bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Now the Time … ?
Authors: de Bie Robertus M. A.
Published: November 2017

Deep-brain stimulation is now well established as the therapy of choice for Parkinson’s disease with motor complications, although the decision to undergo surgery has always relied on a patient experiencing a sufficient amount of disability to outweigh the associated risks of surgery and also on a physician who believes surgery is appropriate. In recent years, a number of studies have provided evidence for having this discussion earlier in the course of the disease to maximize the potential of surgery. This chapter discusses the most important considerations when determining whether deep-brain stimulation is appropriate for a patient with Parkinson’s disease.
Parkinson’s Disease with an Unusual Tremor
Authors: Walsh Richard A.
Published: November 2017

Multiple system atrophy represents a form of atypical parkinsonism that is challenging to manage and results in rapidly progressive disability and dependence in the absence of effective disease-modifying or symptomatic therapies. Two syndromes are recognized, both associated with autonomic dysfunction—MSA-C and MSA-P, with a predominance of parkinsonian and cerebellar features, respectively. Magnetic resonance imaging can assist with an early diagnosis, demonstrating certain features that can be considered diagnostic in the right clinical context. The typical changes described may not be apparent on an initial scan, so it is worth repeating imaging 1 or 2 years later if the clinical features and course are typical of multiple system atrophy.
Twists and Turns
Authors: Fox Susan H.
Published: November 2017

Focal dystonia is the most common clinical manifestation of primary dystonia. The focal and sometimes task-specific nature of the symptoms makes daily drug therapy less attractive due to a requirement for exposure to high doses of anticholinergic agents that are typically only minimally effective. Botulinum toxin therapy can be targeted to a specific muscle group that is judged to be most active, providing relief for 3 months although not necessarily modifying the underlying disease pathophysiology, which remains uncertain. Deep-brain stimulation is currently reserved for the most resistant cases in which the disability or pain derived from the dystonia justifies consideration of neurosurgery.
Slow with an Altered Sensorium
Authors: Walsh Richard A.
Published: November 2017

Catatonia is a neuropsychiatric syndrome that represents an uncommon clinical end point of a number of primary psychiatric and neuromedical conditions. The common pathophysiology may be associated with reduced dopaminergic activity within the frontal–subcortical circuitry. The incidence of catatonia was considerably higher before the introduction of neuroleptics, which reduced its association with poorly controlled schizophrenia. Catatonia is a syndrome with a spectrum from benign to malignant, the latter being a medical emergency with a significant mortality rate. Treatment is with benzodiazepines, which can be sufficient in less severe cases, and in more resistant or malignant cases with life-threatening clinical features, electroconvulsive therapy is sometimes applied.
Wakeful Unresponsiveness
Authors: Fox Susan H.
Published: November 2017

NMDA receptor encephalitis is a member of the growing group of antibody-mediated neurological syndromes that can present acutely to neurological services. In the past, these entities were undoubtedly misdiagnoses as viral encephalitis or schizophrenia. The identification of the NMDA receptor antibody and a stereotypical phenotype has greatly improved the chance of a diagnosis in these patients. Furthermore, there is good evidence for the use of early immunotherapy, which may need to be sustained and increased in resistant cases that may still achieve a full recovery. The presence of an ovarian teratoma must be excluded in young females, although young males and females may also be affected in the absence of an underlying tumor.
Behind the Glories of War
Authors: Aminoff Michael J.
Published: November 2017

The Peninsular War (1807–1814), contemporary military medical services, the famous British retreat to Corunna and evacuation from Spain to England, and the care and treatment of the wounded are discussed. Bell volunteered his services at the Haslar Hospital, where many of the evacuated were treated. He made sketches and oil paintings of the wounded and published a dissertation on the treatment of gunshot wounds. He later volunteered to treat the wounded of the Battle of Waterloo (1815), and again he sketched the injured. The famous Corunna oil paintings, now at the museum of the Royal College of Surgeons in Edinburgh, and the Waterloo paintings, at the Army Medical Services Museum in Aldershot, England, are a dramatic contrast to the usual images and portraits of the glories of war.
The Organization of the Nervous System
Authors: Aminoff Michael J.
Published: November 2017

Bell came up with a number of original concepts concerning the organization and operation of the nervous system in health and disease. The focus of Bell’s 1811 book was the brain, not the nerve roots. Bell suggested that parts of the brain differ in function; peripheral nerves are composed of nerve fibers with different functions; nerves conduct only in one direction; sense organs are specialized to receive only one form of sensory stimulus; and perception depends on the part of the brain activated. In later publications, he described a sixth (muscle or proprioceptive) sense and the circle of the nerves subserving it; movement and reciprocal innervation; and the long thoracic nerve (Bell’s nerve).
Clinical Observations on the Nervous System
Authors: Aminoff Michael J.
Published: November 2017

