Evaluation of a multidisciplinary adult integrated respiratory service in the UK.

Rationale, aims and objectives: Care integration, particularly for patients with long-term chronic conditions has been viewed as a key imperative for service improvement over the last decade [1]. In common with other industrialised nations, major care providers such as the National Health Service (NHS) in the United Kingdom (UK) have undertaken service evaluation to identify factors for effective integrated care in the context of increasing demand but also cost-constraints. The aim of this paper is to report on an early process evaluation of a newly established Adult Integrated Respiratory Service (AIRS) in three localities in England. Method: Applied qualitative methods using semi-structured interviews with clinical practitioners (n=19) plus focus group with service users (n=5). University research ethics approval was secured. Findings: Despite finding staff commitment and enthusiasm for a new regional approach, as well as a very positive acclaim from service users, the study highlighted personal and organisational issues and concerns during the first four months of service implementation. The analysis revealed four inter-related themes: service in transition; resistance to change; communication; and challenges to integrated working. The findings support conceptual and organisational elements of integrated care described elsewhere [2, 3]. The role of leadership and change management in the successful implementation of integrated care is explored. Conclusions: The findings from a regional adult integrated respiratory service evaluation in England highlights the potential of collective leadership with authentic involvement of all stakeholders to effect successful change to build locally owned models for integrated care. Further longitudinal research would yield valuable insights as the service evolves

Dorset Adult Integrated Care Service (DAIRS): Service Evalaution

EXECUTIVE SUMMARY This early process evaluation of the newly established Dorset Adult Integrated Respiratory Service (DAIRS) in three localities in Dorset was conducted by Bournemouth University using a mixed-methods approach. Our evaluation showed staff commitment and enthusiasm for a pan-Dorset approach to respiratory care and a very positive acclaim from service users. Mindful of the fact that DAIRS had been in operation for four months only, the evaluation flags up strengths and issues of concern at the initial stages of service implementation. Discussion of the findings has been linked with current thinking to emerge in the White Paper from NHS Improving Quality around service improvement and change management (Bevan & Fairman, 2014). Given that DAIRS has been commissioned in the first instance for a period of two years, this early evaluation will be valuable for stakeholders to address the issues raised in a timely manner. Recommendations 1. Build upon the high levels of satisfaction to engage service user users more widely in the on-going development of DAIRS. 2. Shared documentation needs to be agreed and implemented as soon as possible, including the DAIRS card. 3. DAIRS should be officially launched with appropriate information for different stakeholders: service users, community staff and non-DAIRS hospital staff. 4. The change process should be actively managed; concerns and challenges expressed by participants should be acknowledged and a supportive environment provided for collaborative problem-solving. 5. Consider selection and use of grass roots ‘change champions’ across the sites and disciplines to facilitate a more inclusive model of organisational change. 6. Further integration between localities should be explored particularly around staff education, as well as to facilitate on-going peer support. 7. New staff would benefit from being supernumerary for their first month and visiting neighbouring DAIRS localities. 8. Inclusion and exclusion criteria need to be revisited to ensure a shared understanding amongst DAIRS staff, particularly around co-morbidities. 9. Information and service provision concerning emotional support for service users and carers needs to be reviewed. 10. The current Single Point of Access System (SPOA) should be reviewed to improve compliance. 11. Information Technology (IT) systems and possibilities for joint DAIRS systems should be explored. 12. Perceived financial inequities need to be addressed in service planning. 13. Our evaluation provides a base-line for future work, a further more comprehensive evaluation after two years of DAIRS operation is needed to inform future funding and service development. Suggested factors to include: • Outcome data • Cross-locality service user involvement (avoiding winter peak time), using systematic PREM questionnaire distribution processes. • Community staff perspectives. • Input from related respiratory services, currently not part of DAIRS. • Investigation of impact of a differing skill mix across localities. • More detailed service user feedback. • Evaluation of staff education (DAIRS and non-DAIRS)

An evaluation of the progress made towards the implementation of treatment summaries for cancer patients across Wessex

This report details an evaluation of the implementation of treatment summaries for cancer patients across the Wessex Deanery, encompassing Hampshire, Dorset and the Isle of Wight. The service evaluation commenced at the end of September 2015 and this report presents the progress made towards the implementation of cancer treatment summaries (CT) across the Wessex Deanery and service users’ experiences of receiving the TSs from two NHS Trusts in the catchment area. The survey results present the progress that has been made in the first six months of implementation and include descriptive data relating to the progress and process of implementation. The qualitative findings from an analysis of service user experience are presented and the findings from the evaluation are discussed in the context of national policy and the wider literature

