The development of a fully integrated, outcomes based, whole system framework of public sector commissioning for the health and wellbeing of the population.

Integration of public services is a key policy objective for every government and policy maker, ever increasingly so. However, the history of successful public sector integration is one of failed ambition. At a time when public services face increased demand and significant budget pressures the desire for integration of public services has grown, especially health and social care integration. This report provides an analysis on whether a new model of whole system integrated commissioning across the full range of public services is required in order to effectively improve the health and wellbeing of the population. The research draws together a wide range of academic material and grey literature in order to consider the potential of a new model. The report considers the context of a number of public policy areas in order to articulate the art of the possible, namely focusing on the NHS, adult social care and public health but also considering the potential in areas such as children’s social care, housing and police and fire services. The report also outlines a proposition for the future model of integrated commissioning, in order to develop a framework against which the benefits and challenges can be considered. Finally, the report makes the case for the integration of public service commissioning and then outlines key salient issues for consideration during the potential implementation of a new model. In conclusion, this paper argues that current attempts to integrate health and social care are restricted by the structure in which public services in England are commissioned: a disparate range of organisations managing budgets, placing organisational priorities above achievement of health and wellbeing outcomes. It argues that if policy makers are to make the required step change needed to deliver a 21st century model of public services that is centred on the health and wellbeing of the population, prioritising the wider determinants of health, a significant redesign of the structure of public service commissioning is required. Furthermore, any new model of public sector commissioning should be centered on the principles of: single budget holder, population based, outcomes focused and localised. The report recognises that the proposal under consideration requires significant change and investment, and any proposal is only as good as its implementation. The analysis also highlights weaknesses in evidence base for integration generally, meaning a case for change is based logical implications for the benefit to society as a whole

The Effects of Beetroot Juice on Blood Pressure, Microvascular Function and Large-Vessel Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Pilot Study in Healthy Older Adults.

Dietary nitrate (NO ) has been reported to improve endothelial function (EF) and blood pressure (BP). However, most studies only assess large-vessel EF with little research on the microvasculature. Thus, the aim of the present pilot study is to examine NO supplementation on microvascular and large-vessel EF and BP. Twenty older adults (63 ± 6 years) were randomized to a beetroot juice (BRJ) or placebo (PLA) group for 28 (±7) days and attended three laboratory visitations. Across visitations, blood pressure, microvascular function and large-vessel EF were assessed by laser Doppler imaging (LDI) with iontophoresis of vasoactive substances and flow-mediated dilatation (FMD), respectively. Plasma NO concentrations, BP and the presence of NO reducing bacteria were also assessed. Plasma NO increased following two weeks of BRJ supplementation (p = 0.04) along with a concomitant decrease in systolic and diastolic BP of approximately −6 mmHg and −4 mmHg, respectively (p = 0.04; p = 0.01, respectively). BP remained unchanged in the PLA group. There were no significant differences in endothelium-dependent or endothelium-independent microvascular responses between groups. FMD increased by 1.5% following two weeks of BRJ (p = 0.04), with only a minimal (0.1%) change for the PLA group. In conclusion, this pilot study demonstrated that medium-term BRJ ingestion potentially improves SBP, DBP and large-vessel EF in healthy older adults. The improvements observed in the present study are likely to be greater in populations presenting with endothelial dysfunction. Thus, further prospective studies are warranted in individuals at greater risk for cardiovascular disease

Complete coding sequence of a case of chikungunya virus imported into Australia

A case of chikungunya virus infection was imported from India into Australia in late 2016. Infection was diagnosed by real-time reverse transcription-PCR and confirmed by culture isolation and genome sequencing. Phylogenetic analysis of the genome sequence indicated that the virus grouped with the east/central/south African genotype

Malaria surveillance from both ends: concurrent detection of Plasmodium falciparum in saliva and excreta harvested from Anopheles mosquitoes

Background: Malaria is the most important vector-borne disease in the world. Epidemiological and ecological studies of malaria traditionally utilize detection of Plasmodium sporozoites in whole mosquitoes or salivary glands by microscopy or serological or molecular assays. However, these methods are labor-intensive, and can over- or underestimate mosquito transmission potential. To overcome these limitations, alternative sample types have been evaluated for the study of malaria. It was recently shown that Plasmodium could be detected in saliva expectorated on honey-soaked cards by Anopheles stephensi, providing a better estimate of transmission risk. We evaluated whether excretion of Plasmodium falciparum nucleic acid by An. stephensi correlates with expectoration of parasites in saliva, thus providing an additional sample type for estimating transmission potential. Mosquitoes were exposed to infectious blood meals containing cultured gametocytes, and excreta collected at different time points post-exposure. Saliva was collected on honey-soaked filter paper cards, and salivary glands were dissected and examined microscopically for sporozoites. Excreta and saliva samples were tested by real time polymerase chain reaction (RT-rtPCR). Results: Plasmodium falciparum RNA was detected in mosquito excreta as early as four days after ingesting a bloodmeal containing gametocytes. Once sporogony (the development of sporozoites) occurred, P. falciparum RNA was detected concurrently in both excreta and saliva samples. In the majority of cases, no difference was observed between the Ct values obtained from matched excreta and saliva samples, suggesting that both samples provide equally sensitive results. A positive association was observed between the molecular detection of the parasites in both samples and the proportion of mosquitoes with sporozoites in their salivary glands from each container. No distinguishable parasites were observed when excreta samples were stained and microscopically analyzed. Conclusions: Mosquito saliva and excreta are easily collected and are promising for surveillance of malaria-causing parasites, especially in low transmission settings or in places where arboviruses co-circulate

Evaluation of a national complex oral health improvement programme: a population data linkage cohort study in Scotland

Objectives Child dental caries is a global public health challenge with high prevalence and wide inequalities. A complex public health programme (Childsmile) was established. We aimed to evaluate the reach of the programme and its impact on child oral health. Setting Education, health and community settings, Scotland-wide. Interventions Childsmile (national oral health improvement programme) interventions: nursery-based fluoride varnish applications (FVAs) and supervised daily toothbrushing, community-based Dental Health Support Worker (DHSW) contacts and primary care dental practice visits—delivered to the population via a proportionate universal approach. Participants: 50 379 children (mean age=5.5 years, SD=0.3) attending local authority schools (2014/2015). Design: Population-based individual child-level data on four Childsmile interventions linked to dental inspection survey data to form a longitudinal cohort. Logistic regression assessed intervention reach and the independent impact of each intervention on caries experience, adjusting for age, sex and area-based Scottish Index of Multiple Deprivation (SIMD). Outcome measures: Reach of the programme is defined as the percentage of children receiving each intervention at least once by SIMD fifth. Obvious dental caries experience (presence/absence) is defined as the presence of decay (into dentine), missing (extracted) due to decay or filled deciduous teeth. Results: 15 032 (29.8%) children had caries experience. The universal interventions had high population reach: nursery toothbrushing (89.1%), dental practice visits (70.5%). The targeted interventions strongly favoured children from the most deprived areas: DHSW contacts (SIMD 1: 29.5% vs SIMD 5: 7.7%), nursery FVAs (SIMD 1: 75.2% vs SIMD 5: 23.2%). Odds of caries experience were markedly lower among children participating in nursery toothbrushing (>3 years, adjusted OR (aOR)=0.60; 95% CI 0.55 to 0.66) and attending dental practice (≥6 visits, aOR=0.55; 95% CI 0.50 to 0.61). The findings were less clear for DHSW contacts. Nursery FVAs were not independently associated with caries experience. Conclusions: The universal interventions, nursery toothbrushing and regular dental practice visits were independently and most strongly associated with reduced odds of caries experience in the cohort, with nursery toothbrushing having the greatest impact among children in areas of high deprivation

Nucleic Acid Preservation Card Surveillance Is Effective for Monitoring Arbovirus Transmission on Crocodile Farms and Provides a One Health Benefit to Northern Australia

