Updated recommendations for HER2 testing in the UK

This paper serves to update previously published guidance on rationale and methodology for HER2 laboratory testing following the recommendation for the use of HER2 targeted treatment in the management of advanced breast cancer in the UK. Emphasis is placed on the standardisation of methodology and assessment and strategies to achieve high quality performance. A two phase testing algorithm based on first line immunocytochemistry evaluation and second line fluorescence in situ hybridisation assessment of borderline cases is recommended. To ensure maintenance of expertise, an annual caseload volume of at least 250 cases is recommended for laboratories providing a testing service

Prescribing trends of gabapentin, pregabalin and oxycodone; a secondary analysis of primary care prescribing patterns in England

Background The risk of iatrogenic harm from prescription drug use, misuse and abuse of drugs such as gabapentin, pregabalin and oxycodone is substantial. In recent years, deaths associated with these drugs in England have increased. Aims To characterise general practice prescribing trends for gabapentin, pregabalin and oxycodone – termed dependence forming medicines (DFM) – in England and describe potential drivers of unwarranted variation. Design and Setting This study is a retrospective secondary analysis of open source, publicly available government data from various sources pertaining to primary care demographics and prescriptions. Methods This study used five consecutive years (April 2013 – March 2018) of aggregate data to investigate longitudinal trends of prescribing and variation in prescribing trends at practice and clinical commissioning group (CCG) level. Results Annual prescriptions of gabapentin, pregabalin and oxycodone have increased each year over the period. Variation in prescribing trends were associated with GP practice deprivation quintile, where the most deprived GP practices prescribe 313% (p<0.001) and 238% (p<0.001) greater volumes of gabapentin and pregabalin per person than practices in the least deprived quintile. The highest prescribing CCGs of each of these drugs were predominantly in northern and eastern regions of England. Conclusions Substantial increases in gabapentin, pregabalin and oxycodone prescriptions are concerning and will increase iatrogenic harm from drug-related morbidity and mortality. More research is needed to understand the large variation in prescribing between general practices; and to develop and implement interventions to reduce unwarranted variation and increase the appropriateness of prescribing of these drugs

An observational study to examine how Cumulative Impact Zones influence alcohol availability from different types of licensed outlets in an inner London Borough

OBJECTIVES: Cumulative Impact Zones (CIZs) are a widely implemented local policy intended to restrict alcohol availability in areas proliferated with licensed outlets. Limited previous research has questioned their effectiveness and suggested they may play a more nuanced role in shaping local alcohol environments. This study evaluates the association between CIZ implementation and the number of licence applications made and the number issued, relative to a control region. DESIGN: A quantitative observational study. SETTING: The inner London Borough of Southwark, which currently enforces three CIZs. POPULATION: Licence applications received by Southwark Council’s Licensing Authority between 1 April 2006 and 31 March 2017 (N = 1254). INTERVENTIONS: CIZ implementation. PRIMARY OUTCOME MEASURES: Five outlet types were categorised and evaluated: Drinking Establishments, Eateries, Takeaways, Off Sales, and Other Outlets. Primary outcome measures were the number of applications received and the number of licences issued. These were analysed using Poisson regression of counts over time. RESULTS: Across all CIZs, implementation was associated with greater increases in the number of eateries in CIZ regions (IRR = 1.58, 95% CI: 1.02 – 2.52, P = 0.04) and number of takeaway venues (IRR = 3.89, 95% CI: 1.32 – 11.49, P = 0.01), relative to the control area. No discernible association was found for the remaining outlet types. Disaggregating by area indicated a 10-fold relative increase in the number of new eateries in Peckham CIZ (IRR = 10.38, 95% CI: 1.39 – 77.66, P = 0.02) and a four-fold relative increase in the number of newly licensed takeaways in Bankside CIZ (IRR = 4.38, 95% CI: 1.20 – 15.91, P = 0.03). CONCLUSIONS: Cumulative Impact Zones may be useful as policy levers to shape local alcohol environments to support the licensing goals of specific geographical areas and diversify the night-time economy

Risk factors associated with knife-crime in United Kingdom among young people aged 10-24 years: a systematic review

