bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why do patients attend and what do they want from the consultation?
Authors: Spence Des 
Published: February 2020

Abstract
Contrary to traditional thinking and teaching, it is not illness that dictates the health-seeking behaviour of a population but the healthcare system itself, and—most importantly—our actions as healthcare professionals. A scourge affecting clinical practice in the developed world today is the medicalization of all interactions, accompanied by overinvestigation, overdiagnosis, and overtreatment. The medical profession retains its traditional duty, wherever possible, to diagnose disease and treat or cure illness appropriately, also to comfort the sick, irrespective of the ability to cure. At the same time, a long-held principle of medicine at all levels is to do no harm, while at the same time supporting the maintenance of health and protecting those who are well. This chapter explains how maintaining the balance between these apparent conflicting precepts is a scarce skill that needs to be taught by example during the education and training of the modern doctor.
Medical ethics
Authors: Parker Mike , Suleman Mehrunisha , Hope Tony 
Published: February 2020

Abstract
Medicine is both a scientific and a moral enterprise. It is as important to give reasons for the ethical aspects of clinical decisions as it is for the scientific aspects. The corollary of evidence-based medicine is reason-based ethics. Two concepts central to many ethical aspects of clinical practice are autonomy and best interests. Evidence-based medicine emphasizes the importance of critical assessment: interventions should be evaluated on the basis of evidence, not tradition. Critical skills are therefore crucial to modern scientific medicine. Importantly, medicine is a moral enterprise as well as a scientific one. Many clinical decisions involve a combination of factual and ethical aspects. It is as important to be able to give good reasons for the ethical aspects of clinical decisions as it is for the science. Society increasingly expects this from doctors as part of transparent decision-making.
Clinical decision-making
Authors: Peto Timothy E.A. , Peto Philippa 
Published: February 2020

Abstract
Clinicians make decisions at every stage of the patient pathway. In routine practice complex decisions are often made rapidly using ‘intuition’ or common sense, but this can lead to suboptimal management plans. Clinical decision analysis is a way of formalizing the logical process behind decision-making, and when combined with evidence from medical research is described as the practice of evidence-based medicine. In practice, most clinicians do not have the time, intellectual energy, or training to perform a formal clinical decision analysis and they tend to use short cuts and go for the ‘safe’ decision which is suitable for the ‘average patient’ and often in keeping with guidelines for local practice. However, clinicians who follow the logical process of clinical decision analysis find it easier to live with the uncertainty of an inexact science and subjective wishes of the patient.
Science in medicine: When, how, and what
Authors: Bynum William F. 
Published: February 2020

Abstract
Science has always been part of Western medicine, although what counts as scientific has changed over the centuries, as have the content of medical knowledge, the tools of medical investigation, and the details of medical treatments. This brief overview develops a historical typology of medicine since antiquity. It divides the ‘kinds’ of medicine into five sections: bedside medicine, developed by the Hippocratic doctors in classical times; library medicine, associated with the scholastic mentality of the Middle Ages; hospital medicine, central to French medicine of the early 19th century; social medicine, which is about prevention, both communal and individual; and laboratory medicine, which has its natural home in the research establishment and is a critical site for the creation of medical knowledge, setting the standards for both medical science and scientific medicine.
Large-scale randomized evidence: Trials and meta-analyses of trials
Authors: Baigent Colin , Peto Richard , Gray Richard , Staplin Natalie , Parish Sarah , Collins Rory 
Published: February 2020

Abstract
Clinical trials generally need to be able to detect or to refute realistically moderate (but still worthwhile) differences between treatments in long-term disease outcome. Large-scale randomized evidence should be able to detect such effects, but medium-sized trials or medium-sized meta-analyses can, and often do, yield false-negative or exaggeratedly positive results. Hundreds of thousands of premature deaths each year could be avoided by seeking appropriately large-scale randomized evidence about various widely practicable treatments for the common causes of death, and by disseminating this evidence appropriately. This chapter takes a look at the use of large-scale randomized evidence—produced from trials and meta-analysis of trials—and how this data should be handled in order to produce accurate result.
Financing healthcare in low-income developing countries: A challenge for equity in health
Authors: Sambo Luis G. , Simões Jorge , do Rosario O. Martins Maria 
Published: February 2020

