Patient pathways for rare diseases in Europe: ataxia as an example.

BACKGROUND: Progressive ataxias are rare and complex neurological disorders that represent a challenge for the clinicians to diagnose and manage them. This study explored the patient pathways of individuals attending specialist ataxia centres (SAC) compared with non-specialist settings. We investigated specifically how diagnosis was reached, the access to healthcare services, treatments, and care satisfaction. The focus of this study was on early intervention, coordination of treatment to understand the care provision in different countries. METHODS: A patient survey was done in the UK, Germany and Italy to gather information about diagnosis and management of the ataxias in specialist (SAC) and non-specialist settings, utilisation of other primary and secondary health care services, and patients' satisfaction of received treatment. RESULTS: Patients gave positive feedback about the role of SAC in understanding their condition, ways to manage their ataxia (p < 0.001; UK) and delivering care adapted to their needs (p < 0.001; UK), in coordinating referrals to other healthcare specialists, and in offering opportunities to take part in research studies. Similar barriers for patients were identified in accessing the SACs among the selected countries, UK, Germany, and Italy. CONCLUSIONS: This study provides crucial information about the ataxia patients care pathways in three European countries. Overall, the results showed a trend in patients' satisfaction being better in SAC compared to non-SAC. The outcomes can be used now for policy recommendations on how to improve treatment and care for people with these very rare and complex neurological diseases across Europe.

Thermoregulation, Not Just Camouflage: The Unique Vasculature of Giraffe Patches. A Cadaver Study with Clinical Implications.

BACKGROUND: Serendipitously, a dead giraffe provided opportunity to study its vascular anatomy. Comparative animal studies have revealed important information for designing new flaps and new microsurgical techniques. So, do giraffe's patches support a thermal window concept, do animals with similar markings and habitat have a similar thermoregulatory role, and could results offer new insight into human thermoregulation and free tissue transfer? METHODS: Previously described lead-oxide arterial-only injection studies, of a single giraffe, zebra, Africa wild dog, and spotted jaguar, all with wire-encircled pigmented patches; and archival human, pig, dog, cat, and rabbit studies, were compared. RESULTS: Each giraffe patch was supplied by just a single artery (angiosome) averaging 0.9 mm diameter, that divided near its center and sent dense, long, parallel, radiating spoke-wheel branches averaging 0.62 mm diameter to the patch margin, continuing as reduced-caliber choke anastomoses averaging 0.8 mm to link adjacent patch angiosomes. Uniquely arranged large veins, with an average of 1.66 mm, encircled the patches in the pale skin paralleled by arteriae comitantes averaging 0.22 mm. These arteries, connected to patch angiosomes, filled the veins intermittently by means of arteriovenous (A-V) shunts averaging 0.12 mm in diameter of magnitude never seen before in any species studied. None of the other three animals had angiosome territories matching their pigmented fur, or significant A-V filling. CONCLUSIONS: This study supports the "thermostatic" concept of the giraffe skin patches, with A-V shunts playing a major role. It affirms the need for further studies of these shunts in human thermoregulation and other flow regulations in physiology, pathology, and free tissue transfer.

The Positive Choices trial: update to study protocol for a phase-III RCT trial of a whole-school social-marketing intervention to promote sexual health and reduce health inequalities.

BACKGROUND: Positive Choices is a whole-school social-marketing intervention to promote sexual health among secondary school students. Intervention comprises the following: school health promotion council involving staff and students coordinating delivery, student survey to inform local tailoring, teacher-delivered classroom curriculum, student-run campaigns, parent information and review of sexual/reproductive health services to inform improvements. This trial builds on an optimisation/pilot-RCT study which met progression criteria, plus findings from another pilot RCT of the Project Respect school-based intervention to prevent dating and relationship violence which concluded such work should be integrated within Positive Choices. Young people carry a disproportionate burden of adverse sexual health; most do not report competence at first sex. Relationships and sex education in schools can contribute to promoting sexual health but effects are small, inconsistent and not sustained. Such work needs to be supplemented by 'whole-school' (e.g. student campaigns, sexual health services) and 'social marketing' (harnessing commercial marketing to social ends) approaches for which there is good review-level evidence but not from the UK. METHODS: We will conduct a cluster RCT across 50 schools (minimum 6440, maximum 8500 students) allocated 1:1 to intervention/control assessing outcomes at 33 months. Our primary outcome is non-competent first sex. Secondary outcomes are non-competent last sex, age at sexual debut, non-use of contraception at first and last sex among those reporting heterosexual intercourse, number of sexual partners, dating and relationship violence, sexually transmitted infections and pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys. We will recruit 50 school and undertake baseline surveys by March 2022, implement the intervention over the 2022-2024 school years and conduct the economic and process evaluations by July 2024; undertake follow-up surveys by December 2024; complete analyses, all patient and policy involvement and draft the study report by March 2025 and engage in knowledge exchange from December 2024. DISCUSSION: This trial is one of a growing number focused on whole-school approaches to public health in schools. The key scientific output will be evidence about the effectiveness, costs and potential scalability and transferability of Positive Choices. TRIAL REGISTRATION: ISRCTN No: ISRCTN16723909 . Registered on 3 September 2021.

