Acute kidney injury: an acceptable risk of treatment with renin-angiotensin system blockade in primary care?

Background: Use of renin-angiotensin system (RAS) blockade has become increasingly widespread driven by evidence-based guidance. There is concern about the role of these agents in the genesis of avoidable acute kidney injury (AKI). Objectives: To investigate the association between AKI and use of RAS blockade. Design: Multilevel hierarchical analysis of a large cohort of patients registered with UK general practitioners. Setting: Primary care practices in East and West Kent, United Kingdom. Patients: 244,715 patients from 27 practices. Measurements: Demographic, clinical, biochemical and prescription data. Methods: Analyses of data acquired between 02/3/2004 and 17/04/2012 using multilevel logistic regression to determine the relationship between AKI and use of RAS blockade; further analysed by indication for treatment with RAS blockade. Results: Sufficient serum creatinine data were available to define AKI in 63,735 patients with 208,275 blood test instances. In 95,569 instances the patient was prescribed a RAS antagonist of which 5.4% fulfilled criteria for AKI. The unadjusted odds ratio (OR) for AKI in those prescribed RAS blockade was 1.93 (1.81-2.06, 95%CI) falling to 1.11 (1.02-1.20, 95%CI) when adjusted for age, gender, co-morbidity, GFR category, proteinuria, systolic blood pressure and diuretic therapy. In patients with an evidence-based indication there was no difference in absolute risk of AKI. However, prescription of RAS blockade in the absence of indication appeared to be associated with greater risk of AKI. When analysis was repeated with AKIN2/AKIN3 as the outcome, although risk of AKI remained significant when unadjusted (OR 1.73, 95%CI 1.42-2.11, p<0.001), after full adjustment there was no increased risk (OR 0.83, 95%CI 0.63-1.09) in those taking RAS antagonists. However, when analysed by indication AKIN2/AKIN3 was significantly more likely in those prescribed RAS antagonists without indication (OR 2.04, 95%CI 1.41-2.94, p<0.001). Limitations: Observational database study. No information concerning hospitalisation. Prescribing assumptions and potential inaccurate coding. Potential survival bias; patients surviving longer will contribute more data. Conclusions: Use of RAS antagonists increased the risk of AKI, independent of common confounding variables. After correction for confounders the risk fell away and became non-significant for moderate and severe AKI. However, where there was no evidence-based indication for RAS antagonists the risk of AKI, whether mild, moderate or severe, remained greater

Conceptualising sustainability in UK urban Regeneration: a discursive Formation

Despite the wide usage and popular appeal of the concept of sustainability in UK policy, it does not appear to have challenged the status quo in urban regeneration because policy is not leading in its conceptualisation and therefore implementation. This paper investigates how sustainability has been conceptualised in a case-based research study of the regeneration of Eastside in Birmingham, UK, through policy and other documents, and finds that conceptualisations of sustainability are fundamentally limited. The conceptualisation of sustainability operating within urban regeneration schemes should powerfully shape how they make manifest (or do not) the principles of sustainable development. Documents guide, but people implement regeneration—and the disparate conceptualisations of stakeholders demonstrate even less coherence than policy. The actions towards achieving sustainability have become a policy ‘fix’ in Eastside: a necessary feature of urban policy discourse that is limited to solutions within market-based constraints

Clarifying Differences Between Reading Skills and Reading Strategies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88049/1/RT.61.5.1.pd

Analysing and Recommending Options for Maintaining Universal Coverage with Long-Lasting Insecticidal Nets: The Case of Tanzania in 2011.

Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or "Keep-Up" distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of$449 million USD and ensure continuous coverage. The cost of each strategy was largely driven by the number of LLINs delivered. The most cost-efficient strategy to maintain universal coverage is one that best optimizes the numbers of LLINs needed over time. A school-based approach using vouchers targeting all students in Standards 1, 3, 5, 7 and Forms 1 and 2 in combination with the TNVS appears to meet best the criteria of effectiveness, equity and efficiency

Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

Background: Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy ( SNAP) trial will investigate whether or not nicotine replacement therapy ( NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design: Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date ( defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion: This trial is designed to ascertain whether or not standard doses of NRT ( as transdermal patches) are effective and safe when used for smoking cessation during pregnancy

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation

Background: Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA®, AbbVie, Maidenhead, UK), etanercept (Enbrel®, Pfizer, New York, NY, USA) and ustekinumab (STELARA®, Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children. Objective: To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people. Data sources: Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation. Review methods: Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway. Results: Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks’ follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short-term adverse events; however, the possibility of rare events cannot be excluded. The majority of the incremental cost-effectiveness ratios for the use of biologics in children and young people exceeded NICE’s usual threshold for cost-effectiveness and were reduced significantly only when combined assumptions that align with those made in the management of psoriasis in adults were adopted. Limitations: The clinical evidence base for short- and long-term outcomes was limited in terms of total participant numbers, length of follow-up and the absence of young children. Conclusions: The paucity of clinical and economic evidence to inform the cost-effectiveness of biological treatments in children and young people imposed a number of strong assumptions and uncertainties. Health-related quality-of-life (HRQoL) gains associated with treatment and the number of hospitalisations in children and young people are areas of considerable uncertainty. The findings suggest that biological treatments may not be cost-effective for the management of psoriasis in children and young people at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year, unless a number of strong assumptions about HRQoL and the costs of BSC are combined. Registry data on biological treatments would help determine safety, patterns of treatment switching, impact on comorbidities and long-term withdrawal rates. Further research is also needed into the resource use and costs associated with BSC. Adequately powered randomised controlled trials (including comparisons against placebo) could substantially reduce the uncertainty surrounding the effectiveness of biological treatments in biologic-experienced populations of children and young people, particularly in younger children. Such trials should establish the impact of biological therapies on HRQoL in this population, ideally by collecting direct estimates of EuroQol-5 Dimensions for Youth (EQ-5D-Y) utilities. Study registration: This study is registered as PROSPERO CRD42016039494. Funding: The National Institute for Health Research Health Technology Assessment programme