Abstract
Low-income developing countries remain challenged by the increasing demand for essential healthcare combined with governments’ inability to mobilize and allocate adequate financing to health systems. According to their country specific contexts, they need to improve the equity and efficiency of their health systems, in particular their public sector management, and increase their governmental health spending through enhanced domestic resource mobilization and more efficiency in public spending. They need to sustain external assistance and implement social protection policies that decrease out-of-pocket payments, thereby preventing people with catastrophic illness from becoming impoverished. Economic growth and increased health spending alone are not enough to scale-up healthcare coverage and achieve better health outcomes. These must be combined with accountability of results, transparent management of public funds, and multisectoral efforts with community involvement at implementation level.
Intracellular signalling
Authors: Floto R. Andres 
Published: February 2020

Abstract
This chapter outlines the general principles of intracellular signalling. Focusing on cell surface receptors, the requirements for effective transmission of information across the plasma membrane are outlined. The principal mechanisms utilized in mammalian signal transduction are described. For each, the pathological consequences of aberrant signalling and means by which pathways can be pharmacologically targeted are described in molecular terms.
Intracellular signalling pathways permit the transmission and integration of information within cells. Mammalian receptor signalling relies on only a small number of distinct molecular processes which interact to determine cellular responses. Rapid advances in our knowledge of the mechanisms of intracellular signalling has greatly increased understanding of how cells function physiologically, how they malfunction pathologically, and how their behaviour might be manipulated therapeutically.
The evolution of therapeutic antibodies
Authors: Waldmann Herman , Winter Greg 
Published: February 2020

Abstract
The development of rodent monoclonal antibodies opened the door to the creation of antibodies specific to soluble and cell-surface antigens. ‘Humanized’ therapeutic antibodies have emerged as major blockbuster drugs for the treatment of cancer, immune, and inflammatory disorders—the so-called biologics. Much of this revolution was spearheaded in Cambridge, England, initiated by the research of Cesar Milstein and George Köhler at the MRC Laboratory of Molecular Biology and who, with N.K. Jerne, shared the 1984 Nobel Prize for Medicine or Physiology. As related in this personal perspective, Cambridge scientists and clinicians took up the challenge to develop the original murine antibodies into powerful pharmaceuticals that can be administered repeatedly without the dire consequences of alloimmunization. In this short chapter, two scientists who made seminal contributions to this field and remain actively engaged in its development give a personal account of how these remarkable developments came about.
Adaptive immunity
Authors: Klenerman Paul 
Published: February 2020

Abstract
The adaptive immune response is distinguished from the innate immune response by two main features: its capacity to respond flexibly to new, previously unencountered antigens (antigenic specificity), and its enhanced capacity to respond to previously encountered antigens (immunological memory). These two features have provided the focus for much research attention, from the time of Jenner, through Pasteur onwards. Historically, innate and adaptive immune responses have often been treated as separate, with the latter being considered more ‘advanced’ because of its flexibility. It is now clear this not the case, and in recent years the molecular basis for these phenomena has become much better understood.
Immunodeficiency
Authors: Hambleton Sophie , Marshall Sara , Kumararatne Dinakantha S. 
Published: February 2020