The impact of remote home monitoring of people with COVID-19 using pulse oximetry: A national population and observational study.

BACKGROUND: Remote home monitoring of people testing positive for COVID-19 using pulse oximetry was implemented across England during the Winter of 2020/21 to identify falling blood oxygen saturation levels at an early stage. This was hypothesised to enable earlier hospital admission, reduce the need for intensive care and improve survival. This study is an evaluation of the clinical effectiveness of the pre-hospital monitoring programme, COVID oximetry @home (CO@h). METHODS: The setting was all Clinical Commissioning Group (CCG) areas in England where there were complete data on the number of people enrolled onto the programme between 2nd November 2020 and 21st February 2021. We analysed relationships at a geographical area level between the extent to which people aged 65 or over were enrolled onto the programme and outcomes over the period between November 2020 to February 2021. FINDINGS: For every 10% increase in coverage of the programme, mortality was reduced by 2% (95% confidence interval:4% reduction to 1% increase), admissions increased by 3% (-1% to 7%), in-hospital mortality fell by 3% (-8% to 3%) and lengths of stay increased by 1·8% (-1·2% to 4·9%). None of these results are statistically significant, although the confidence interval indicates that any adverse effect on mortality would be small, but a mortality reduction of up to 4% may have resulted from the programme. INTERPRETATION: There are several possible explanations for our findings. One is that CO@h did not have the hypothesised impact. Another is that the low rates of enrolment and incomplete data in many areas reduced the chances of detecting any impact that may have existed. Also, CO@h has been implemented in many different ways across the country and these may have had varying levels of effect. FUNDING: This is independent research funded by the National Institute for Health Research, Health Services & Delivery Research programme (RSET Project no. 16/138/17; BRACE Project no. 16/138/31) and NHSEI. NJF is an NIHR Senior Investigator.

Effectiveness of Enhanced Performance Feedback on Appropriate Use of Blood Transfusions: A Comparison of 2 Cluster Randomized Trials.

Importance: Auditing and feedback are frequently used to improve patient care. However, it remains unclear how to optimize feedback effectiveness for the appropriate use of treatments such as blood transfusion, a common but costly procedure that is more often overused than underused. Objective: To evaluate 2 theoretically informed feedback interventions to improve the appropriate use of blood transfusions. Design, Setting, and Participants: Two sequential, linked 2 × 2 cluster randomized trials were performed in hospitals in the UK participating in national audits of transfusion for perioperative anemia and management of hematological disorders. Data were collected for a surgical trial from October 1, 2014, to October 31, 2016, with follow-up completed on October 31, 2016. Data were collected for a hematological trial through follow-up from July 1, 2015, to June 30, 2017. Trial data were analyzed from November 1, 2016, to June 1, 2019. Interventions: Hospitals were randomized to standard content or enhanced content to improve feedback clarity and usability and to standard support or enhanced support for staff to act on feedback. Main Outcomes and Measures: The primary end point was appropriateness of transfusions audited at 12 months. Secondary end points included volume of transfusions (aiming for reductions at patient and cluster levels) and transfusion-related adverse events and reactions. Results: One hundred thirty-five of 152 eligible clusters participated in the surgical audit (2714 patients; mean [SD] age, 74.9 [14.0] years; 1809 women [66.7%]), and 134 of 141 participated in the hematological audit (4439 patients; median age, 72.0 [IQR, 64.0-80.0] years; 2641 men [59.5%]). Fifty-seven of 69 clusters (82.6%) in the surgical audit randomized to enhanced content downloaded reports compared with 52 of 66 clusters (78.8%) randomized to standard reports. Fifty-nine of 68 clusters (86.8%) randomized to enhanced support logged onto the toolkit. The proportion of patients with appropriate transfusions was 0.184 for standard content and 0.176 for enhanced content (adjusted odds ratio [OR], 0.91 [97.5% CI, 0.61-1.36]) and 0.181 for standard support and 0.180 for enhanced support (adjusted OR, 1.05 [97.5% CI, 0.68-1.61]). For the hematological audit, 53 of 66 clusters (80.3%) randomized to enhanced content downloaded the reports compared with 53 of 68 clusters (77.9%) randomized to standard content. Forty-nine of 67 clusters sites (73.1%) assigned to enhanced support logged into the toolkit at least once. The proportion of patients with appropriate transfusions was 0.744 for standard content and 0.714 for enhanced content (adjusted OR, 0.81 [97.5% CI, 0.56-1.12]), and 0.739 for standard support and 0.721 for enhanced support (adjusted OR, 0.96 [97.5% CI, 0.67-1.38]). Conclusions and Relevance: This comparison of cluster randomized trials found that interventions to improve feedback usability and guide local action were no more effective than standard feedback in increasing the appropriate use of blood transfusions. Auditing and feedback delivered at scale is a complex and costly program; therefore, effective responses may depend on developing robust local quality improvement arrangements, which can be evaluated using rigorous experimental designs embedded within national programs. Trial Registration: isrctn.org Identifier: ISRCTN15490813.