Environmental impact assessments of the Three Gorges Project in China: issues and interventions

The paper takes China's authoritative Environmental Impact Statement for the Yangzi (Yangtze) Three Gorges Project (TGP) in 1992 as a benchmark against which to evaluate emerging major environmental outcomes since the initial impoundment of the Three Gorges reservoir in 2003. The paper particularly examines five crucial environmental aspects and associated causal factors. The five domains include human resettlement and the carrying capacity of local environments (especially land), water quality, reservoir sedimentation and downstream riverbed erosion, soil erosion, and seismic activity and geological hazards. Lessons from the environmental impact assessments of the TGP are: (1) hydro project planning needs to take place at a broader scale, and a strategic environmental assessment at a broader scale is necessary in advance of individual environmental impact assessments; (2) national policy and planning adjustments need to react quickly to the impact changes of large projects; (3) long-term environmental monitoring systems and joint operations with other large projects in the upstream areas of a river basin should be established, and the cross-impacts of climate change on projects and possible impacts of projects on regional or local climate considered. © 2013 Elsevier B.V.Xibao Xu, Yan Tan, Guishan Yan

Designing location based learning experiences for people with intellectual disabilities and additional sensory impairments

The research reported here is part of a larger project which seeks to combine serious games (or games based learning) with location based services to help people with intellectual disability and additional sensory impairments to develop work based skills. Specifically this paper reports on where these approaches are combined to scaffold the learning of new routes and ultimately independent travel to new work and educational opportunities. A phased development methodology is applied in a user sensitive manner, to ensure that user feedback drives the ongoing development process. Methods to structure this include group feedback on conceptual storyboards, expert review of prototypes using usability heuristics relating to the main system goals, and finally co-discovery methods with student pairs exploring all three modes of the system in real world contexts. Aspects of developmental and cognitive psychological theories are also reviewed and it is suggested that combining games based learning approaches with location based services is an appropriate combination of technologies for an application specifically designed to scaffold route learning for this target audience

The digital divide: Patterns, policy and scenarios for connecting the ‘final few’ in rural communities across Great Britain

The Internet can bestow significant benefits upon those who use it. The prima facie case for an urban-rural digital divide is widely acknowledged, but detailed accounts of the spatial patterns of digital communications infrastructure are rarely reported. In this paper we present original analysis of data published by the UK telecommunications regulator, Ofcom, and identify and reflect on the entrenched nature of the urban-rural digital divide in Great Britain. Drawing upon illustrative case vignettes we demonstrate the implications of digital exclusion for personal and business lives in rural, and in particular remote rural, areas. The ability of the current UK policy context to effectively address the urban-rural digital divide is reviewed and scenarios for improving digital connectivity amongst the ‘final few’, including community-led broadband, satellite broadband and mobile broadband, are considered. A call is made for digital future proofing in telecommunications policy, without which the already faster urban areas will get ‘faster, fastest’ leaving rural areas behind and an increasingly entrenched urban-rural divide

Methane emissions from oil and gas transport facilities – exploring innovative ways to mitigate environmental consequences

Climate change impacts are increasingly becoming more evident e.g. through heavy rainfall episodes and subsequent flooding. Methane is a significant greenhouse gas that has been linked to these impacts and the oil and gas industry is a major source of anthropogenic methane emission. Recent studies have suggested that the tropical region hold some unexpectedly high methane concentration and that the recent changes in the global methane burden are poorly understood. To address this research gap, we present a first effort to quantify methane emissions from one of the most vulnerable oil and gas infrastructures in Nigeria (a tropical country). A combination of the Intergovernmental Panel on Climate Change tier-1 approach and an adapted Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation model was used to estimate methane emissions from the system 2C transport pipeline. We then tested the hypothesis of no significant change in methane emissions trend from the pipeline using the between group t-test inferential analysis. Key findings include: (a) a crude oil throughput of 55,143 to 1,500,500 barrels (8767 to 238,561 m3) emitted methane ranging from 0.04734 to 1.288MT (± 50 to 200%) respectively, and (b) surprisingly, methane emissions along the system 2C pipeline seem to have continued without significant change between 2005, and 2008 to 2012 despite the low crude oil throughput in 2009. This indicates the likelihood of continuous but rising methane emissions from the pipeline network over a six-year period; and only further research can ascertain if similar trend can be observed elsewhere in the tropical region. These findings are unique and contribute to the current global debate on methane emissions from the largely unmonitored tropical region. Therefore, we recommend that stakeholders should set up a study plan for the identification and continuous monitoring of methane emissions from the key oil and gas infrastructure and explore opportunities for geoengineering applications as part of climate change mitigation. Coordinated engagement in international schemes such as the Natural Gas STAR program, Climate and Clean Air Coalition, Global Methane Initiative amongst others would promote strategic and measurable methane reduction plans in Nigeria and other countries within/outside the tropical region