Abstract
Immunodeficiency is caused by failure of a component of the immune system and results in increased susceptibility to infections. The possibility of an underlying immunodeficiency should be considered if a patient has: serious, persistent, unusual, or recurrent infections; failure to thrive in infancy; known family history of immunodeficiency; unexplained lymphopenia in infancy; or a combination of clinical features characteristic of a particular immunodeficiency syndrome. The nature of the microbial infection in a particular patient provides a clue to the likely cause of immunodeficiency. Primary immunodeficiency diseases are heritable disorders that result in defects in an intrinsic component of the immune system. Secondary immunodeficiencies are caused by conditions that impair the normal function of the immune system and include viral infections, myelomatosis, non-Hodgkin’s lymphoma, severe renal or liver failure, and use of therapeutic agents which impair immunity.
The genetics of inherited cancers
Authors: Eeles Rosalind A. 
Published: February 2020

Abstract
All cancer can be termed ‘genetic’ as the disease is caused by somatic cell mutations (alterations in the DNA code), which result in abnormal cellular growth and/or proliferation. Most of these mutations are sporadic (only occurring in the cancer cell), but some are due to the inheritance of a germline mutation in a cancer predisposition gene. Cancer predisposition genes can be rare and confer a high cancer risk (about 10-fold lifetime relative risk), or common and confer a low to moderately increased risk (from just over onefold, up to two- to threefold). They have been shown to be involved in causing some of most common cancers as well as some rare cancers. Cancer genetics will become part of mainstream clinical pathways for cancer care in the coming years and is likely to contribute to healthcare that is tailored to individual patients.
Care of the dying person
Authors: Kite Suzanne , Hurlow Adam 
Published: February 2020

Abstract
The care a patient receives in the last hours to days of life is important: it has a significant impact on their quality of life and death, and on the psychological well-being of their loved ones and the team delivering care. Most deaths are not sudden or unexpected, but recognition that a patient is dying is challenging. Clinicians’ estimates of survival are often inaccurate, with a tendency towards over-optimism, yet clinical teams must be able to agree goals and care plans with patients and their loved ones while acknowledging and communicating the uncertainty inherent to prognostication. Shared individualized decision-making is essential: patients must be offered the opportunity to participate in decisions, but a preference not to be involved should be respected. The aim must be to agree an individual plan of care that incorporates the needs and preferences of the person and those close to them.
Clinical approach
Authors: Ellis Christopher J. 
Published: February 2020

Abstract
The clinical approach to patients with likely infection begins with a focused history, leading on to a clinical examination which assesses the extent of the physiological derangement and looks for a focus of infection. Standard physiological measures define likely sepsis (see Chapter 8.1.2), which is the commonest reason for their sudden derangement in hospitalized patients. Investigations should be phased and must not delay the start of potentially life-saving treatment, the response to which must be carefully followed, especially when treatment has to be started before a complete or certain diagnosis is possible, and compared with the likely speed of response for the putative condition being treated. There is increasing evidence that delays in initiating appropriate therapy, especially antimicrobial medication and circulatory support, increase mortality.
Rhabdoviruses: Rabies and rabies-related lyssaviruses
Authors: Warrell Mary J. , Warrell David A. 
Published: February 2020

Abstract
The Rhabdoviridae are a large family of RNA viruses, two genera of which infect animals: the genus Lyssavirus contains rabies and rabies-related viruses that cause at least 55,000 deaths annually in Asia and Africa. The risks and problems posed by rabies and other lyssaviruses vary across the world. Viruses can penetrate broken skin and intact mucosae. Humans are usually infected when virus-laden saliva is inoculated through the skin by the bite of a rabid animal, usually a dog. Although the greatest threat to man is the persistent cycle of infection in stray dogs, several other terrestrial mammal species are reservoirs of infection. In the Americas, bat viruses and also classic type 1 rabies and insectivorous bats have become the principal vectors of infection to humans in the United States of America. Elsewhere in the world, there is increasing evidence of widespread rabies-related lyssavirus infection of bats.
HIV/AIDS
Authors: Fidler Sarah , Peto Timothy E.A. , Goulder Philip , Conlon Christopher P. 
Published: February 2020