The Kunjin strain of West Nile virus (WNVKUN) is a mosquito-transmitted flavivirus that can infect farmed saltwater crocodiles in Australia and cause skin lesions that devalue the hides of harvested animals. We implemented a surveillance system using honey-baited nucleic acid preservation cards to monitor WNVKUN and another endemic flavivirus pathogen, Murray Valley encephalitis virus (MVEV), on crocodile farms in northern Australia. The traps were set between February 2018 and July 2020 on three crocodile farms in Darwin (Northern Territory) and one in Cairns (North Queensland) at fortnightly intervals with reduced trapping during the winter months. WNVKUN RNA was detected on all three crocodile farms near Darwin, predominantly between March and May of each year. Two of the NT crocodile farms also yielded the detection of MVE viral RNA sporadically spread between April and November in 2018 and 2020. In contrast, no viral RNA was detected on crocodile farms in Cairns during the entire trapping period. The detection of WNVKUN and MVEV transmission by FTATM cards on farms in the Northern Territory generally correlated with the detection of their transmission to sentinel chicken flocks in nearby localities around Darwin as part of a separate public health surveillance program. While no isolates of WNVKUN or MVEV were obtained from mosquitoes collected on Darwin crocodile farms immediately following the FTATM card detections, we did isolate another flavivirus, Kokobera virus (KOKV), from Culex annulirostris mosquitoes. Our studies support the use of the FTATM card system as a sensitive and accurate method to monitor the transmission of WNVKUN and other arboviruses on crocodile farms to enable the timely implementation of mosquito control measures. Our detection of MVEV transmission and isolation of KOKV from mosquitoes also warrants further investigation of their potential role in causing diseases in crocodiles and highlights a “One Health” issue concerning arbovirus transmission to crocodile farm workers. In this context, the introduction of FTATM cards onto crocodile farms appears to provide an additional surveillance tool to detect arbovirus transmission in the Darwin region, allowing for a more timely intervention of vector control by relevant authorities

Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial

Background Treatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS). Methods/design FLAIR is a phase III, multicentre, randomised, controlled, open, parallel-group trial in patients with previously untreated CLL. A total of 754 participants will be randomised on a 1:1 basis to receive standard therapy with FCR or IR. Participants randomised to FCR will receive a maximum of six 28-day treatment cycles. Participants randomised to IR will receive six 28-day cycles of rituximab, and ibrutinib taken daily for 6 years until minimal residual disease (MRD) negativity has been recorded for the same amount of time as it took to become MRD negative, or until disease progression. The primary endpoint is PFS according to the International Workshop on CLL (IWCLL) criteria. Secondary endpoints include: overall survival; proportion of participants with undetectable MRD; response to therapy by IWCLL criteria; safety and toxicity; health-related quality of life (QoL); and cost-effectiveness. Discussion The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of PFS, and whether toxicity rates are favourable. Trial registration ISRCTN01844152. Registered on 8 August 2014, EudraCT number 2013-001944-76. Registered on 26 April 2013

GUDMAP - An Online GenitoUrinary Resource

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is a consortium of laboratories working to provide the scientific and medical community with gene expression data and tools to facilitate research (see "www.gudmap.org":http://www.gudmap.org). The data provided by GUDMAP includes large _in situ_ hybridization screens (wholemount and section) and expression microarray analysis of components of the developing mouse urogenital system (including laser-captured material and FACS-isolated cells from transgenic reporter mice). In addition, a high-resolution anatomy ontology has been developed by members of the GUDMAP consortium to describe the subcompartments of the developing murine genitourinary tract. 

The GUDMAP Database Development Team and Editorial Office - both based in Edinburgh - function to ensure submission, curation, storage and presentation of the data submitted by the GUDMAP consortium. Our collective aim is twofold: 1) to simplify the process of submission so that data is publically available as soon as it is produced; and 2) to organize this information in a database and ensure that the online interface is continuously available and easy to use. Thus far, we have developed a range of tools that help both the submitter and the end user. These include: an online annotation tool that simplifies _in situ_ data submission through an ontology-based graphical user interface; a database interface that allows users to browse and query expression data, and to filter data by organ system; a heat-map display of microarray data and analyses. Furthermore, the Edinburgh team has developed a GUDMAP Disease Database that queries associations between genes, genitourinary diseases, and renal/urinary and reproductive phenotypes. In collaboration with GUDMAP consortium members at the CCHMC (Cincinnati Children's Hospital Medical Center), the Disease Database is being extended to include mammalian phenotypes mapped to OMIM entries. 

By virtue of its impressive dataset and its ease of use we hope that the GUDMAP Website will continue to serve as a powerful resource for biologists, clinicians and bioinformaticians with an interest in the urogenital system

Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position

We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league), compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using Chi-square and odds ratio (OR) statistics. Correction of p-values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared to forwards (24.8%; P=0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ2=6.672, P=0.04; OR=1.60) and forwards (47.5%; χ2=11.768, P=0.01; OR=2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intra-sport positional differences exist, instead of combining several sports with varied demands and athlete characteristics