With his remarkable knowledge of anatomy and his analytical mind, Bell developed into an outstanding clinical neurologist even before the specialty had been invented. Thus it was that in his later years, when finally he returned to the University of Edinburgh as professor of surgery, referrals and requests for consultation were often for him to provide a neurological opinion rather than to perform surgical operations. His clinical observations regarding motor or sensory disturbances involving the face are of particular interest given his interests in the facial expression of emotions and the innervation of the face. Bell described or elaborated on several clinical disorders, although not always recognizing them as distinct entities—Bell’s palsy and spasms; the numb chin; motor neuron diseases; muscular dystrophy; myotonia; various movement disorders (torticollis and writer’s cramp); atlantoaxial dislocation; trigeminal neuralgia; and referred pain.
For God and Country
Authors: Aminoff Michael J.
Published: November 2017

Charles Bell and his wife both had ecclesiastical backgrounds. Like many contemporary scientists, Bell was a creationist who believed in intelligent design. He not only published notes and supplementary dissertations to William Paley’s Natural Theology but also wrote a treatise on Animal Mechanics and a Bridgewater Treatise on The Hand. Natural theology had begun to decline in importance in the 1830s, however, seeming increasingly tired and dated in an era of change. Bell’s anatomical teaching—framed on the concept of intelligent design—was thus overshadowed by the concepts of Buffon, Geoffroy, Lamarck, Robert Grant, and Charles Darwin and by the teachings of younger, more modern professors. Nevertheless, national honors came his way—the Gold (Royal) Medal of the Royal Society for his work on the nervous system and a knighthood in 1831.
Respiratory complications and management of severe CF lung disease
Authors: Innes J Alastair
Published: November 2017

This chapter covers the most common medical complications of severe CF lung disease, excluding the treatment of infection exacerbation. The section on haemoptysis covers severity assessment, medical and interventional radiological approaches to managing this problem. The particular risks of pneumothorax in CF are then discussed, including the factors guiding referral to surgery. The management of acute and chronic respiratory failure in CF is covered. This includes the indications for home oxygen and for non-invasive ventilation, and guidance on how these should be used in CF. Finally, there is a section on terminal care in cystic fibrosis, covering the management of the transition to palliative management at the end of life, and appropriate strategies to support patient and family in advanced disease.
Lung transplantation
Authors: Blaikley John , Fisher Andrew J
Published: November 2017

This chapter describes common issues along the transplantation journey from assessment to common conditions that are diagnosed post transplantation. Assessment for transplant suitability against several objective criteria is covered as well as the importance of optimizing techniques prior to this. Recent advances mean that some patients can now be bridged to transplant using extracorporeal membrane oxygenation (ECMO) when previously they would have been removed from the transplant list. Drawbacks to ECMO are discussed. Ex-vivo lung perfusion (EVLP) of a donor organ is covered.
Follow-up is considered, especially in the early phase whilst being stabilized on their new medications as well as monitoring for the development of lung rejection (acute and chronic). These conditions often present when patients are being seen away from the transplant centre. CF patients have the best outcomes of the groups after lung transplantation, emphasising that lung transplantation should be considered in this specific group of patients.
Fertility, contraception, and pregnancy
Authors: Edenborough Frank P
Published: November 2017

This chapter describes the physiological effect of CFTR dysfunction on the development of the reproductive system. Young people with CF and their parents are poorly educated regarding sexual function and becoming parents themselves. They often wish to learn this from their CF teams. Male and female potency, reproductive genetics, and the need for genetic and general counselling before embarking on pregnancy are covered. Contraception, emphasizing the need to avoid unwanted pregnancy and sexually transmitted diseases, and assisted reproductive techniques are described. We discuss the evolving medical and obstetric management of pregnancy, including the likely need for optimizing drug treatment or escalating to more intensive treatment for intercurrent infection. Optimal delivery in the context of maternal health, fetal risks, and longer term maternal outcomes are discussed. Pregnancy post transplantation and termination of unwanted pregnancy or where the mother is too poorly to continue conclude the chapter.
Introduction to Part 3: All the resources of the community
Authors: Omaswa Francis , Crisp Nigel
Published: November 2017

Chapter 7 describes how many African health leaders have been very effective in using the resources of their community in their efforts to improve health. They have improvised and innovated: pressing sometimes very unlikely equipment, facilities, and people into service. It covers accounts from Kenya and Nigeria about how two leaders have developed new approaches to tackling disease through building on the strengths of local communities. It also describes the wider political, economic, and social context and the work of the AU, which is covered in detail in a later chapter.
Twenty years of improving access to healthcare in Rwanda
Authors: Binagwaho Agnes
Published: November 2017

Chapter 17 describes the establishment and development of a patient-centred healthcare delivery platform in Rwanda, breaking geographic barriers by ensuring equitable distribution of health facilities aligned to the administrative structure of the country, and also by mitigating financial barriers with a community based insurance system that has provided coverage for more than 90% of the population by 2011. It emphasizes the importance of a holistic approach to providing care that is community based, driven by Rwandan leaders with international support, and being part of the wider development of the country.
HIV/AIDS and National Health Insurance in South Africa
Authors: Crisp Nigel
Published: November 2017