Abstract
Since its discovery in 1983, the human immunodeficiency virus (HIV) has been associated with a global pandemic that has affected more than 78 million people and caused more than 39 million deaths. Globally, 36.9 million (34.3–41.4 million) people were living with HIV at the end of 2013. An estimated 0.8% of adults aged 15–49 years worldwide are living with HIV, although the burden of the epidemic continues to vary considerably between countries and regions. Sub-Saharan Africa remains most severely affected, with nearly 1 in every 20 adults living with HIV and accounting for nearly 71% of the people living with HIV worldwide. The impact of HIV in some African countries has been sufficient to reverse population growth and reduce life expectancy into the mid-30s, although HIV incidence has declined in some of these high-prevalence countries. However, there are large-scale HIV epidemics elsewhere (e.g. India, the Russian Federation, and Eastern Europe).
HIV in low- and middle-income countries
Authors: Grant Alison D. , De Cock Kevin M. 
Published: February 2020

Abstract
The HIV pandemic has disproportionately affected people in low- and middle-income countries. In many countries in sub-Saharan Africa, HIV infection is established in the general population: in southern Africa, which is particularly severely affected, adult HIV prevalence has reached 30% in some areas. Local epidemiology depends on the balance between incidence (due to sexual contact, mother-to-child transmission, or exposure to blood or blood products) and mortality, and the effect of antiretroviral therapy on both mortality and transmission. The main route of transmission is sex between men and women. The manifestations of HIV disease vary by geographical region, reflecting increased frequency of exposure in low- and middle-income countries to common pathogens such as tuberculosis, non-typhoid salmonellae, and Streptococcus pneumoniae. People with advanced immunosuppression are also at risk of disease due to geographically restricted opportunistic pathogens (e.g. leishmania and Tarolomyces marneffei).
Meningococcal infections
Authors: Brandtzaeg Petter 
Published: February 2020

Abstract
Neisseria meningitidis is an obligate human Gram-negative diplococcus. It is carried in the nasopharynx by about 3–10% of people, with most strains being harmless and inducing immunity. Pathogenic strains usually belong to specific clones that are encapsulated, express pili, and the major porin, PorA. Serogroups A, B, and C usually account for more than 90% of all invasive isolates. Meningitis is the commonest presentation; preceded by low-grade meningococcaemia. After transition to the subarachnoid space the meningococci proliferate to high levels in the cerebrospinal fluid. Clinically the patients develop fever, subsequently a petechial rash and increasing symptoms of meningitis. If adequately treated with antibiotics, case fatality is less than 1–2% in industrialized countries, but higher in developing countries. Brain oedema leading to herniation of the cerebellum is the main cause of death. Neurosensory hearing loss is the major complication.
Cholera
Authors: Lima Aldo A.M. , Guerrant Richard L. 
Published: February 2020

Abstract
Cholera, the dreaded scourge causing death from dehydrating diarrhoea, existed for centuries in South Asia until, in 1817, it broke out along trade routes; since then there have been seven pandemics across all six inhabited continents. Vibrio cholerae is a Gram-negative organism that can be subdivided into over 200 serogroups based on the somatic O antigen, with only serogroups O1 and O139 causing epidemic and pandemic disease. Historically it has killed millions from dehydrating diarrhoea, encouraged the birth of modern epidemiology, the sanitary revolution, and oral rehydration therapy; it persists today as a glaring reminder of poverty and inadequate water/sanitation. Contaminated food (especially undercooked seafood) is the usual route of transmission in developed countries; contaminated water and street food vendors are more common vehicles in less developed countries.
Haemophilus ducreyi and chancroid
Authors: O’Farrell Nigel 
Published: February 2020

