Feasibility and evaluation of an emergency department‐based general practitioner streaming and treatment service

Rationale Offering a primary care service that can provide good quality primary care at emergency departments may reduce pressure on usual emergency department (ED) services. Aims and Objectives To evaluate the acceptability, satisfaction, and potential impacts of a co-located primary care service at an emergency department. Methods This is a prospective feasibility study and service evaluation comprising a narrative summary of activity, satisfaction, well-being, and safety, and comparisons of wait times for ED services by patient category (‘minor’, ‘majors’, ‘paediatric’ or ‘resus’) before and during the service operation. Patients and staff were asked using semistructured interview topic guides about service perception, well-being, representation within 48 h, safety concerns, and/or satisfaction. Wait times for patient categories in usual ED care service were in secondary care electronic records. Pathway changes were captured under primary care electronic records. Results Approximately 96% of general practitioner streaming and treatment (GPST) patients were seen within 1 h. There was a statistically significant reduction in ED patients with minor injuries or illnesses waiting >4 h for admission or discharge ‘breaches’ during the 3 months that GPST was operating compared with the previous 3 months (p ≤ 0.005). Wait times for other ED services did not significantly improve. A total of 769 walk-in patients received GPST consultation and 661 (86%) needed no further ED intervention. Fast discharge was a major determinant of patient satisfaction. No staff expressed dissatisfaction, but some suggested possible improvements in eligibility criteria and built environment design features. Conclusion Provision of GPST correlated with shorter waits for discharge from ED. Patient and staff experiences of GPST were positive

Controlling the Functionality of Amphiphilic Block Copolymers Self-assembled into Bicontinuous Nanospheres

Amphiphilic block copolymers (BCPs) can self-assemble into a variety of different aggregates in solution. Simple morphologies include spherical micelles, cylindrical micelles and vesicles (polymersomes). More complex aggregate structures include bicontinuous nanospheres which this thesis will focus on. The work in this thesis looks at thermoresponsive bicontinuous nanospheres which has an application for drug delivery. Previously, research has demonstrated that bicontinuous nanospheres can be made from PEO-b-PODMA (poly(ethylene oxide)-block-poly(octadecyl methacrylate)) & PEO-b-PDSMA (poly(ethylene oxide)-block-poly(docosyl methacrylate)). The bicontinuous nanospheres formed are semi-crystalline due to the methacrylate block which gives a melting transition temperature (Tm). PEO-b-PODMA has a Tm of 21.8°C and PEO-b-PDSMA has a Tm of 41.3°C. This previous work showed that by copolymerising and varying wt% ratios of PODMA:DSMA that there was manipulation of the Tm which was conducted using differential scanning calorimetry (DSC). The work outlined in this thesis repeated this work but instead of copolymerising, blending block copolymers in the same varied wt% ratios of PODMA:DSMA was carried out. This was to assess whether blending polymers could manipulate the Tm in the same way. DSC analysis suggested partial mixing occurred when PEO-b-PODMA & PEO-b-PDSMA were blended. In the hopes to achieve full blending, a series of nucleobase monomers were made which contained adenine and thymine. Adenine and thymine are base pairs where hydrogen bonding occurs between the two bases. These nucleobase monomers were then added in ATRP reactions to make random copolymers of PODMA-co-PVBT and PDSMA-co-PVBA and block copolymers of PEO-b-PODMA-co-PVBT and PEO-b-PDSMA-co-PVBA. It was the hope of the strong hydrogen bonding affect that occurs between adenine and thymine, would be enough to encourage full mixing of the polymer blends. The block copolymers were lastly self-assembled to see if bicontinuous nanospheres still formed after the nucleobases had been incorporated into the random and block copolymers

Synthesis, characterisation and analysis of metal-organic frameworks for sustainable catalysis applications

A range of metal-organic frameworks (MOFs) have been synthesised and characterised by a variety of techniques, primarily including powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), UV-Vis and Scanning Electron Microscopy (SEM). Some of these MOFs have been investigated for applications related to CO2 capture and catalysis. A mixed-metal MOF, MUV-10, comprised of titanium in combination with Ca or Mn, is thoroughly investigated with the aim of making modifications, including the substitution of some Ti for Sn. Synchrotron X-ray absorption spectroscopy confirmed the successful incorporation of Sn(IV) into the mixed-metal MOFs. Gas adsorption studies were also completed and a brief investigation into the modification of the organic linker used in the material, with effects on the band gap of the material discussed. The modified MUV-10 MOFs have been extensively analysed and their activity tested in the photoreduction of carbon dioxide, the reduction of carbon dioxide to cyclic carbonates using epoxides and in the conversion of glucose to 5-hydroxymethylfurfural (5-HMF). For the formation of cyclic carbonates using epoxides and carbon dioxide, MUV-10 offered excellent conversion, recyclability, and stability. For the conversion of glucose, when small quantities of HCl were used, MUV-10 demonstrated a greater production of 5-HMF compared to the UiO-66 reference material, with enhanced performance for MUV-10 substituted with Sn. The synthesis of novel Ti MOFs has been attempted, and although none were produced in a form for structure solution, some promising materials were identified for future study. Similar studies on the synthesis of Sn(IV) MOFs, not yet known in the literature, also proved not to form large enough crystals for structure solution, although a new anionic Sn(II) coordination polymer based on the chelidamate ligand was crystallised

Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation.