Achieving Quality and Effectiveness in Dementia Using Crisis Teams (AQUEDUCT): a study protocol for a randomised controlled trial of a Resource Kit.

BACKGROUND: Improving care at home for people with dementia is a core policy goal in the dementia strategies of many European countries. A challenge to effective home support is the occurrence of crises in the care of people with dementia which arise from changes in their health and social circumstances. Improving the management of these crises may prevent hospital admissions and facilitate better and longer care at home. This trial is part of a National Institute for Health Research funded programme, AQUEDUCT, which aims to improve the quality and effectiveness of teams working to manage crises in dementia. METHODS/DESIGN: It is a pragmatic randomised controlled trial of an online Resource Kit to enhance practice in teams managing crises in dementia care. Thirty teams managing mental health crises in dementia in community settings will be randomised between the Resource Kit intervention and treatment as usual. The primary outcome measure is psychiatric admissions to hospital for people with dementia in the teams' catchment area recorded 6 months after randomisation. Other outcomes include quality of life measures for people with dementia and their carers, practitioner impact measures, acute hospital admissions and costs. To enhance understanding of the Resource Kit intervention, qualitative work will explore staff, patient and carers' experience. DISCUSSION: The Resource Kit intervention reflects current policy to enable home-based care for people with dementia by addressing the management of crises which threaten the viability of care at home. It is based upon a model of best practice for managing crises in dementia designed to enhance the quality of care, developed in partnership with people with dementia, carers and practitioners. If the Resource Kit is shown to be clinically and cost-effective in this study, this will enhance the probability of its incorporation into mainstream practice. TRIAL REGISTRATION: ISRCTN 42855694 ; Registered on 04/03/2021; Protocol number: 127686/2020v9; Research Ethics Committee, 09/03/2021, Ref 21/WM/0004; IRAS ID: 289982.

A Board Level Intervention to Develop Organisation-Wide Quality Improvement Strategies: Cost-Consequences Analysis in 15 Healthcare Organisations.

