An evaluation of a health care programme approach to commissioning stroke services in Gateshead and South Tyneside

MD ThesisIntroduction The NHS emphasises programme approaches to commissioning (Health Improvement Programmes and National Service Frameworks) but research is limited. I evaluated the Health Care Programme Approach (HCPA) for stroke whose individual elements are: a co-ordinating group; a co-ordinator; a technical document; and agreement of priorities. Methods 1 Four rounds of interviews with managers and clinicians; observation at meetings; analysis of documentary sources. 2 Quantitative indicators of progress measured at two time points. 3 Estimation of the Programme Budget and Transaction Costs from published sources and local data. 4 Interviews with Directors of Public Health from nine comparator districts. Results 1A structured process led to a set of priorities, which were widely accepted across all agencies, allowing the co-ordinating group to focus on facilitating change. This group took two years to reach a stage where it could change services. Most peoples upportedth e approachb ut were not alwaysc lear aboutt he process. 2 The indicators showed improvements in some aspects of care. 3 The programme budget was £IOm, mostly in long-term care (£5.5m) and hospital care (£3m). The transaction costs amounted to 0.25% of the programme budget. Preface 4 All comparator districts reported changes to commissioning and improvements in stroke services, but I found more widespread change in the study district. Discussion The detailed description of process, and use of multiple methods, gives strength to the findings. A collaborative approach has developed across the NHS during the period of this study making the findings highly relevant. There were important lessons for multiagency groups including: the time needed to function effectively; the need for individuals to clarify whether they represent an organisation or their own perspective; the need to review the group remit and the group's routes of communication; and the ability to adapt to changes in national policy while focusing on improving the health of the patients who fall within the programme. Keywords Planning, Purchasing, Commissioning, Stroke Services, Health Care Programme Approach, Evidence-Based, Multiagency Collaboration, Triangulation, Evaluation, Case Study.NHSE Northern and Yorkshire, Research and Development: Stroke Association

Impact of financial incentives on alcohol intervention delivery in primary care: a mixed-methods study

Background Local and national financial incentives were introduced in England between 2008 and 2015 to encourage screening and brief alcohol intervention delivery in primary care. We used routine Read Code data and interviews with General Practitioners (GPs) to assess their impact. Methods A sequential explanatory mixed-methods study was conducted in 16 general practices representing 106,700 patients and 99 GPs across two areas in Northern England. Data were extracted on screening and brief alcohol intervention delivery for 2010-11 and rates were calculated by practice incentive status. Semi-structured interviews with 14 GPs explored which factors influence intervention delivery and recording in routine consultations. Results Screening and brief alcohol intervention rates were higher in financially incentivised compared to non-incentivised practices. However absolute rates were low across all practices. Rates of short screening test administration ranged from 0.05% (95% CI: 0.03-0.08) in non-incentivised practices to 3.92% (95% CI: 3.70-4.14) in nationally incentivised practices. For the full AUDIT, rates were also highest in nationally incentivised practices (3.68%, 95% CI: 3.47-3.90) and lowest in non-incentivised practices (0.17%, 95% CI: 0.13-0.22). Delivery of alcohol interventions was highest in practices signed up to the national incentive scheme (9.23%, 95% CI: 8.91-9.57) and lowest in non-incentivised practices (4.73%, 95% CI: 4.50-4.96). GP Interviews highlighted a range of influences on alcohol intervention delivery and subsequent recording including: the hierarchy of different financial incentive schemes; mixed belief in the efficacy of alcohol interventions; the difficulty of codifying complex conditions; and GPs’ beliefs about patient-centred practice. Conclusions Financial incentives have had some success in encouraging screening and brief alcohol interventions in England, but levels of recorded activity remain low. To improve performance, future policies must prioritise alcohol prevention work within the quality and outcomes framework, and address the values, attitudes and beliefs that shape how GPs’ provide care