Chapter 18 describes how Dr Motsoaledi, the South African Health Minister, set about leading the fight on HIV/AIDS in South Africa, and introducing a national health insurance scheme in order to offer healthcare to every person in the country, by building on the work that was already underway. It describes his complex story, with many confusing cross-currents and elements of conflict and intrigue, and how a large part of the Minister’s role involved trying to cut through the confusion, offer a clear pathway for the future, and communicate
Coverage of the poor—innovative health financing in Ghana
Authors: Nyonator Frank
Published: November 2017

Chapter 19 describes the journey that Ghana has been on since 2003 as it sought to bring together existing community based health insurance schemes of many sorts within a single national framework, which offered a package of care to all its citizens—however poor and from whatever background. It covers the challenges in integrating the existing schemes, in applying different aspects of the policy, in funding, and in reaching the poorest. It also discusses how the government has changed and with it some aspects of policy, and how, after 10 years, around a third of the population are active members of the National Health Insurance Scheme and there is a foundation in place for continuing the journey to ensure that health services are available to everyone as the country continues to grow and prosper.
Introduction to Part 6: The future
Authors: Omaswa Francis , Crisp Nigel
Published: November 2017

Chapter 21 turns to the future. It describes the different challenges that three generations of leaders have had to face in Africa—from colonial times, via the HIV/AIDS epidemic, and on to a time when Africa takes its place fully on the world stage. Lessons are being learned from each stage for the future.
Science before science
Authors: McCann Shaun R.
Published: November 2017

Blood occupies a central part of the human psyche. It has long been regarded as essential for life, and as a source of the life force itself. Every civilization possesses records which chart the human fascination with blood and bloodletting in terms of both ritual and medicine. As a basis for the understanding of the field of haematology, it is important to ground the study in the cultural history of the substance giving rise to the topic. In this chapter, the attitudes of the ancient Greeks (including Herodotus and Pythagoras), Islamic scholars (such as Ibn al-Nafis), Chinese medicine, and Indian medicine towards blood is discussed, as are the modern vampire legends.
The Enlightenment and the unravelling of the circulation
Authors: McCann Shaun R.
Published: November 2017

The Enlightenment brought about widespread cultural changes. In the fields of science and medicine, these changes were represented by technological and technique-driven advances which revolutionized the understanding of long-queried phenomena. The Enlightenment also brought about the first experiments with blood transfusion. In the seventeenth century, attempts to transfer blood between animals and humans were shown to be successful; however, the political reaction to the practice in some countries, such as France, was to ban the act. Only later, in the nineteenth century, did new developments in the practice, along with advances forged in the field of the Spanish Civil War and Word War II, and the development of new technologies—in the form of the plastic bag—did what can be recognized as modern blood transfusion come to be.
Radiation and transplantation
Authors: McCann Shaun R.
Published: November 2017

There is a paradoxical relationship between ionizing radiation and leukaemia. On the one hand, it is known that exposure to high doses of ionizing radiation causes leukaemia; on the other hand, the preparative regimens for stem cell transplantation, which can cure leukaemia, often contain total body irradiation. This chapter discusses the effect war has had on medical technology, with specific regard to the use of stem cells for the treatment of blood disorders such as leukaemia and sickle cell anaemia. The transfer of laboratory techniques to the clinical practice of stem cell transfer and bone marrow transplantation is also discussed.
Leukaemia
Authors: McCann Shaun R.
Published: November 2017

The word leukaemia still is associated with foreboding and a fear of premature death. Steady advances have been made in the treatment of childhood leukaemia but, with notable exceptions, the same is not true in adults. The so-called genetic/molecular revolution has extended the understanding of the pathogenesis of many forms of leukaemia but, as yet, has rarely facilitated cure. With the introduction of tyrosine kinase inhibitor therapy, chronic myeloid leukaemia is the obvious exception but it still needs to be seen as to whether the cytogenetic/molecular revolution can provide cures for many elderly patients with leukaemia, as such patients respond poorly to chemotherapy. Haematopoietic stem cell transplantation, although toxic, expensive, and difficult, still provides a cure for many patients. In spite of all these advances, however, most adults with acute leukaemia or myelodysplastic syndrome are destined to die from their disease, and the causes of these fatal illnesses continue to elude researchers.
‘If you prick us, do we not bleed?’
Authors: McCann Shaun R.
Published: November 2017

William Shakespeare and many others recognized the connection between trauma and bleeding, and the association of bleeding with childbirth is well established. However, even though the associations are well known, the understanding of the mechanisms underlying blood clotting is relatively recent. Bleeding and clotting continue to be major causes of mortality and morbidity. Cerebrovascular accidents and myocardial infarction, together with cancer, continue to be the main causes of death worldwide. In spite of advances in the understanding of the mechanisms of haemostasis and thrombosis in health and disease, there is still much to learn and a lot more to do to reduce the incidence of bleeding and clotting.
Molecules, genes, and gene therapy
Authors: McCann Shaun R.
Published: November 2017

The twenty-first century has brought many innovations in haematology, with improved diagnostic technology, which may inform treatment choices for malignant diseases, and a better understanding of the genetics and/or epigenetics underlying many diseases. Unfortunately, the aetiology of most of these diseases still eludes us, and some common diseases such as sickle cell disease await simple, inexpensive, and widely available curative treatment. For reasons that are often obscure, some diseases have become fashionable and attract large research financial backing, whereas some do not. With the advent of advanced technology and an improved understanding of disease mechanisms, most haematological malignancies should enjoy the same success as the treatment of childhood acute lymphoblastic leukaemia and chronic myeloid leukaemia.
The importance of nutrition and lifestyle to healthy development
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Good fetal and infant nutrition, whether derived from the mother via the placenta during gestation or via breast milk after birth, consists of the macronutrients protein, carbohydrates, and fats, all of which are needed for building the fundamental components of the body, and micronutrients such as vitamins and trace elements, which are essential structural components and cofactors in metabolic processes. Understanding the concept of a ‘balanced diet’ and the implications of maternal body composition is critical for pregnant and breastfeeding women to ensure that their metabolic adaptation to pregnancy and lactation is appropriate and that their offspring gets the required nutrients in the appropriate amount and proportion to ensure optimal development. An unbalanced diet, or over- or under-nutrition, can increase the risks of low birthweight and gestational diabetes and result in unfavourable metabolic adjustments by the fetus.
Practicalities: understanding nutrient recommendations
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

There has been much research in recent years on the nutritional requirements of mothers during pregnancy, as well as an increasing focus on the nutrition of women before conception. Because there has been much confusion with regards to some nutrients such as vitamin D, iron, and polyunsaturated fatty acids, the second section of this book contains specific advice, based on an in-depth interpretation of the current clinical and scientific literature, on macro- and micronutrient dietary components and their effects on pregnancy and lactation outcomes. This chapter provides an introduction for the subsequent chapters in this section by discussing the practicalities of understanding nutrient recommendations. The chapter also gives an overview of the terms used by various agencies to describe nutrient requirements. In addition, the chapter goes into detail about food labelling standards from the US, Canada, the UK, Australia, and New Zealand.
Vitamin B1 (thiamine) in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Vitamin B1 (thiamine) is involved in nervous system and muscle function and is essential for carbohydrate metabolism. Deficiency is common in Asia, where diets are often high in thiamine-depleted polished rice and can be low in other food sources. Pregnancy imposes an increasing requirement for thiamine over the course of gestation, and deficiency can lead to widespread metabolic disturbances affecting the placenta and fetus. Nutritional deficiency for thiamine is rare in people who consume a moderately varied diet that contains whole grains. However, excessive vomiting in pregnancy can cause thiamine depletion, in which case antenatal vitamins containing thiamine and other B vitamins may be beneficial.
Vitamin D in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Vitamin D, which is synthesized in skin exposed to UV light, or is consumed in the diet, plays a key role in maintaining bone integrity via the regulation of calcium and phosphorus homeostasis. It also influences a number of extra-skeletal processes, including immune function and blood glucose homeostasis. Maternal vitamin D deficiency in pregnancy leads to poor fetal skeletal mineralization in utero that can manifest as rickets in newborns. In addition to skeletal effects, women with very low vitamin D status face increased risks of other adverse pregnancy outcomes and possible long-term effects on their own health and that of their offspring. However, controversy remains over definitions of vitamin D sufficiency and deficiency, complicating recommendations on maternal intakes. At a minimum, all pregnant women should take a supplement of 400 IU/day, in addition to sensible sun exposure and increasing their intake of food sources.
Vitamins C and E and other antioxidants in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Pregnancy is characterized by oxidative stress, wherein high metabolic demands are accompanied by heightened oxygen requirements in tissues. Additionally, a number of disorders of pregnancy are characterized by a reduction in antioxidant activity. Consequently, it has been hypothesized that maternal supplementation with antioxidants, particularly vitamins C and E, may be beneficial in preventing the occurrence of these disorders. Other important dietary antioxidants include carotenoids, and polyphenols (flavonoids). In general, studies of the effect of providing supplementary vitamin C and E to improve pregnancy outcomes have been inconsistent or have shown no positive effect; some evidence suggests high-dose vitamin E may be harmful. These and other antioxidants are necessary in pregnancy but should ideally be obtained from food sources.
Iron in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Iron requirements increase approximately 2.5-fold by the end of pregnancy, representing the largest relative increase in nutrient requirements for pregnant women. The total additional iron requirement in the third trimester is 9#amp;#x2013;12 mg/day above pre-pregnancy needs, and even with this additional intake, women need to enter pregnancy with iron stores of approximately 500 mg to be able to fully meet the demands of pregnancy. The prevalence of iron deficiency and anaemia is therefore very high among pregnant women and can result in cognitive and motor deficits in the infant that may be irreversible. Prevention of deficiency is therefore critical. Building sufficient iron stores prior to conception is preferable, as it is difficult to obtain adequate iron from diet alone to meet late pregnancy requirements. Iron supplementation of 30 mg/day should be considered, particularly if dietary intake of meat is low.
Selenium in pregnancy and breastfeeding
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