Dexamethasone treatment of F0 pregnant rodents alters F1 placental function and adult cardiometabolic phenotype. The adult phenotype is transmitted to the F2 generation without further intervention, but whether F2 placental function is altered by F0 dexamethasone treatment remains unknown. In the present study, F0 mice were untreated or received dexamethasone (0.2µgg(-1)day(-1), s.c.) over Days 11-15 or 14-18 of pregnancy (term Day 21). Depending on the period of F0 dexamethasone treatment, F1 offspring were lighter at birth or grew more slowly until weaning (P<0.05). Glucose tolerance (1gkg(-1), i.p.) of adult F1 males was abnormal. Mating F1 males exposed prenatally to dexamethasone with untreated females had no effect on F2 placental function on Day 19 of pregnancy. In contrast, when F1 females were mated with untreated males, F2 placental clearance of the amino acid analogue (14)C-methylaminoisobutyric acid was increased by 75% on Day 19 specifically in dams prenatally exposed to dexamethasone on Days 14-18 (P<0.05). Maternal plasma corticosterone was also increased, but F2 placental Slc38a4 expression was decreased in these dams (P<0.05). F0 dexamethasone treatment had no effect on F2 fetal or placental weights, regardless of lineage. Therefore, the effects of F0 dexamethasone exposure are transmitted intergenerationally to the F2 placenta via the maternal, but not paternal, line.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1071/RD14285

PPI and Scoping Review for GP at Door of Accident and Emergency services

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Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in female mice.

Phosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when female Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a possible modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that female mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.The work was also supported by Diabetes UK and the MRC [G1002610]. VP held an Arthur and Sadie Pethybridge PhD Studentship from Diabetes UK. The CIMR microscopy core facility is supported by a Wellcome Trust Strategic Award [100140] and a Wellcome Trust equipment grant [093026]

Testing for SARS-CoV-2 infection in care home residents and staff in English care homes: A service evaluation

Context COVID-19 is especially dangerous to older adults living in residential care. Objective To evaluate the usefulness of a nurse-led Enhanced Care Home Team (ECHT) SARS-CoV-2 testing strategy to identify resident cases early, identify typical illness presentation residents, and correctly attribute cause of death in care home settings in Norfolk, UK. Method Residents and staff received nose and throat swab tests (7 April to 29 June 2020). Resident test results were linked with symptoms on days 0-14 after test and mortality to 13 July 2020. The data collected were used to evaluate service performance. Findings Residents (n=521) and staff (estimated n=340) in 44 care homes were tested in the ECHT service. SARS-CoV-2 positivity was identified in 103 residents in 14 homes and 49 staff in seven homes. Of 103 SARS-CoV-2+ residents, just 37 had what were understood to be typical COVID-19 symptom(s). Among 51 residents without symptoms when initially tested, 13 (25%) developed symptoms within 14 days. Many SARS-CoV-2+ residents lacked typical symptoms but presented rather as ‘generally unwell’ (n=16). Of 39 resident deaths during the monitoring period, 20 (51%) were initially attributed to SARS-CoV-2, all of whom tested SARS-CoV-2+. One deceased person not initially attributed to SARS-CoV-2 tested positive through a different monitoring programme. 9% of all staff tests were positive. Implications A locally designed and integrated joint nursing and social care team approach successfully identified asymptomatic and pre-symptomatic SARS-CoV-2+ residents and staff. Being ‘generally unwell’ was common amongst symptomatic residents and indicated SARS-CoV-2 infection in older people in the absence of more ‘typical’ symptoms. The service supported correct attribution of cause of death

Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma

Asthma patients who continue to experience symptoms despite being on regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta2-agonists (LABA) or anti-leukotrienes (LTRA) are two treatment options that could be considered as add-on therapy to ICS.ObjectivesWe compared the efficacy and safety profile of adding either daily LABA or LTRA in adults and children with asthma who remain symptomatic on ICS.Search strategyWe searched the Cochrane Airways Group Specialised Register (up to and including March 2010). We consulted reference lists of all included studies and contacted authors and pharmaceutical manufacturers for other published or unpublished studies.Selection criteriaWe included randomised controlled trials (RCTs) conducted in adults or children with recurrent asthma that was treated with ICS and where a fixed dose of a long-acting beta2-agonist or leukotriene agent was added for a minimum of 28 days.Data collection and analysisTwo authors independently assessed the risk of bias of included studies and extracted data. We sought unpublished data and further details of study design, where necessary.Main resultsWe included 17 RCTs (7032 participants), of which 16 recruited adults and adolescents (6850) and one recruited children aged 6 to 17 years (182). Participants demonstrated substantial reversibility to short-acting beta-agonist at baseline. The studies were at a low risk of bias. The risk of exacerbations requiring systemic corticosteroids was lower with the combination of LABA and ICS compared with LTRA and ICS, from 11% to 9% (RR 0.83, 95% CI 0.71 to 0.97; six studies, 5571 adults). The number needed to treat (NNT) with LABA compared to LTRA to prevent one exacerbation over 48 weeks was 38 (95% CI 22 to 244). The choice of LTRA did not significantly affect the results. The effect appeared stronger in the trials using a single device to administer ICS and LABA compared to those using two devices. In the absence of data from the paediatric trial and the clinical homogeneity of studies, we could not perform subgroup analyses. The addition to ICS of LABA compared to LTRA was associated with a statistically greater improvement from baseline in several of the secondary outcomes, including lung function, functional status measures and quality of life. Serious adverse events were more common with LABA than LTRA, although the estimate was imprecise (RR 1.35, 95% CI 1.00 to 1.82), and the NNT to harm for one additional patient to suffer a serious adverse event on LABA over 48 weeks was 78 (95% CI 33 to infinity). The risk of withdrawal for any reason in adults was significantly lower with LABA and ICS compared to LTRA and ICS (RR 0.84, 95% CI 0.74 to 0.96).Authors' conclusionsIn adults with asthma that is inadequately controlled on low doses of inhaled steroids and showing significant reversibility with beta2-agonists, LABA is superior to LTRA in reducing oral steroid treated exacerbations. Differences favouring LABA in lung function, functional status and quality of life scores are generally modest. There is some evidence of increased risk of SAEs with LABA. The findings support the use of a single inhaler for the delivery of LABA and inhaled corticosteroids. We are unable to draw conclusions about which treatment is better as add-on therapy for children.PLAIN LANGUAGE SUMMARYWhat are the effects of long-acting beta2-agonists compared with anti-leukotrienes when added to inhaled steroids?People who continue to experience asthma symptoms despite regularly taking inhaled corticosteroids are a challenge for management. It is not clear whether the addition of a long-acting beta2-agonist (LABA) such as formoterol or salmeterol would provide more benefit in comparison with an oral anti-leukotriene agent (LTRA), for example zafirlukast or montelukast.Seventeen trials (16 in adults and one in children) were included in this review and were of good quality. We found that the addition of a LABA provides significantly greater protection against exacerbations requiring oral steroids when compared with a LTRA for adults. Based on the results of our analyses, approximately 38 adults (with a range of between 22 and 244) would need to be treated with a LABA rather than a LTRA for 48 weeks to prevent one experiencing an exacerbation needing a course of oral steroids. The trial on children did not contribute data on the main outcome and therefore we could not draw any conclusions for children.LABAs also led to a greater improvement in lung function, improvement in symptoms, use of rescue medication, quality of life and symptoms compared to the use of LTRAs. The magnitude of the improvements was modest. Serious adverse events were more frequent with LABA than with LTRAs although this result was imprecise. Based on our analyses, around 78 people would need to be treated for 48 weeks with a LABA rather than a LTRA for one of them to experience a serious adverse event. However, due to the lack of precision around our result, the true number could be between 33 and infinity. There are currently insufficient data to draw any conclusions about the effects of these drugs in children

How to specify healthcare process improvements collaboratively using rapid, remote consensus-building: a framework and a case study of its application

Abstract: Background: Practical methods for facilitating process improvement are needed to support high quality, safe care. How best to specify (identify and define) process improvements – the changes that need to be made in a healthcare process – remains a key question. Methods for doing so collaboratively, rapidly and remotely offer much potential, but are under-developed. We propose an approach for engaging diverse stakeholders remotely in a consensus-building exercise to help specify improvements in a healthcare process, and we illustrate the approach in a case study. Methods: Organised in a five-step framework, our proposed approach is informed by a participatory ethos, crowdsourcing and consensus-building methods: (1) define scope and objective of the process improvement; (2) produce a draft or prototype of the proposed process improvement specification; (3) identify participant recruitment strategy; (4) design and conduct a remote consensus-building exercise; (5) produce a final specification of the process improvement in light of learning from the exercise. We tested the approach in a case study that sought to specify process improvements for the management of obstetric emergencies during the COVID-19 pandemic. We used a brief video showing a process for managing a post-partum haemorrhage in women with COVID-19 to elicit recommendations on how the process could be improved. Two Delphi rounds were then conducted to reach consensus. Results: We gathered views from 105 participants, with a background in maternity care (n = 36), infection prevention and control (n = 17), or human factors (n = 52). The participants initially generated 818 recommendations for how to improve the process illustrated in the video, which we synthesised into a set of 22 recommendations. The consensus-building exercise yielded a final set of 16 recommendations. These were used to inform the specification of process improvements for managing the obstetric emergency and develop supporting resources, including an updated video. Conclusions: The proposed methodological approach enabled the expertise and ingenuity of diverse stakeholders to be captured and mobilised to specify process improvements in an area of pressing service need. This approach has the potential to address current challenges in process improvement, but will require further evaluation