BACKGROUND: Hospital boards have statutory responsibility for upholding the quality of care in their organisations. International research on quality in hospitals resulted in a research-based guide to help senior hospital leaders develop and implement quality improvement (QI) strategies, the QUASER Guide. Previous research has established a link between board practices and quality of care; however, to our knowledge, no board-level intervention has been evaluated in relation to its costs and consequences. The aim of this research was to evaluate these impacts when the QUASER Guide was implemented in an organisational development intervention (iQUASER). METHODS: We conducted a 'before and after' cost-consequences analysis (CCA), as part of a mixed methods evaluation. The analysis combined qualitative data collected from 66 interviews, 60 hours of board meeting observations and documents from 15 healthcare organisations, of which 6 took part on iQUASER, and included direct and opportunity costs associated with the intervention. The consequences focused on the development of an organisation-wide QI strategy, progress on addressing 8 dimensions of QI (the QUASER challenges), how organisations compared to benchmarks, engagement with the intervention and progress in the implementation of a QI project. RESULTS: We found that participating organisations made greater progress in developing an organisation-wide QI strategy and became more similar to the high-performing benchmark than the comparators. However, progress in addressing all 8 QUASER challenges was only observed in one organisation. Stronger engagement with the intervention was associated with the implementation of a QI project. On average, iQUASER costed £23 496 per participating organisation, of which approximately 44% were staff time costs. Organisations that engaged less with the intervention had lower than average costs (£21 267 per organisation), but also failed to implement an organisation-wide QI project. CONCLUSION: We found a positive association between level of engagement with the intervention, development of an organisation-wide QI strategy and the implementation of an organisation-wide QI project. Support from the board, particularly the chair and chief executive, for participation in the intervention, is important for organisations to accrue most benefit. A board-level intervention for QI, such as iQUASER, is relatively inexpensive as a proportion of an organisation's budget.

Effect of Breeding Heavier Romney Ewe Lambs at Seven Months of Age on Lamb Production and Efficiency over Their First Three Breeding Seasons.

This experiment examined the effect of breeding heavier ewe lambs on lamb production and their efficiency over their first three breeding seasons. Two groups of ewe lambs were bred at seven months of age at an average pre-breeding live weight of either 47.9 ± 0.36 kg (heavy; n = 135) or 44.9 ± 0.49 kg (control; n = 135). Ewe live weight, number of lambs born and weaned, and lamb live weight were recorded until 39 months of age, and efficiency was calculated for each ewe. Although the number and lamb weaning weight did not differ between treatments over three years, when data were pooled, heavier ewe lambs at breeding weaned a greater number of lambs over the three-year period. The total lamb weaning weight over the three-year period increased by 2% for each additional kilogram at ewe lamb breeding. Breeding heavier ewe lambs had no effect on efficiency. These results suggest that although breeding heavier ewe lambs had a positive effect on lamb production over the three-year period, it had no effect on efficiency. Before final recommendations can be made, lifetime performance and longevity to five years of age of heavier ewe lambs at breeding are required.

The Positive Choices trial: study protocol for a Phase-III RCT trial of a whole-school social marketing intervention to promote sexual health and reduce health inequalities.

BACKGROUND: Positive Choices is a whole-school social marketing intervention to promote sexual health among secondary school students. Intervention comprises school health promotion council involving staff and students coordinating delivery; student survey to inform local tailoring; teacher-delivered classroom curriculum; student-run campaigns; parent information; and review of sexual/reproductive health services to inform improvements. This trial builds on an optimisation/pilot RCT study which met progression criteria, plus findings from another pilot RCT of the Project Respect school-based intervention to prevent dating and relationship violence which concluded such work should be integrated within Positive Choices. Young people carry a disproportionate burden of adverse sexual health; most do not report competence at first sex. Relationships and sex education in schools can contribute to promoting sexual health but effects are small, inconsistent and not sustained. Such work needs to be supplemented by 'whole-school' (e.g. student campaigns, sexual health services) and 'social marketing' (harnessing commercial marketing to social ends) approaches for which there is good review-level evidence but not from the UK. METHODS: We will conduct a cluster RCT across 50 schools (minimum 6440, maximum 8500 students) allocated 1:1 to intervention/control assessing outcomes at 33 months. Our primary outcome is non-competent first sex. Secondary outcomes are non-competent last sex, age at sexual debut, non-use of contraception at first and last sex among those reporting heterosexual intercourse, number of sexual partners, dating and relationship violence, sexually transmitted infections, and pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys. We will recruit 50 school and undertake baseline surveys by March 2022; implement the intervention over the 2022-2024 school years and conduct the economic and process evaluations by July 2024; undertake follow-up surveys by December 2024; complete analyses, all patient and policy involvement and draft the study report by March 2025; and engage in knowledge exchange from December 2024. DISCUSSION: This trial is one of a growing number focused on whole-school approaches to public health in schools. The key scientific output will be evidence about the effectiveness, costs and potential scalability and transferability of Positive Choices. TRIAL REGISTRATION: ISRCTN No: ISRCTN16723909 . Trial registration summary: Date:. Funded by: National Institute for Health Research Public Health Research Programme (NIHR131487). SPONSOR: LSHTM. Public/scientific contact: Chris Bonell. Public title: Positive Choices trial. Scientific title: Phase-III RCT of Positive Choices: a whole-school social marketing intervention to promote sexual health and reduce health inequalities. Countries of recruitment: UK. INTERVENTION: Positive Choices. INCLUSION CRITERIA: Students in year 8 (age 12-13 years) at baseline deemed competent by schools to participate in secondary schools excluding pupil referral units, schools for those with special educational needs and disabilities, and schools with 'inadequate' Ofsted inspections. STUDY TYPE: interventional study with superiority phase III cluster RCT design. Enrollment: 1/9/21-31/3/22. SAMPLE SIZE: 50 schools and 6440-8500 students. Recruitment status: pending. PRIMARY OUTCOME: binary measure of non-competent first sex. SECONDARY OUTCOMES: non-competent last sex; age at sexual debut; non-use of contraception at first and last sex; number of sexual partners; dating and relationship violence (DRV) victimisation; sexually transmitted infections; pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys using adapted versions of the RIPPLE measures. Ethics review: LSHTM research ethics committee (reference 26411). Completion data: 1/3/25. Sharing statement: Data will be made available after the main trial analyses have been completed on reasonable request from researchers with ethics approval and a clear protocol. Amendments to the protocol will be communicated to the investigators, sponsor, funder, research ethics committee, trial registration and the journal publishing the protocol. Amendments affecting participants' experience of the intervention or important amendments affecting the overall design and conduct of the trial will be communicated to participants.

