP-19 score and the amount of time since receipt of the benefit (0.39, 95% CI 0.16 to 0.58). The qualitative data suggest that the intervention was acceptable and that receipt of additional benefits was perceived by participants and professionals as having had a positive impact on health and quality of life. The mean cost was £44 per participant, the incremental mean health gain was 0.009 quality-adjusted life-years (QALYs) (95% CI –0.038 to 0.055 QALYs) and the incremental cost-effectiveness ratio was £1914 per QALY gained. Conclusions The trial did not provide sufficient evidence to support domiciliary welfare rights advice as a means of promoting health among older people, but it yielded qualitative findings that suggest important impacts on HRQoL. The intervention needs to be better targeted to those most likely to benefit. Future work Further follow-up of the trial could identify whether or not outcomes diverge among intervention and control groups over time. Research is needed to better understand how to target welfare rights advice to those most in need