The essential trace mineral selenium is a component of antioxidant enzymes and proteins that regulate thyroid hormone metabolism and immune function. Thyroid metabolism is sensitive to selenium in the diet, and selenium deficiency can exacerbate the effects of iodine deficiency. Selenium deficiency is also associated with enhanced viral virulence and is a risk factor for perinatal transmission of HIV. Several selenium-dependent proteins are important in male fertility. Most pregnant women in developed countries will be able to meet selenium requirements through their usual diet, but because some foods differ widely in selenium content according to their geographical sources, a variety of foods should be eaten to ensure adequate intake and to avoid toxicity. Taking selenium supplements in addition to adequate dietary intake is not recommended, as the safe intake range is narrow.
Guidelines for the pre-conception period
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Where possible, pre-conception counselling is desirable for both prospective parents in order to address issues of lifestyle and nutrition so that pregnancy can proceed with the best possible start. If dieting is necessary this should be initiated as far in advance of the pregnancy as possible, because inadequate nutrition around the time of conception can influence the fetal growth trajectory and weight at birth. Regardless of BMI, women should also be encouraged to engage in regular aerobic exercise. Nutritional requirements in the pre-conception period include adequate amounts of oily fish to provide omega-3 fatty acids. All women planning a pregnancy should receive 400 #amp;#x00B5;g of folic acid daily, and vitamin B12 and vitamin D supplementation may be necessary, particular for vegetarians. Other vitamins and minerals should be considered, particularly iron and iodine, but most should be obtainable from a balanced diet. Harmful behaviours and environmental exposures should be avoided.
Guidelines for breastfeeding and weaning
Authors: Gluckman Sir Peter , Hanson Mark , Seng Chong Yap , Bardsley Anne
Published: November 2017

Breastfeeding provides almost all of the nutrient requirements for the growing infant to the age of 6 months. Complementary foods rich in iron should be introduced by 6 months, but continued breastfeeding past this point is still beneficial to the infant. It is also beneficial for the mother, reducing postpartum weight retention and lowering the risk of breast and other gynaecological cancers. Breastfeeding women have increased energy requirements to meet the energy costs of milk production. Some specific nutrient requirements also increase during lactation. Excess alcohol consumption, smoking, illicit drugs, and acute exposures to known toxic substances should be avoided. Some prescription and over-the-counter drugs are suitable for use during lactation, including some pain medications, anti-infectives, anti-hypertensives, and drugs to treat postpartum depression. These should be taken under the advice of a physician.
The Pharmaceutical Phoenix Rises
Authors: Schmidt Dieter , Shorvon Simon
Published: November 2017

This chapter considers the evolution of drug therapy between 1860 and 1970, a period dominated by five compounds: bromide, phenobarbital, phenytoin, carbamazepine, and valproate. These drugs have changed the lives of people with epilepsy for the better, more perhaps than any other treatment, before or since, and deserve to be celebrated. With the possible exception of phenytoin, the antiepileptic properties of these drugs were detected largely by chance. Each though each was a child of its time, each has had both positive and negative features. These were landmarks in reducing and ameliorating seizures as a symptom of epilepsy, but are not a cure of the disease.
The Dark Side of Epilepsy
Authors: Schmidt Dieter , Shorvon Simon
Published: November 2017

Epilepsy is a Janus-faced disease. It has a bright and a dark side. This chapter discusses the dark side of epilepsy that can harm and can devastate. It provides a perspective on the situation today and how this was arrived at. In about 20% of individuals, seizures once developed can never be fully controlled by drugs and for some, control takes many years or is never achieved. When severe, epilepsy will often destroy health and shorten life. Sudden unexpected death in epilepsy is a dark reality. Treatment of severe epilepsy is sometimes denied, delayed, or inappropriately applied, with devastating consequences; mistreatment, over-treatment, or under-treatment all occur. Modern drugs and devices for uncontrolled seizures often offer a poor value proposition. Millions of people are taking drugs that do not help them, have had operations which have failed to stop the seizures, or have had scans or other tests that carry no benefit. Fraud and scientific misinformation are other shadows which inhabit the dark corners of epilepsy.
Modelling health state valuation data
Authors: Brazier John , Ratcliffe Julie , Salomon Joshua A. , Tsuchiya Aki
Published: November 2017