Predicting ewe body condition score using adjusted liveweight for conceptus and fleece weight, height at withers, and previous body condition score record.

The relationship between ewe body condition score (BCS) and liveweight (LW) has been exploited previously to predict the former from LW, LW-change, and previous BCS records. It was hypothesized that if fleece weight and conceptus-free liveweight and LW-change, and in addition, height at withers were used, the accuracy of current approaches to predicting BCS would be enhanced. Ewes born in 2017 (n = 429) were followed from 8 mo to approximately 42 mo of age in New Zealand. Individual ewe data were collected on LW and BCS at different stages of the annual production cycle (i.e., prebreeding, at pregnancy diagnosis, prelambing, and weaning). Additionally, individual lambing dates, ewe fleece weight, and height at withers data were collected. Linear regression models were fitted to predict current BCS at each ewe age and stage of the annual production cycle using two LW-based models, namely, unadjusted for conceptus weight and fleece weight (LW alone1) and adjusted (LW alone2) models. Furthermore, another two models based on a combination of LW, LW-change, previous BCS, and height at withers (combined models), namely, unadjusted (combined1) and adjusted for conceptus and fleece weight (combined2), were fitted. Combined models gave more accurate (with lower root mean square error: RMSE) BCS predictions than models based on LW records alone. However, applying adjusted models did not improve BCS prediction accuracy (or reduce RMSE) or improve model goodness of fit (R 2) (P > 0.05). Furthermore, in all models, both LW-alone and combined models, a great proportion of variability in BCS, could not be accounted for (0.25 ≥ R 2 ≥ 0.83) and there was substantial prediction error (0.33 BCS ≥ RMSE ≥ 0.49 BCS) across age groups and stages of the annual production cycle and over time (years). Therefore, using additional ewe data which allowed for the correction of LW for fleece and conceptus weight and using height at withers as an additional predictor did not improve model accuracy. In fact, the findings suggest that adjusting LW data for conceptus and fleece weight offer no additional value to the BCS prediction models based on LW. Therefore, additional research to identify alternative methodologies to account for individual animal variability is still needed.

Evaluating the effectiveness and cost effectiveness of the 'strengthening families, strengthening communities' group-based parenting programme: study protocol and initial insights.

BACKGROUND: Up to 20% of UK children experience socio-emotional difficulties which can have serious implications for themselves, their families and society. Stark socioeconomic and ethnic inequalities in children's well-being exist. Supporting parents to develop effective parenting skills is an important preventive strategy in reducing inequalities. Parenting interventions have been developed, which aim to reduce the severity and impact of these difficulties. However, most parenting interventions in the UK focus on early childhood (0-10 years) and often fail to engage families from ethnic minority groups and those living in poverty. Strengthening Families, Strengthening Communities (SFSC) is a parenting programme designed by the Race Equality Foundation, which aims to address this gap. Evidence from preliminary studies is encouraging, but no randomised controlled trials have been undertaken so far. METHODS/DESIGN: The TOGETHER study is a multi-centre, waiting list controlled, randomised trial, which aims to test the effectiveness of SFSC in families with children aged 3-18 across seven urban areas in England with ethnically and socially diverse populations. The primary outcome is parental mental well-being (assessed by the Warwick-Edinburgh Mental Well-Being Scale). Secondary outcomes include child socio-emotional well-being, parenting practices, family relationships, self-efficacy, quality of life, and community engagement. Outcomes are assessed at baseline, post intervention, three- and six-months post intervention. Cost effectiveness will be estimated using a cost-utility analysis and cost-consequences analysis. The study is conducted in two stages. Stage 1 comprised a 6-month internal pilot to determine the feasibility of the trial. A set of progression criteria were developed to determine whether the stage 2 main trial should proceed. An embedded process evaluation will assess the fidelity and acceptability of the intervention. DISCUSSION: In this paper we provide details of the study protocol for this trial. We also describe challenges to implementing the protocol and how these were addressed. Once completed, if beneficial effects on both parental and child outcomes are found, the impact, both immediate and longer term, are potentially significant. As the intervention focuses on supporting families living in poverty and those from minority ethnic communities, the intervention should also ultimately have a beneficial impact on reducing health inequalities. TRIAL REGISTRATION: Prospectively registered Randomised Controlled Trial ISRCTN15194500 .

Operational analysis of school-based delivery models to vaccinate children against influenza.

Large-scale immunisation programmes against seasonal influenza are characterised by logistical challenges related to the need for vaccinating large cohorts of people in a short amount of time. Careful operational planning of resources is essential for a successful implementation of such programmes. We focused on the process of child vaccination in schools and analysed the staffing and workflow aspects of a school-aged children vaccination programme in England. Our objectives were to document vaccination processes and analyse times and costs associated with different models deployed across England. We collected data through direct non-participatory observations. Statistical data analysis enabled us to identify potential factors influencing vaccine delivery time and informed the development of a tool to simulate vaccination sessions. Using this tool, we carried out scenario analyses and explored trade-offs between session times and costs in different settings. Our work ultimately supported the local implementation of school-based vaccination.

Ion regulation in a freshwater crab, Potamonautes warreni: The effects of trace metal exposure.

Crustaceans inhabiting metal-contaminated freshwaters are susceptible to toxic insult to their osmoregulatory systems. The main osmoregulatory organs of decapod crustaceans, the gills, are continually bathed in freshwater and are therefore at risk from trace metal impacts. The effects of chronic (21 d) exposure to raised dissolved concentrations of Zn, Cd, Cu and Pb on aspects of hydromineral balance were investigated in Potamonautes warreni, a freshwater crab endemic to rivers in South Africa at potential risk from trace metal contamination from mining operations. Generally, hydromineral balance of P. warreni was tolerant to chronic metal exposures although sublethal cadmium exposure of 860 µg.l-1 for 21 days resulted in a reduced sodium concentration in the haemolymph. A chronic exposure to 43 µg.l-1 cadmium produced an elevated maximum unidirectional sodium uptake, possibly resulting from acclimation to the metal exposure. Branchial Na+/K+-ATPase and V-Type H+-ATPase activity were not affected by chronic in vivo Cd (43 µg.l-1) and Zn (500 µg.l-1) exposures. An important aspect of ameliorating metal toxicity may be through antioxidants and therefore the effects of applying a reducing agent were tested following in vitro metal treatment. Inhibition of Na+/K+-ATPase could be prevented by pre-incubation with a reducing agent, indicating the importance of antioxidants in reducing metal toxicity in this species. Although this study demonstrates the physiological resilience of P. warreni to dissolved trace metal impacts, the energetic consequences of long-term exposure are as yet not known.

How to Cost the Implementation of Major System Change for Economic Evaluations: Case Study Using Reconfigurations of Specialist Cancer Surgery in Part of London, England.