The H3.3 chaperone Hira complex orchestrates oocyte developmental competence

Successful reproduction requires an oocyte competent to sustain early embryo development. By the end of oogenesis, the oocyte has entered a transcriptionally silenced state, the mechanisms and significance of which remain poorly understood. Histone H3.3, a histone H3 variant, has unique cell cycle-independent functions in chromatin structure and gene expression. Here, we have characterised the H3.3 chaperone Hira/Cabin1/Ubn1 complex, showing that loss of function of any of these subunits causes early embryogenesis failure in mouse. Transcriptome and nascent RNA analyses revealed that transcription is aberrantly silenced in mutant oocytes. Histone marks, including H3K4me3 and H3K9me3, are reduced and chromatin accessibility is impaired in Hira/Cabin1 mutants. Misregulated genes in mutant oocytes include Zscan4d, a two-cell specific gene involved in zygote genome activation. Overexpression of Zscan4 in the oocyte partially recapitulates the phenotypes of Hira mutants and Zscan4 knockdown in Cabin1 mutant oocytes partially restored their developmental potential, illustrating that temporal and spatial expression of Zscan4 is fine-tuned at the oocyte-to-embryo transition. Thus, the H3.3 chaperone Hira complex has a maternal effect function in oocyte developmental competence and embryogenesis, through modulating chromatin condensation and transcriptional quiescence

Feasibility of novel adult tuberculosis vaccination in South Africa: a cost-effectiveness and budget impact analysis.

Early trials of novel vaccines against tuberculosis (TB) in adults have suggested substantial protection against TB. However, little is known about the feasibility and affordability of rolling out such vaccines in practice. We conducted expert interviews to identify plausible vaccination implementation strategies for the novel M72/AS01E vaccine candidate. The strategies were defined in terms of target population, coverage, vaccination schedule and delivery mode. We modelled these strategies to estimate long-term resource requirements and health benefits arising from vaccination over 2025-2050. We presented these to experts who excluded strategies that were deemed infeasible, and estimated cost-effectiveness and budget impact for each remaining strategy. The four strategies modelled combined target populations: either everyone aged 18-50, or all adults living with HIV, with delivery strategies: either a mass campaign followed by routine vaccination of 18-year olds, or two mass campaigns 10 years apart. Delivering two mass campaigns to all 18-50-year olds was found to be the most cost-effective strategy conferring the greatest net health benefit of 1.2 million DALYs averted having a probability of being cost-effective of 65-70%. This strategy required 38 million vaccine courses to be delivered at a cost of USD 507 million, reducing TB-related costs by USD 184 million while increasing ART costs by USD 79 million. A suitably designed adult TB vaccination programme built around novel TB vaccines is likely to be cost-effective and affordable given the resource and budget constraints in South Africa

The Proper Motion of the Globular Cluster NGC 6553 and of Bulge Stars with HST

WFPC2 images obtained with the Hubble Space telescope 4.16 years apart have allowed us to measure the proper motion of the metal rich globular cluster NGC 6553 with respect to the background bulge stars. With a space velocity of (${\Pi}, {\Theta}, W$) = (-3.5, 230, -3) km s$^{-1}$, NGC 6553 follows the mean rotation of both disk and bulge stars at a Galactocentric distance of 2.7 kpc. While the kinematics of the cluster is consistent with either a bulge or a disk membership, the virtual identity of its stellar population with that of the bulge cluster NGC6528 makes its bulge membership more likely. The astrometric accuracy is high enough for providing a measure of the bulge proper motion dispersion and confirming its rotation. A selection of stars based on the proper motions produced an extremely well defined cluster color-magnitude diagram (CMD), essencially free of bulge stars. The improved turnoff definition in the decontaminated CMD confirms an old age for the cluster (~13 Gyr) indicating that the bulge underwent a rapid chemical enrichment while being built up at in the early Universe. An additional interesting feature of the cluster color-magnitude diagram is a significant number of blue stragglers stars, whose membership in the cluster is firmly established from their proper motions.Comment: version with full-page figure

Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5):a four-arm, multicentre, randomised, phase 2 trial

BackgroundPatients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery.MethodsESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m2 on days 1, 8, and 15, and oral capecitabine 830 mg/m2 twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, folinic acid given according to local practice, and fluorouracil 400 mg/m2 bolus injection on days 1 and 15 followed by 2400 mg/m2 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m2 twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete.FindingsBetween Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0-12·4). 1-year overall survival was 39% (95% CI 24-61) for immediate surgery, 78% (60-100) for gemcitabine plus capecitabine, 84% (70-100) for FOLFIRINOX, and 60% (37-97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19-58) for immediate surgery and 59% (46-74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28-0·98], p=0·016). Three patients reported local disease recurrence (two in the immediate surgery group and one in the FOLFIRINOX group). 78 (91%) patients were included in the safety set and assessed for toxicity events. 19 (24%) of 78 patients reported a grade 3 or worse adverse event (two [7%] of 28 patients in the immediate surgery group and 17 [34%] of 50 patients in the neoadjuvant therapy groups combined), the most common of which were neutropenia, infection, and hyperglycaemia.InterpretationRecruitment was challenging. There was no significant difference in resection rates between patients who underwent immediate surgery and those who underwent neoadjuvant therapy. Short-course (8 week) neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Neoadjuvant chemotherapy with either gemcitabine plus capecitabine or FOLFIRINOX had the best survival compared with immediate surgery. These findings support the use of short-course neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma.FundingCancer Research UK

Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.</p

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity