TY - JOUR
AB - These important subjects have full free online access. In addition, as usual, the Bulletin has a section to celebrate its amazing archive (see end of ‘In this Issue’). The British Medical Bulletin (BMB) has been further developing its website and has a fascinating section on the Nobel Prize winners who wrote for the Bulletin and went on to win the accolade. The first free access review is: Things fall apart: the British health crisis 2010–2020 (pages 4) by Hiam, Dorling and McKee from the University of Oxford, UK. They state that a very large number of studies have reported a stalling of health improvements in the UK since 2010. There has been a dramatic slowdown in life expectancy and diverging trends in infant mortality in the UK as a whole and England and Wales, respectively. Many commentators are loath to describe the falls in life expectancy as actual falls or to ascribe blame to the political situation in the UK. The UK may have become a sentinel state within Europe, which illustrates the adverse effects of political disorganisation and disarray. The excuses politicians used as they tried to avoid responsibility for the multiple crises and their effects need to be better understood. Did politicians mislead or did they simply not understand? The second chosen free-to-view review is entitled Targeted biologic therapy for asthma (pages 16) by Hynes and Pavord from the University of Oxford, UK. They say that asthma is a common and potentially serious condition affecting 300 million people worldwide. With recent advances, it has become clear that asthma is a heterogeneous condition with multiple different underlying pathways. Understanding the different subtypes will be key to giving us the ability to intervene in a targeted way to personalise care for patients with asthma. The most widely studied of these subtypes has an increasing number of biologic therapies available. It is currently unclear which of the available biologics provides superior efficacy. It is also unclear how to select which biologic for which patient. It would be good to see further analyses of available biologics to allow us to predict responders from non-responders in advance of administering therapy. In the rest of the Bulletin, the third review is Challenges in molecular diagnosis of X-linked intellectual disability (ID)(pages 36) by De Luca, Race, Keldermans, Bauters and Van Esch from University Hospitals, Leuven, Belgium. They say that intellectual disability affects 1–3% of the Western population and is heterogeneous in origin. Mutations in X-linked genes represent 5–10% of ID in males. Females are usually non-affected or mildly affected carriers and, in a few rare cases, the only gender affected. Array comparative genome hybridization (aCGH) and next generation sequencing (NGS) have dramatically changed the nature of human genome analysis, leading to the identification of new syndromes and disease-causing genes. The main challenge in the era of NGS is filtering and interpretation of the data generated by the analysis of a single individual. In X-linked cases, assessing pathogenicity is particularly challenging. The fourth review is entitled The role of the immune system in tendon healing (pages 49) by Chisari, Rehak, Khan and Maffulli from University of Catania, Italy; Athena Biomedical Innovations, Florence, Italy; University of Cambridge, UK; Ospedale San Giovanni, Salerno, Italy; and the London School of Medicine and Keele University School of Medicine, UK. They say that the role of the immune system in tendon healing relies on polymorphonucleocytes, mast cells, macrophages and lymphocytes, the ‘immune cells’ and their cytokines production. This systematic review aims to report on how the immune system affects tendon healing. Macrophages are major actors in the promotion of proper wound healing as well as the resolution of inflammation in response to pathogenic challenge or tissue damage. The immune cells secrete cytokines involving both pro-inflammatory and anti-inflammatory factors, which could affect both healing and macrophage polarisation. A dysregulation of the immune response can ultimately lead to a failed healing response. The fifth review is entitled Understanding the genetic basis of congenital insensitivity to pain (pages 65) by Drissi, Woods and Woods from the University of Cambridge and University of Keele, UK. They say that congenital insensitivity to pain (CIP) is caused by extremely rare Mendelian genetic disorders. CIP individuals demonstrate the unexpectedly severe consequences of painlessness. Whilst only a small number of causative conditions and genes are known, most have led to profound insights into human nociception. CIP gene discovery is catalysing the manufacture of completely new classes of analgesics. There are further Mendelian causes of painlessness to be discovered. It is not known why all CIP phenotypes involve a complete loss of all types of nociception. The sixth review is entitled Therapeutic potential of microRNA in tendon injuries (pages 79) by Giordano, Della Porta, Peretti and Maffulli from the University of Salerno, Italy; University of Milan, Italy; Istituto Ortopedico Galeazzi, Milan, Italy; and Barts and the London School of Medicine and Keele University, UK. They state that the regulatory role of microRNA (miRNA) in several conditions has been studied, but their function in tendon healing remains elusive. This review summarises how miRNAs are related to the pathogenesis of tendon injuries and highlights their clinical potential, focusing on the issues related to their delivery for clinical purposes. The mechanism of repair of tendon injuries is probably mediated by resident tenocytes. These maintain a fine equilibrium between anabolic and catabolic events of the extracellular matrix. Specific miRNAs regulate cytokine expression and orchestrate proliferation and differentiation of stromal cell lines involved in the composition of the extracellular matrix. The seventh review is Obeticholic Acid (OCA)—a new therapy in primary biliary cholangitis (PBC) and non-alcoholic steatohepatitis (NASH) (pages 95) by Chapman and Lynch from the University of Oxford, UK, the University of Adelaide and Adelaide Local Health Network, Australia. They state that OCA is a semi-synthetic hydrophobic bile acid analogue, which is highly selective agonist of farnesoid X receptor (FXR), a key nuclear bile acid receptor, which induces expression of gut-derived hormones. The resulting beneficial effects of OCA on glucose and lipid metabolism and hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and non-alcoholic steatohepatitis (NASH). In recent clinical trials, OCA has been shown encouraging results by improving liver blood tests and reducing liver fibrosis with no worsening of NASH. The main side effects of OCA treatment in both PBC and NASH is that of dose-dependent pruritis, which can lead to treatment discontinuation in ~1–10% of patients. OCA-treated patients may also exhibit (reversible) alterations in serum lipid levels. The eighth review is The epidemiology of osteoporosis (pages 105) by Clynes, Curtis, Fuggle, Dennison and Cooper from the University of Southampton, UK. They state that with a worldwide ageing population, the importance of the prevention and management of osteoporotic fragility fractures is increasing over time. In this review, we discuss in detail the epidemiology of fragility fractures, how this is shaped by pharmacological interventions and how novel screening programmes can reduce the clinical and economic burden of osteoporotic fractures. The economic burden of osteoporosis-related fracture is significant, costing approximately $17.9 billion and £4 billion per annum in the USA and UK. Despite advances in osteoporosis screening, a minority of men and women at high fracture risk worldwide receive treatment. The economic and societal burden caused by osteoporosis is a clear motivation for improving the screening and management of osteoporosis worldwide. From the Archive The British Medical Bulletin (BMB) has an extensive archive dating back to 1943. Each quarter, the journal is publishing a selected paper from that archive. This quarter, we have a piece on Some recent observations on the inheritance of blood groups by R. R. Race. He, with other researchers, was working out the details of blood groups. Curiously, much of the work had a eugenics tinge to it; indeed much of his work and that of his colleague G. L. Taylor was published in the Annals of Eugenics. At the end of the papers they produced, there is often a small eugenics point, which these days we would find distasteful. Thus at the end of the cited article: ‘The Rh-positive babies of only about 5% of Rh-negative women are affected with haemolytic disease. Such women may possess highly permeable placentae, and if the abnormal permeability was due to a gene and the gene could be recognised, then there would be a strong case for dis-couraging a mating which involved. (i) an Rh-negative woman and (ii) this gene for placental permeability and (iii) an Rh-positive man.’ The original link is: https://academic.oup.com/bmb/article/2/8-9/165/286094. You can access the collected articles more easily and more fully by visiting the ‘Highlights from the BMB Archive’ collection (http://bit.ly/2nTsFIH)’. Enjoy! NJV March 2020 © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Things fall apart: the British health crisis 2010–2020 and targeted biological therapy for asthma
JF - British Medical Bulletin
DO - 10.1093/bmb/ldaa007
DA - 2020-05-15
UR - https://www.deepdyve.com/lp/oxford-university-press/things-fall-apart-the-british-health-crisis-2010-2020-and-targeted-u5kbTsuhjs
SP - 1
EP - 3
VL - 133
IS - 1
DP - DeepDyve
ER -