BACKGROUND: Studies have been published regarding the impact of major system change (MSC) on care quality and outcomes, but few evaluate implementation costs or include them in cost-effectiveness analysis (CEA). This is despite large potential costs of MSC: change planning, purchasing or repurposing assets, and staff time. Implementation costs can influence implementation decisions. We describe our framework and principles for costing MSC implementation and illustrate them using a case study. METHODS: We outlined MSC implementation stages and identified components, using a framework conceived during our work on MSC in stroke services. We present a case study of MSC of specialist surgery services for prostate, bladder, renal and oesophagogastric cancers, focusing on North Central and North East London and West Essex. Health economists collaborated with qualitative researchers, clinicians and managers, identifying key reconfiguration stages and expenditures. Data sources (n = approximately 100) included meeting minutes, interviews, and business cases. National Health Service (NHS) finance and service managers and clinicians were consulted. Using bottom-up costing, items were identified, and unit costs based on salaries, asset costs and consultancy fees assigned. Itemised costs were adjusted and summed. RESULTS: Cost components included options appraisal, bidding process, external review; stakeholder engagement events; planning/monitoring boards/meetings; and making the change: new assets, facilities, posts. Other considerations included hospital tariff changes; costs to patients; patient population; and lifetime of changes. Using the framework facilitated data identification and collection. The total adjusted implementation cost was estimated at £7.2 million, broken down as replacing robots (£4.0 million), consultancy fees (£1.9 million), staff time costs (£1.1 million) and other costs (£0.2 million). CONCLUSIONS: These principles can be used by funders, service providers and commissioners planning MSC and researchers evaluating MSC. Health economists should be involved early, alongside qualitative and health-service colleagues, as retrospective capture risks information loss. These analyses are challenging; many cost factors are difficult to identify, access and measure, and assumptions regarding lifetime of the changes are important. Including implementation costs in CEA might make MSC appear less cost effective, influencing future decisions. Future work will incorporate this implementation cost into the full CEAs of the London Cancer MSC. TRIAL REGISTRATION: Not applicable.

The Effect of Age of Dam and Birth Rank on the Reproductive Performance of Ewes as One- and Two-Year-Olds.

Currently, 30-43% of New Zealand sheep farmers breed their ewe lambs, but few retain the offspring as replacements for their flock. No difference in lamb production as a yearling among singletons and twins born to ewe lambs and twins born to mature ewes has been reported, provided the ewe lambs had reached the 60-65% of their likely mature weight prior to breeding at seven to eight months of age. The aim of this experiment was to determine the lamb production from singletons and twins born to ewe lambs and twins born to mature ewes during their first two years of lambing. The experiment included 8-month-old ewes born as twins to mature ewes (M2, n = 135), singletons born to ewe lambs (L1, n = 135), and twins born to ewe lambs (L2, n = 88), bred during the same period to the same rams, over two years. The efficiency of lamb production (total litter weight at weaning divided by the pre-breeding weight of the ewe, for all ewes presented for breeding) after two years of production was not significantly different (p > 0.05) among the groups (0.40 ± 0.02, 0.39 ± 0.02, and 0.39 ± 0.03, for M2, L1, and L2, respectively).

The implementation of remote home monitoring models during the COVID-19 pandemic in England.

BACKGROUND: There is a paucity of evidence for the implementation of remote home monitoring for COVID-19 infection. The aims of this study were to identify the key characteristics of remote home monitoring models for COVID-19 infection, explore the experiences of staff implementing these models, understand the use of data for monitoring progress against outcomes, and document variability in staffing and resource allocation. METHODS: This was a multi-site mixed methods study conducted between July and August 2020 that combined qualitative and quantitative approaches to analyse the implementation and impact of remote home monitoring models developed during the first wave of the COVID-19 pandemic in England. The study combined interviews (n = 22) with staff delivering these models across eight sites in England with the collection and analysis of data on staffing models and resource allocation. FINDINGS: The models varied in relation to the healthcare settings and mechanisms used for patient triage, monitoring and escalation. Implementation was embedded in existing staff workloads and budgets. Good communication within clinical teams, culturally-appropriate information for patients/carers and the combination of multiple approaches for patient monitoring (app and paper-based) were considered facilitators in implementation. The mean cost per monitored patient varied from £400 to £553, depending on the model. INTERPRETATION: It is necessary to provide the means for evaluating the effectiveness of these models, for example, by establishing comparator data. Future research should also focus on the sustainability of the models and patient experience (considering the extent to which some of the models exacerbate existing inequalities in access to care).

Dental attendance and behavioural pathways to adult oral health inequalities.