Talin1 and Rap1 are critical for osteoclast function

To determine talin1's role in osteoclasts, we mated TLN1(fl/fl) mice with those expressing cathepsin K-Cre (CtsK-TLN1) to delete the gene in mature osteoclasts or with lysozyme M-Cre (LysM-TLN1) mice to delete TLN1 in all osteoclast lineage cells. Absence of TLN1 impairs macrophage colony-stimulating factor (M-CSF)-stimulated inside-out integrin activation and cytoskeleton organization in mature osteoclasts. Talin1-deficient precursors normally express osteoclast differentiation markers when exposed to M-CSF and receptor activator of nuclear factor κB (RANK) ligand but attach to substrate and migrate poorly, arresting their development into mature resorptive cells. In keeping with inhibited resorption, CtsK-TLN1 mice exhibit an ∼5-fold increase in bone mass. Osteoclast-specific deletion of Rap1 (CtsK-Rap1), which promotes talin/β integrin recognition, yields similar osteopetrotic mice. The fact that the osteopetrosis of CtsK-TLN1 and CtsK-Rap1 mice is substantially more severe than that of those lacking αvβ3 is likely due to added failed activation of β1 integrins. In keeping with osteoclast dysfunction, mice in whom talin is deleted late in the course of osteoclastogenesis are substantially protected from ovariectomy-induced osteoporosis and the periarticular osteolysis attending inflammatory arthritis. Thus, talin1 and Rap1 are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss

The response of Tampa Bay to a legacy mining nutrient release in the year following the event

IntroductionCultural eutrophication threatens numerous ecological and economical resources of Florida’s coastal ecosystems, such as beaches, mangroves, and seagrasses. In April 2021, an infrastructure failure at the retired Piney Point phosphorus mining retention reservoir garnered national attention, as 814 million liters of nutrient rich water were released into Tampa Bay, Florida over 10 days. The release of nitrogen and phosphorus-rich water into Tampa Bay – a region that had been known as a restoration success story since the 1990s – has highlighted the potential for unexpected challenges for coastal nutrient management.MethodsFor a year after the release, we sampled bi-weekly at four sites to monitor changes in nutrients, stable isotopes, and phytoplankton communities, complemented with continuous monitoring by multiparameter sondes. Our data complement the synthesis efforts of regional partners, the Tampa Bay and Sarasota Bay Estuary Programs, to better understand the effects of anthropogenic nutrients on estuarine health.ResultsPhytoplankton community structure indicated an initial diatom bloom that dissipated by the end of April 2021. In the summer, the bay was dominated by Karenia brevis, with conditions improving into the fall. To determine if there was a unique carbon (C) and nitrogen (N) signature of the discharge water, stable isotope values of carbon (δ13C) and nitrogen (δ15N) were analyzed in suspended particulate material (SPM). The δ15N values of the discharge SPM were −17.88‰ ± 0.76, which is exceptionally low and was unique relative to other nutrient sources in the region. In May and early June of 2021, all sites exhibited a decline in the δ15N values of SPM, suggesting that discharged N was incorporated into SPM after the event. The occurrence of very low δ15N values at the reference site, on the Gulf Coast outside of the Bay, indicates that some of the discharge was transported outside of Tampa Bay.DiscussionThis work illustrates the need for comprehensive nutrient management strategies to assess and manage the full range of consequences associated with anthropogenic nutrient inputs into coastal ecosystems. Ongoing and anticipated impacts of climate change – such as increasing tropical storm intensity, temperatures, rainfall, and sea level rise – will exacerbate this need

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Public Health Observatories in England: the first three years

Public health observatories (PHOs) were created in England in 2000. Since then they have been engaged in a variety of activities to support the health improvement agenda in England. This article describes these activities, the key responsibilities and outputs of PHOs. It also describes the links with other observatories in Europe

A note on ERM membership and the efficiency of the London Stock Exchange

The behaviour of the FTSE 30 share index is examined over a period from November 1988 to May 1994. We examine whether the index exhibits different time series behaviour during the time that Sterling belonged to the ERM to that observed in the pre- and post-ERM period. We show that the random walk behaviour, which would be expected under the Efficient Markets Hypothesis (EMH), occurs during the period when Sterling belonged to the ERM but for pre- and post-ERM membership period the index does not appear to follow a random walk.