This chapter examines the technical issues in modelling health state valuation data. Most measures of health define too many states to directly value all of them (e.g. SF-6D defines 18,000 health states). The solution has been to value a subset and by using modelling to predict the values of all states. This chapter reviews two approaches to modelling: one using multiattribute utility theory to determine health values given an assumed functional form; and the other is using statistical modelling of SF-6D preference data that are skewed, bimodal, and clustered by respondents. This chapter examines the selection of health states for valuation, data preparation, model specification, and techniques for modelling the data starting with ordinary least squares (OLS) and moving on to more complex techniques including Bayesian non-parametric and semi-parametric approaches, and a hybrid approach that combines cardinal preference data with the results of paired data from a discrete choice experiment.
Measuring and valuing health: an international perspective
Authors: Brazier John , Ratcliffe Julie , Salomon Joshua A. , Tsuchiya Aki
Published: November 2017

The institutionalized demand for cost-effectiveness evidence in low- and middle-income countries—where this sort of information is arguably even more urgently required—has yet to gain traction to the same extent that it has in various countries in the industrialized world. There are several important exceptions to this general observation, and these may signal a rising interest in undertaking and applying cost-effectiveness analysis (CEAs) in developing countries. The disability-adjusted life year (DALY) is an alternative to the QALY that has been favoured in much of the cost-effectiveness work in developing countries; and extends the discussions of key issues in the definition, description, and valuation of health to address some of the added considerations demanded by cross-cultural applications of the methods and tools that are the focus of this book.
Introduction to “Pluralism, incommensurability, and scientific change”
Authors: Kendler Kenneth S.
Published: November 2017

Chapter 1 is an introduction to Chapter 2, which covers views on the nature of scientific change (continuous or discontinuous; cumulative or revolutionary) and about the role of external considerations in science (corruptive or necessary), and how they depend on prior views about the nature of scientific knowledge. It sketches the principal epistemological ideas of logical empiricism, holism, and contextualism and outlines the attitudes toward change and external influence each licenses. The licensed attitudes are illustrated by reference to contemporary research on human aggression.
Biography of a brain structure: studying the diencephalon as an epistemic object
Authors: Bovet Emilie
Published: November 2017

Chapter 14 discusses the study of a hypothesis representative of the numerous attempts of psychiatry to understand brain dysfunctions. Elaborated during the first half of the twentieth century, the “diencephalic hypothesis” illustrates the quest for scientific legitimacy of psychiatry before the “discovery” of psychoactive drugs. The first aim is to show how physiology, endocrinology, neurology, and neurosurgery have influenced psychiatrists in their consideration of the mind–brain interaction, in their clinical practice and experimental researches. The second aim is to shed light on the theoretical continuity between the period preceding the “revolution” of psychoactive drugs and the one that follows it, a continuity that contrasts with the idea of a sudden transition conveyed by the more classical works. Finally, this approach raises the current stakes surrounding the birth of the psychiatric neurosciences, by inscribing them in a history based on questionings prior to the development of the neurosciences.
The development of psychoanalysis in the context of American psychiatry
Authors: Michels Robert
Published: November 2017

Chapter 20 covers how psychoanalysis is interested in human behavior and mental life, but not particularly in psychopathology. It also discusses how it originated in nineteenth-century medicine and neurology, not psychiatry, and how, by the mid twentieth century, it dominated American psychiatry. This came to an end with the clinical success of psychopharmacology, the growth of neuroscience, and the failure of psychoanalysis to develop a research tradition.
The nature of nature
Authors: Turkheimer Eric
Published: November 2017

Chapter 26 covers how Sir Francis Galton was the first to apply the Shakespearian phrase “nature and nurture” to human individual differences. The so-called nature–nurture debate began as a question of whether differences among people could be attributed to in-born characteristics or environmental characteristics. Galton predated both scientific understanding of genetics and contemporary conceptualizations of behavior, but in the century that followed it was learned that: (1) the most general answer is, “both”, (2) genetic differences were more pervasive and powerful than had been anticipated, and (3) neither genetic nor environmental variance in behavior can be readily analyzed into specific mechanisms of behavior. The completion of the Human Genome Project at the turn of the current century focused attention on how the nature–nurture question had itself evolved: modern questions of nature and nurture are no longer about discriminating genetic and environmental sources of human differences, but are instead about seeking developmental mechanisms of behavior that encompass genetic and environmental inputs.
Is it time for a “Copenhagen interpretation” in behavioral genetics?
Authors: Zachar Peter
Published: November 2017

Chapter 27 is a commentary on chapter 26, which discusses the nature of nurture, and covers the ideas and concepts surrounding Galton, nature–nurture, twins, heritability, molecular genetics, biological determinism, Huntington’s disease, divorce, personality, and biological explanation, and asks if a “Copenhagen interpretation” of behavioral genetics may be appropriate in the future.
The construction of a diagnosis is not a scientific issue
Authors: Michels Robert
Published: November 2017

Chapter 42 is a commentary on Chapter 41, which covers an ‘insiders’’ history of premenstrual dysphoric disorder and a case study of the interactions between science and extra-scientific processes involved in the construction of nosological categories of psychiatry, and how the construction of a diagnosis is not a scientific issue.
Diagnosis and classification of axial spondyloarthritis
Authors: van Gaalen Floris , van der Heijde Désirée , Dougados Maxime
Published: November 2017

Axial spondyloarthritis (axSpA) is a potentially disabling chronic inflammatory disease affecting the spine and sacroiliac (SI) joints. Lead symptoms are chronic back pain and stiffness. The disease is called radiographic axSpA or ankylosing spondylitis (AS) when, on plain radiographs, bone changes consistent with sacroiliitis are present. When no evidence of sacroiliitis is seen on radiographs, it is called non-radiographic axSpA. In such cases, diagnosis is made based on evidence of active inflammation of SI joints on magnetic resonance imaging (MRI) and clinical and laboratory features, or a combination of clinical and laboratory features only. Apart from affecting the spine and SI joints, axSpA may involve peripheral joints (e.g. knee, ankle) and manifest in extra-articular manifestations, for example uveitis, psoriasis, and inflammatory bowel disease. In this chapter, diagnosis and classification of axSpA is discussed, including use of MRI in detecting sacroiliitis and the difference between clinical diagnosis and disease classification.
Infection and spondyloarthritis
Authors: Leirisalo-Repo Marjatta , Carter John D.
Published: November 2017

Spondyloarthritis (SpA) is the designation encompassing a group of inflammatory diseases with several features in common. The patients have mono- or oligoarthritis with or without inflammatory back symptoms. Distinctive extra-articular inflammatory symptoms also characterize the diseases. The diagnostic subgroups in the SpA family include reactive arthritis (ReA), ankylosing spondylitis (AS), arthritis associated with inflammatory bowel disease (IBD), psoriasis arthritis (PsA), and some forms of juvenile-onset arthritis. These diseases share a strong association with a genetic marker, HLA-B27, absence of rheumatoid factor, tendency to family aggregation, and frequently occurring extra-articular manifestations. This chapter discusses the role of infections, either as triggering of the disease, most evident in the case of ReA, or as possibly contributing factors in the development of chronic forms of SpA and AS.
Clinical features
Authors: Khan Muhammad Asim
Published: November 2017

The leading chronic progressive inflammatory disease of the sacroiliac joints and the spinal column, traditionally known as ankylosing spondylitis (AS), is a relatively common but insidious rheumatic disease that can cause progressive limitation of physical function. It is a prototype of related forms of arthritis, grouped under the term spondyloarthritis that is subdivided into predominantly axial and predominantly peripheral forms. This chapter details the clinical features of axial spondyloarthritis, a term that encompasses ankylosing spondylitis. There is a predilection for the inflammation to affect sites where the tendons and ligaments attach to the bones (entheses) and can result in gradual and progressive spinal ankylosis, with resultant physical deformity. The disease may present with a wide spectrum of clinical features, both articular and extra-articular, and can be difficult to diagnose in early stages.
Clinical outcomes
Authors: van Tubergen Astrid , Landewé Robert
Published: November 2017

In general, axial spondyloarthritis (axSpA) follows a chronic course, requiring regular medical care and monitoring. The outcome of axSpA may vary substantially due to heterogenic presentation. For both research and clinical practice, it is important to have relevant, reliable, validated instruments for measuring outcome, to evaluate patients in a standardized way and capture all disease aspects. The Assessment in SpondyloArthritis international Society has developed core sets and instruments to measure these domains, and recommends only the most important domains being measured with best available methods. This chapter provides an overview of the most important outcomes in axSpA and most commonly used instruments to measure these. Additional measures frequently used but not (yet) included in the core set are addressed, and several sets of response criteria applied in axSpA research described. This chapter also provides guidance in which setting (research versus practice) and with which frequency these measures can be used.
Treatment: biologics
Authors: Braun Juergen , van der Horst-Bruinsma Irene E.
Published: November 2017

According to classification criteria, the spectrum of spondyloarthritis (SpA) covers axial SpA (axSpA), which includes non-radiographic axSpA and ankylosing spondylitis, and peripheral SpA, which overlaps with psoriatic arthritis. Management recommendations for many forms of SpA have been recently published. Treatment of patients with axSpA with active disease starts with a sufficient dose of non-steroidal anti-inflammatory drugs (NSAIDs) for at least 4 weeks and preferably longer, in combination with exercise. In case of peripheral SpA, several disease-modifying antirheumatic drugs can be given, but these are not efficacious in axial disease. In case of insufficient response to NSAIDs for axSpA, biologic treatment can be added. The biologics most commonly used are TNF-blocking agents, but some other biologic agents seem to be beneficial in axial diseases as well, such as secukinumab (an IL-17 blocker). However, these new drugs have not yet been approved for axSpA at the time of writing this chapter.
The gaps in translating biomedical advance into patient benefit
Authors: Barker Richard
Published: November 2017

There are no less than five major gaps in translation in the long journey from discovery to practical patient benefit. Insufficient understanding of disease mechanisms (T0), limited skills and motivation in turning lab discoveries into potential products (T1), huge wastage in bringing promising products to market (T2), disappointingly slow adoption by doctors and adherence by patients (T3), and failure to learn from past experience (T4): all cripple the productivity of life sciences. T2 is a particular challenge, especially in medicines, with a high attrition rate in costly clinical trials and increasing difficulties in persuading health technology assessment (HTA) agencies of the added-value of new technologies, combined with HTA differences across countries. Major cultural barriers between academia, practical medicine, and industry make matters worse, as mismatched incentives and mutual suspicion impede collaboration. The net result is poor yield at every stage in the innovation process and therefore very poor translation overall.
Lessons from the last 20 years
Authors: Barker Richard
Published: November 2017

A review of a dozen case examples of pharmaceutical innovation—from HIV to stomach ulcers—and others from vaccines, diagnostics, and medical devices give many pointers to the way forward to more productive and sustainable medical innovation. A sense of urgency, strong patient and public engagement, regulatory flexibility, cross-sector collaboration, and creativity on payment mechanisms all need to be built need to our new models, as we move into an era of precision medicine. We can also learn from other industries—from aerospace to IT—greater innovation around increased cost-effectiveness.
Achieving future impact
Authors: Barker Richard
Published: November 2017

To propel change forward we need not just a good sense of direction but also a sense of the prize, for patients and the health system, if we are successful. A wide range of new technologies, from technologies now coming into our hands, from gene editing to machine learning, have the potential to empower precision medicine to overcome some of mankind’s most intractable challenges: cancer, inherited diseases, aging, dementia—among many others. Taken together, the changes we propose to the innovation process could bring at least an order of magnitude greater net patient benefit over the lifetime of products, as a result of faster development, better targeting, more consistent reimbursement, swifter adoption, and better utilization.
Meningitis and meningococcal disease
Authors: Ghebrehewet Sam , Conrad David , Marsh Gill
Published: November 2017

This chapter explores the various causes of meningitis and focuses on meningitis caused by Neisseria meningitidis, which can also result in other invasive illnesses (meningococcal disease, e.g. meningococcal septicaemia/meningococcaemia). Background information on the epidemiology and clinical features of meningococcal disease, the steps and principles that need to be followed for timely implementation of public health actions (antibiotic chemoprophylaxis, Men B; Men C; Men ACWY vaccination, and public health advice) in order to prevent secondary cases following the notification of a single case or cluster in an educational setting (nursery) are discussed. Furthermore, potential public health action(s) that can be considered in dealing with cases of meningococcal disease in different circumstances/situations are covered.
Tuberculosis
Authors: Afza Musarrat , Petrovic Marko , Ghebrehewet Sam
Published: November 2017

This chapter covers two case studies and scenarios: a case of pulmonary tuberculosis (TB) in a college student; and a case of laboratory-confirmed Mycobacterium bovis in an adult with inflammatory bowel disease. The pulmonary TB case resulted in a wider investigation and contact tracing as the case attended college while symptomatic. The Mycobacterium bovis resulted in wider workplace and hospital contact tracing through convening an Incident Control Team. Background information on the epidemiology and clinical features of TB and the public health response to TB in educational, healthcare, and occupational settings are discussed. Case definitions, and a detailed risk assessment, with clear description of close contacts, priority groups, and the required public health actions, are described. ‘Top tips’ are given, to provide practical tips for the reader to think through the public health management of TB, and ‘tools of the trade’ list the laboratory and epidemiological components of the investigation.
Flooding and health: Immediate and long-term implications
Authors: Bone Angie , Wilton Alan , Stewart Alex G.
Published: November 2017

Flooding can happen at any time of year and anywhere in the UK, not just in communities living near rivers or the coast. As our climate warms, flooding is expected to occur more frequently, through a combination of sea-level rise and increasing rainfall. As floods are highly dependent on location and context, and the impacts are often complex, sustained, and diverse, a well-coordinated multi-agency plan and response is required. Flooding has extensive and significant impacts on health and wellbeing, including immediate effects (e.g. drowning, injuries, carbon monoxide poisoning) and delayed effects (e.g. mental health issues). The role of Health Protection is to provide scientific and technical advice to responders, public health communications, health surveillance, and to maintain its own business continuity. This chapter sets out the basic facts around flooding and health, illustrating the issues, actions, misconceptions and challenges during the acute response and longer-term clean-up and recovery phases.