Abstract
Haemophilus ducreyi is a Gram-negative, facultative anaerobic bacillus that is the cause of chancroid. The condition was endemic in sub-Saharan Africa and the Caribbean, but the overall global incidence of the condition has decreased dramatically since the mid-1990s. After an incubation period of 4–10 days, presentation is with a tender genital papule that develops into a pustule and then an ulcer with a ragged undermined edge and a yellow base that bleeds readily. The usual sites of infection in men are the prepuce and coronal sulcus, and in women the labia minora and fourchette. Inguinal lymphadenopathy is found in about half the male cases. Chancroid is an important risk factor for the transmission of HIV infection. HIV infection may result in atypical manifestations of chancroid.
Nucleic acid amplification tests are the optimal method of diagnosing H. ducreyi. Treatment is with either ciprofloxacin, erythromycin, azithromycin, or ceftriaxone.
Plague: Yersinia pestis
Authors: Prentice Michael 
Published: February 2020

Abstract
Bubonic plague is a flea-borne zoonosis caused by the Gram-negative bacterium Yersinia pestis, which mainly affects small burrowing mammals including domestic rats. Human disease occurs in endemic countries—currently mainly in Africa (including Madagascar)—following bites from fleas recently hosted by a bacteraemic animal. Historical use of Y. pestis as a biological warfare agent has raised fears of its future use in bioterrorism. The commonest presentation is acute painful lymphadenitis (80–95% of suspected cases), with sudden onset of fever, chills, weakness, headache, and development of an intensely painful swollen lymph node (bubo). Primary septicaemia with no bubo occurs in 10% of cases. Spread to the lungs occurs in less than 10% of cases, resulting in pneumonia which can result in onward respiratory transmission by droplet infection. Overall mortality without treatment is 50–90%.
Pasteurella
Authors: Morgan Marina S. 
Published: February 2020

Abstract
Pasteurella multocida is an important human Gram-negative pathogen residing primarily in the oropharynx of mammals and transmitted through bites and scratches. Presentation is typically within 12 h of injury with rapidly spreading cellulitis or sepsis, leading to serious morbidity and mortality (up to 40%) if untreated. Diagnosis is clinical: fresh bite wound cultures are unhelpful, but the organism is usually cultured in cases with established infection, especially if presenting within 24 hours of the injury. Treatment requires thorough wound debridement, with delayed closure if possible, along with antimicrobials to provide empirical cover against pasteurellae and all the other expected pathogens (e.g. amoxicillin-clavulanate plus ciprofloxacin, or meropenem plus clindamycin). Prevention is by avoidance of animal bites or scratches and prompt hygienic management of wounds: antibiotic prophylaxis (amoxicillin-clavulanate or—for the penicillin allergic—doxycycline or azithromycin) should be reserved for high-risk bites (e.g. cat bites) or high-risk wounds that are difficult to debride.
Anthrax
Authors: Brown Arthur E. 
Published: February 2020

Abstract
Anthrax is primarily a disease of herbivorous mammals, caused by the Gram-positive rod Bacillus anthracis, which causes human infection when its spores enter the body, most commonly from handling infected animals or animal products. The disease occurs in most countries of the world, but is only sporadic where the condition is controlled in livestock by vaccination programmes. Anthrax is a leading agent of biological warfare. After entry into the body, anthrax spores are phagocytosed by macrophages and carried to regional lymph nodes, where they germinate to produce vegetative bacilli that enter the bloodstream. These produce anthrax toxins, which have effects including impairment of cellular water homeostasis and of many intracellular signalling pathways.
Leprosy (Hansen’s disease)
Authors: Lockwood Diana N.J. 
Published: February 2020

Abstract
Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae, an acid-fast intracellular organism not yet cultivated in vitro. It is an important public health problem worldwide, with an estimated 4 million people disabled by the disease. Transmission of M. leprae is only partially understood, but untreated lepromatous patients discharge abundant organisms from their nasal mucosa into the environment. It was first identified in the nodules of patients with lepromatous leprosy by Hansen in 1873. M. leprae preferentially parasitizes skin macrophages and peripheral nerve Schwann cells. A second agent of leprosy M. lepromatosis which diverged form M. leprae 10 million years ago has also been recognized as causing leprosy in 40 + patients and the main focus of origin is Mexico. The importance of this organism will be determined over the next few years.