BACKGROUND: Since 2013, the number of violent crimes and offences by sharp instruments have increased continually, following a previous decrease, with majority of cases occurring among young people and in London. There is limited understanding surrounding the drivers influencing this change in trends, with mostly American-based research identifying risk factors. METHODS: The aim of this review is to identify and synthesise evidence from a range of literature to identify risk factors associated with weapon-related crime, for young people (aged 10-24 years) within the UK. A search strategy was generated to conduct a systematic search of published and grey literature within four databases (EMBASE, Medline, PsycINFO, and OpenGrey), identifying papers within a UK-context. Abstracts and full texts were screened by two independent reviewers to assess eligibility for inclusion, namely study focus in line with the objectives of the review. Weight of Evidence approach was utilised to assess paper quality, resulting in inclusion of 16 papers. Thematic analysis was conducted for studies to identity and categorise risk factors according to the WHO ecological model. RESULTS: No association was found between gender or ethnicity and youth violence, contrasting current understanding shown within media. Multiple research papers identified adverse childhood experiences and poor mental health as positively associated with youth and gang violence. It was suggested that community and societal risk factors, such as discrimination and economic inequality, were frequently linked to youth violence. A small number of studies were included within the review as this is a growing field of research, which may have led to a constrained number of risk factors identified. Due to heterogeneity of studies, a meta-analysis could not be conducted. As many studies displayed positive results, publication bias may be present. CONCLUSIONS: Several risk factors were identified, with evidence currently heterogeneous with minimal high-quality studies. However, findings highlight key areas for future research, including the link between poor mental health and knife-crime, and the trajectory into gangs. Risk factors should help identify high-risk individuals, targeting them within mitigation strategies to prevent involvement within crime. This should contribute to efforts aimed at reducing the rising crime rates within UK. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42019138545 . Registered at PROSPSERO: 16/08/2019

How to find an attractive solution to the liar paradox

The general thesis of this paper is that metasemantic theories can play a central role in determining the correct solution to the liar paradox. I argue for the thesis by providing a specific example. I show how Lewis’s reference-magnetic metasemantic theory may decide between two of the most influential solutions to the liar paradox: Kripke’s minimal fixed point theory of truth and Gupta and Belnap’s revision theory of truth. In particular, I suggest that Lewis’s metasemantic theory favours Kripke’s solution to the paradox over Gupta and Belnap’s. I then sketch how other standard criteria for assessing solutions to the liar paradox, such as whether a solution faces a so-called revenge paradox, fit into this picture. While the discussion of the specific example is itself important, the underlying lesson is that we have an unused strategy for resolving one of the hardest problems in philosophy

From scientific obscurity to conservation priority: research on angler catch rates is the catalyst for saving the hump-backed mahseer Tor remadevii from extinction

1. The mahseer (Tor spp.) fishes of South and Southeast Asia are iconic megafaunal species that are highly valued by recreational anglers. Knowledge on their populations is limited due to the challenges associated with sampling these large bodied fishes (>50kg) in remote monsoonal rivers. Despite its global iconic status among recreational anglers, the hump-backed mahseer of South India’s River Cauvery lacked a valid scientific name and was on a trajectory towards extinction until its rapidly declining population status was established by analyses of angler catch records. 2. Angling records from 1998 to 2012 revealed that mahseer catch rates had increased in the period. The resulting publication in Aquatic Conservation (AQC) highlighted the positive role of catch-and-release angling in providing information on data-poor species. However, further analyses revealed these catches comprised of not one but two distinct phenotypes. Prior to 1993, all mahseer captured were hump-backed; since then, a blue-fin phenotype appeared in catches and subsequently dominated them. These results triggered further studies that revealed the hump-backed mahseer was the endemic Tor remadevii and the blue-fin was the invasive Tor khudree that had been introduced in 1976 and then stocked periodically from hatcheries. 3. The initial AQC publication successfully demonstrated the high value of organised angling as a monitoring tool for data-poor fishes and its application to assessing the temporal population patterns of large bodied fishes in monsoonal rivers. It was also the catalyst for initiating subsequent studies on T. remadevii that, in entirety, enabled its recent assessment as ‘Critically Endangered’ on the IUCN Red List. In the absence of the AQC paper, and the subsequent studies it triggered, it is highly probable that the species would have remained on a trajectory towards rapid extinction. Instead, the first major steps to safeguarding its future have been taken