Barnabas J Gilbert

The role of amyloid β in the pathogenesis of Alzheimer's disease

The amyloid-β peptide (Aβ) is widely considered to be the major toxic agent in the pathogenesis of Alzheimers disease, a condition which afflicts approximately 36 million people worldwide. Despite a plethora of studies stretching back over two decades, identifying the toxic Aβ species has proved difficult. Debate has centred on the Aβ fibril and oligomer. Despite support from numerous experimental models, important questions linger regarding the role of the Aβ oligomer in particular. It is likely a huge array of oligomers, rather than a single species, which cause toxicity. Reappraisal of the role of the Aβ fibril points towards a dynamic relationship with the Aβ oligomer within an integrated system, as supported by evidence from microglia. However, some continue to doubt the pathological role of amyloid β, instead proposing a protective role. If the field is to progress, all Aβ oligomers should be characterised, the nomenclature revised and a consistent experimental protocol defined. For this to occur, collaboration will be required between major research groups and innovative analytical tools developed. Such action must surely be taken if amyloid-based therapeutic endeavour is to progress.

The influence of volume and experience on individual surgical performance: a systematic review.

OBJECTIVE To systematically review studies evaluating the influence of surgical experience on individual performance. BACKGROUND Experience, measured in case volume or years of practice, is recognized as a key driver of individual surgical performance, giving rise to a learning curve. However, this topic has not been reviewed at the cross-specialty level. METHODS MEDLINE, EMBASE, PsycINFO, AMED, and the Cochrane Database of Systematic Reviews were searched (from inception to February 2013). Two reviewers independently reviewed citations using predetermined inclusion and exclusion criteria. Ninety-one data points per study were extracted. RESULTS The search strategy yielded 6950 citations. Fifty-seven studies were eligible, including 1,061,913 cases and 35 procedure types, performed by 17,912 surgeons. Forty-five studies monitored case volume, and 6 studies measured experience as both case volume and years of practice. Of these 51 studies, 44 found that increased case volume was associated with significantly improved health outcomes. Several studies noted a plateau phase or maturation in the surgical learning curve. Acquisition of this phase was procedure specific and outcome specific, ranging from 25 to 750 procedures. Twelve studies assessed the impact of years of surgical practice, 11 of which found that increased years of experience was associated with significantly improved health outcomes. Two studies noted a plateau phase, where increases in years of experience were no longer associated with improvements in operative outcomes. Three studies identified performance deterioration after the plateau phase. CONCLUSIONS Increasing surgical case volume and years of practice are associated with improved performance, in a procedure-specific manner. Performance may deteriorate toward the end of a surgeons career.

Should trainee doctors use the developing world to gain clinical experience? The annual Varsity Medical Debate ¿ London, Friday 20th January, 2012

The 2012 Varsity Medical Debate between Oxford University and Cambridge University provided a stage for representatives from these famous institutions to debate the motion “This house believes that trainee doctors should be able to use the developing world to gain clinical experience.” This article brings together many of the arguments put forward during the debate, centring around three major points of contention: the potential intrinsic wrong of ‘using’ patients in developing countries; the effects on the elective participant; and the effects on the host community. The article goes on to critically appraise overseas elective programmes, offering a number of solutions that would help optimise their effectiveness in the developing world.

Should assisted dying be legalised

When an individual facing intractable pain is given an estimate of a few months to live, does hastening death become a viable and legitimate alternative for willing patients? Has the time come for physicians to do away with the traditional notion of healthcare as maintaining or improving physical and mental health, and instead accept their own limitations by facilitating death when requested? The Universities of Oxford and Cambridge held the 2013 Varsity Medical Debate on the motion “This House Would Legalise Assisted Dying”. This article summarises the key arguments developed over the course of the debate. We will explore how assisted dying can affect both the patient and doctor; the nature of consent and limits of autonomy; the effects on society; the viability of a proposed model; and, perhaps most importantly, the potential need for the practice within our current medico-legal framework.

Effects of economic crises on population health outcomes in Latin America, 1981-2010: an ecological study.

Objectives The relative health effects of changes in unemployment, inflation and gross domestic product (GDP) per capita on population health have not been assessed. We aimed to determine the effect of changes in these economic measures on mortality metrics across Latin America. Design Ecological study. Setting Latin America (21 countries), 1981–2010. Outcome measures Uses multivariate regression analysis to assess the effects of changes in unemployment, inflation and GDP per capita on 5 mortality indicators across 21 countries in Latin America, 1981–2010. Country-specific differences in healthcare infrastructure, population structure and population size were controlled for. Results Between 1981 and 2010, a 1% rise in unemployment was associated with statistically significant deteriorations (p<0.05) in 5 population health outcomes, with largest deteriorations in 1–5 years of age and male adult mortality rates (1.14 and 0.53 rises per 1000 deaths respectively). A 1% rise in inflation rate was associated with significant deteriorations (p<0.05) in 4 population health outcomes, with the largest deterioration in male adult mortality rate (0.0033 rise per 1000 deaths). Lag analysis showed that 5 years after rises in unemployment and inflation, significant deteriorations (p<0.05) occurred in 3 and 5 mortality metrics, respectively. A 1% rise in GDP per capita was associated with no significant deteriorations in population health outcomes either in the short or long term. β coefficient comparisons indicated that the effect of unemployment increases was substantially greater than that of changes in GDP per capita or inflation. Conclusions Rises in unemployment and inflation are associated with long-lasting deteriorations in several population health outcomes. Unemployment exerted much larger effects on health than inflation. In contrast, changes in GDP per capita had almost no association with the explored health outcomes. Contrary to neoclassical development economics, policymakers should prioritise amelioration of unemployment if population health outcomes are to be optimised.

Cancer cases diagnosed as emergencies may be fewer than reported

The news item highlighting survival after elective surgery for colorectal cancer reiterates dismay at the “stubbornly high proportion of patients who present as an emergency” (21% of cancers diagnosed between 1 April 2011 and 31 March 2012).1 2 Using data on cancers diagnosed during 2006-08,3 the current “Be Clear on Lung Cancer” campaign emphasises that “39% of lung cancer …

A systematic analysis of UK cancer research funding by gender of primary investigator

Objectives To categorically describe cancer research funding in the UK by gender of primary investigator (PIs). Design Systematic analysis of all open-access data. Methods Data about public and philanthropic cancer research funding awarded to UK institutions between 2000 and 2013 were obtained from several sources. Fold differences were used to compare total investment, award number, mean and median award value between male and female PIs. Mann-Whitney U tests were performed to determine statistically significant associations between PI gender and median grant value. Results Of the studies included in our analysis, 2890 (69%) grants with a total value of £1.82 billion (78%) were awarded to male PIs compared with 1296 (31%) grants with a total value of £512 million (22%) awarded to female PIs. Male PIs received 1.3 times the median award value of their female counterparts (P<0.001). These apparent absolute and relative differences largely persisted regardless of subanalyses. Conclusions We demonstrate substantial differences in cancer research investment awarded by gender. Female PIs clearly and consistently receive less funding than their male counterparts in terms of total investment, the number of funded awards, mean funding awarded and median funding awarded.