BACKGROUND: While inequalities in oral health are documented, little is known about the extent to which they are attributable to potentially modifiable factors. We examined the role of behavioural and dental attendance pathways in explaining oral health inequalities among adults in England, Wales and Northern Ireland. METHODS: Using nationally representative data, we analysed inequalities in self-rated oral health and number of natural teeth. Highest educational attainment, equivalised household income and occupational social class were used to derive a latent socioeconomic position (SEP) variable. Pathways were dental attendance and behaviours (smoking and oral hygiene). We used structural equation modelling to test the hypothesis that SEP influences oral health directly and also indirectly via dental attendance and behavioural pathways. RESULTS: Lower SEP was directly associated with fewer natural teeth and worse self-rated oral health (standardised path coefficients, -0.21 (SE=0.01) and -0.10 (SE=0.01), respectively). We also found significant indirect effects via behavioural factors for both outcomes and via dental attendance primarily for self-rated oral health. While the standardised parameters of total effects were similar between the two outcomes, for number of teeth, the estimated effect of SEP was mostly direct while for self-rated oral health, it was almost equally split between direct and indirect effects. CONCLUSION: Reducing inequalities in dental attendance and health behaviours is necessary but not sufficient to tackle socioeconomic inequalities in oral health.

A model-based cost-utility analysis of multi-professional simulation training in obstetric emergencies.

OBJECTIVE: To determine the cost-utility of a multi-professional simulation training programme for obstetric emergencies-Practical Obstetric Multi-Professional Training (PROMPT)-with a particular focus on its impact on permanent obstetric brachial plexus injuries (OBPIs). DESIGN: A model-based cost-utility analysis. SETTING: Maternity units in England. POPULATION: Simulated cohorts of individuals affected by permanent OBPIs. METHODS: A decision tree model was developed to estimate the cost-utility of adopting annual, PROMPT training (scenario 1a) or standalone shoulder dystocia training (scenario 1b) in all maternity units in England compared to current practice, where only a proportion of English units use the training programme (scenario 2). The time horizon was 30 years and the analysis was conducted from an English National Health Service (NHS) and Personal Social Services perspective. A probabilistic sensitivity analysis was performed to account for uncertainties in the model parameters. MAIN OUTCOME MEASURES: Outcomes for the entire simulated period included the following: total costs for PROMPT or shoulder dystocia training (including costs of OBPIs), number of OBPIs averted, number of affected adult/parental/dyadic quality adjusted life years (QALYs) gained and the incremental cost per QALY gained. RESULTS: Nationwide PROMPT or shoulder dystocia training conferred significant savings (in excess of £1 billion ($1.5 billion)) compared to current practice, resulting in cost-savings of at least £1 million ($1.5 million) per any type of QALY gained. The probabilistic sensitivity analysis demonstrated similar findings. CONCLUSION: In this model, national implementation of multi-professional simulation training for obstetric emergencies (or standalone shoulder dystocia training) in England appeared to both be cost-saving when evaluating their impact on permanent OBPIs.

Toenail selenium, plasma selenoprotein P and risk of advanced prostate cancer: A nested case-control study.

Low selenium status may be associated with increased risk of prostate cancer (PC), particularly aggressive PC, and variation in selenoprotein genes may constitute an important modifying factor. We aimed to investigate the association between two selenium status biomarkers [toenail selenium, plasma selenoprotein P (SELENOP)] and risk of advanced, high-grade and advanced-stage PC. We further studied whether variations in selenoprotein genes were associated with PC risk and selenium biomarker concentrations. In the "Diet, Cancer and Health" cohort, 27 178 men aged 50 to 65 years were enrolled from 1993 to 1997. Between baseline and 2012, 1160 cohort participants were diagnosed with advanced PC; among these 462 had high-grade and 281 had advanced-stage disease at diagnosis. Each case was risk set-matched to one control. Toenail selenium and plasma SELENOP concentrations were measured by neutron activation analysis and a SELENOP-ELISA, respectively, and genotyping was performed for 27 selected single nucleotide polymorphisms (SNPs) in 12 selenium pathway genes (including seven selenoproteins) by allele-specific PCR. Toenail selenium and circulating SELENOP concentrations were not associated with advanced, high-grade or advanced-stage PC. After adjustment for multiple testing, none of the genes were associated with PC risk. Neither toenail selenium nor plasma SELENOP was associated with advanced, high-grade or advanced-stage PC.

Predictors of patient preference for either whole body magnetic resonance imaging (WB-MRI) or CT/ PET-CT for staging colorectal or lung cancer.

INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer. METHODS: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression. RESULTS: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute. CONCLUSIONS: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference.