bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetics of Pediatric Psychiatric Disorders
Authors: De Rubeis Silvia , Trelles M. Pilar , Buxbaum Joseph D.
Published: December 2017

With the advent of genome-wide methods to identify genes and loci contributing to risk for complex disorders, there has been an explosion of findings in pediatric psychiatric disorders. We provide a brief primer on recent genome-wide approaches and on key concepts that are important for the understanding of genetic findings in the field of psychiatry, with a focus on pediatric psychiatric disorders. We summarize how common and rare genetic variation, associated with either modest or high risk, contributes to the risk architecture of pediatric psychiatric disorders. As we review these approaches and concepts, we highlight salient examples from these disorders and connect to other neurobiological and clinical concepts discussed in other chapters in this section. This overview also provides background to clinical genetic reports, which are now being used more and more frequently for unexplained neurodevelopmental disorders.
Animal and Cellular Models of Pediatric Psychiatric Disorders
Authors: Drapeau Elodie , Harony-Nicolas Hala , Crawley Jacqueline N.
Published: December 2017

The study of childhood psychiatric disorders is especially challenging, not only because of the difficulties in obtaining relevant human samples but also because of ethical considerations regarding the ability of children to provide informed consent. Models that can be experimentally manipulated are therefore indispensable to study those disorders. Traditionally, biological psychiatry research has extensively employed animal models and characterizations of rodent behavior. More recently, induced pluripotent stem cells (iPSCs), and induced differentiation of iPSCs into different types of brain cells have offered new alternative strategies to elucidate mechanisms underlying cellular processes. Regardless of how they are created, optimal models should demonstrate face validity, construct validity, and predictive validity to be considered most relevant. This chapter highlights the major animal and cellular models currently used in the research of childhood-onset psychiatric disorders.
Neurobiology of Attention Deficit Hyperactivity Disorder
Authors: Faraone Stephen V. , Bhide Pradeep G. , Biederman Joseph
Published: December 2017

Attention deficit hyperactivity disorder (ADHD) is a prevalent, early-onset and persistent disorder of inattention, hyperactivity, and impulsivity. The mechanisms of action of ADHD medications, neuroimaging studies, and studies of monoamine systems and animal models suggest that dysregulation of catecholaminergic neurotransmission in cerebellar-corticostriatal circuits plays a key role in the pathophysiology of ADHD. The efficacy of ADHD medications likely arises from their differing profile of effects on (a) dopaminergic and noradrenergic systems and (b) the localization of these effects in prefrontal cortex and striatum. ADHD has a very high heritability, and although molecular genetic studies have found no causal common DNA variants yet, they have found strong evidence that rare duplications and deletions are risk factors for ADHD. Environmental risk factors, especially those that impact early neurodevelopment (i.e., exposure to cigarette smoking and alcohol during pregnancy), also influence susceptibility to ADHD.
Novel Approaches for Treating Pediatric Psychiatric Disorders
Authors: Prasad Supritha , Cook Edwin H.
Published: December 2017

Multifactorial mechanisms, including varying degrees of polygenic risk, contribute to most child onset psychiatric disorders. Methods to better understand the biological impact of inherited low-risk variation are emerging, and these studies may be useful to develop novel treatments for childhood onset psychiatric disorders. In some neurodevelopmental disorders, specifically autism spectrum disorder (ASD) and intellectual disability (ID), recurrent spontaneously mutated genes have been identified. This leads to the current focus on individual, high-risk targets (e.g., SHANK3, FMR1, MECP2, CHD8) for development of novel treatments. This chapter summarizes and begins to compare neurobiological data from several distinct single gene disorders as a means to guide further therapeutic development based on overlapping pathways of interest.
DSM-5 Overview and Goals
Authors: Regier Darrel A. , Morris Sarah E. , Schultz Susan K.
Published: December 2017

This chapter provides an overview of the developmental history of the DSM-5 and its relationship to the ICD-11 and the NIMH Research Domain Criteria (RDoC) research initiative. The emergence of differences in genetic processes and brain structure and function associated with psychiatric symptoms and disorders, as well as the development of advanced statistical approaches for conducting integrative analyses of biological correlates, phenomenological symptoms, and trait characteristics, has advanced a more complex approach to mental disorder diagnosis and classification. Categorical diagnoses of specific mental disorders are seen in a spectrum context as having porous rather than strict boundaries, with a future goal of diagnostic conceptualizations that incorporate more dimensional measures of pathological symptoms as well as neurobiological mechanisms.
The Present and Future of Psychiatric Diagnosis
Authors: Hyman Steven E.
Published: December 2017

Psychiatric disorders are currently diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders and the closely related International Classification of Diseases. Both diagnostic classification schemes are descriptive and based on a collection of signs and symptoms associated with a given disorder. The fundamental weakness of the schemes is that they are not based on the underlying genetic or neurobiological etiology or pathophysiology of a disorder which of course remain unknown for all common psychiatric syndromes. As more is learned about the biological basis of a mental disorder it will be possibly increasingly to build more accurate diagnostic schemes with greater prognostic and treatment validity.
The Nimh Research Domain Criteria Project
Authors: Cuthbert Bruce N.
Published: December 2017

The Research Domain Criteria (RDoC) project grew from recognized deficiencies in currently used diagnostic schemes for mental illness, such as the Diagnostic and Statistical Manual of Mental Disorders (DSM). While the latter is based on a series of signs and symptoms of illnesses that can co-occur in groups of individuals, without consideration of underlying biological factors, RDoC is based on the increasing ability to relate normal as well as abnormal behavior to particular molecules and circuits in the brain across animal species and humans. Behavioral domains include negative valence systems (e.g., fear and anxiety), positive valence systems (e.g., reward and motivation), cognitive systems, social processes, and arousal and regulatory systems, several of which might be affected in a given DSM disease classification. RDoC is seen as a step toward a “precision psychiatry,” where increasing knowledge of the genetic, molecular, cellular, and circuit basis of mental illness will yield biologically based diagnoses that offer important pathophysiological, treatment, and prognostic implications.
Demography of global ageing
Authors: Bloom David E. , Mitgang Elizabeth , Osher Benjamin
Published: December 2017

Individuals aged 65 years and older currently make up a larger share of the population than ever before, and this group is predicted to continue growing both in absolute terms and relative to the rest of the population. This chapter begins by introducing the facts, figures, and forecasts surrounding the ageing of populations across different countries at varying levels of development. In light of these trends, we examine challenges facing greying societies through the lenses of health, economics, and policy development. The chapter concludes with a selection of adaptable strategies that countries might consider to mitigate the strain—and to harness the full potential—of ageing populations worldwide.
History taking and physical examination
Authors: Ribera-Casado José M.
Published: December 2017

In geriatric medicine, history taking and physical examination differ from the way that these clinical skills are traditionally recommended for younger patients. The definitive approach to a full diagnostic appraisal is through a ‘comprehensive geriatric assessment’. This takes time, and may need modification of the use of language and of the physical setting. Social situation, physical and mental function, and bioethical personal values are essential components of this approach. The findings from a careful, systematic, and detailed physical examination can never be replaced by biological or clinical tests. Physical findings typical for some clinical conditions in younger patients may be absent in older patients and some significant findings are particular to older patients. Certain aspects of assessment tend to be more commonly overlooked, including full medication history including self-medicating habits, nutritional status, and evidence suggesting physical, sexual, or mental abuse.
Principles of medication management
Authors: Le Couteur David G. , McLachlan Andrew J. , Hilmer Sarah N.
Published: December 2017

Older people use numerous medications, yet the evidence for effectiveness in old age is often limited while the evidence for medication-related harm is substantial. Issues common in older people such as multimorbidity, polypharmacy, frailty, dementia, and terminal illnesses influence the decision to prescribe or deprescribe. Age-related changes in drug disposition, coupled with concerns about adverse drug reactions often necessitate lower maintenance doses. Medical ethics and the principles of pharmacokinetics and pharmacodynamics provide overarching frameworks to tailor evidence-based medicine and single disease guidelines to the individual needs and goals of older and frail people. Close monitoring combined with the assumption that any symptom can be medication-related are key clinical skills required for the ongoing optimization of medication use in older people.
Geriatric patients in the emergency department
Authors: Melady Don , Goldlist Barry J.
Published: December 2017

This chapter addresses strategies for closing the ‘quality gap’ between the needs of complex older patients presenting to an emergency department (ED) and what current EDs mostly provide. It reviews historical reasons that the current system often fails to address the multiple and multifactorial needs of an older person in the ED. It explores domains of care—complex and atypical presentations, an awareness of polymorbidity, polypharmacy, falls, cognitive impairment, and end-of-life issues—that are specific to the older ED patient. It suggests opportunities for quality improvement in the essential components of a senior-friendly ED, summarizing some of the changes to staffing, education, policies, procedures, and physical design that prioritize the needs of older patients. It identifies the importance of the ED’s role in the continuum of care and opportunities for improving transitions of care involving the ED.
The emergence of ageing phenotypes and multisystem decline
Authors: Fabbri Elisa , Zoli Marco , Ferrucci Luigi
Published: December 2017

Ageing is characterized by multisystem morphological and physiological changes, which occur very heterogeneously across different individuals. The resulting phenotype is so dynamic and complex that its comprehensive description is still a critical area of research in gerontology. The progressive multisystem instability and deterioration that characterize ageing are, however, very heterogeneous among different individuals. Many researchers believe that such instability is the result of stochastic accumulation of damage and loss of function rather than the consequence of precisely controlled and genetically programmed processes. In approaching such complexity, we have proposed that the phenotypes of ageing can be clustered in discrete interactive domains, whose impairments can serve as proxy measures of the rate of ageing, since they strongly relate to loss of resilience, development of multimorbidity, and occurrence of geriatric syndromes in older adults.
Anorexia of ageing
Authors: Landi Francesco , Martone Anna Maria , Calvani Riccardo , Marzetti Emanuele
Published: December 2017

Anorexia of ageing, defined as the loss of appetite and/or decreased food intake in late life, is a notable paradigm of geriatric syndromes. The latter expression originated because the multifaceted clinical conditions that are common among frail older persons are not easily grouped into specific diseases or ‘traditional’ syndrome categories. Anorexia is indeed highly prevalent and is recognized as an independent predictor of morbidity and mortality in different clinical settings. Even though anorexia is not an unavoidable consequence of ageing, advancing age often promotes its development through various mechanisms. Age-related changes in lifestyle, disease conditions, as well as social and environmental factors have the potential to directly affect dietary behaviours and nutritional status. Anorexia of ageing is indeed associated with many of the syndromes and effects that occur when the accumulation of health impairments in multiple systems combine to make older persons more vulnerable to internal and/or external stressors.
Protein and energy requirements in health and illness
Authors: Bauer Jürgen M. , Diekmann Rebecca
Published: December 2017

The preservation of functionality in elders is closely associated with their nutritional status. In this context it is pivotal for them to meet their nutritional requirements, which vary according to their individual needs. The latter are influenced to a large degree by activity level and comorbidity. Most older individuals will cover their energy needs in the range 25–30 kcal/kg body weight (BW) per day, but in extreme states like hyperkinetic dementia, the daily energy requirement may amount to 40 kcal/kg BW per day. To achieve optimal protein intake, older persons will need more protein per kg BW than the World Health Organization (WHO) recommendation of 0.8 g/kg BW per day, which was not varied according to age. For slowing the associated decline in muscle mass and bone quality, 1.0–1.2 g protein/kg BW per day is recommended. In older individuals with relevant comorbidity, even higher protein intake is advisable.
Metabolic syndrome
Authors: Maggi Stefania , Crepaldi Gaetano
Published: December 2017

Two of the major determinants of rising healthcare costs in Western society are represented by population ageing, which is accompanied by a parallel increase in age-associated diseases and disabilities, as well as by obesity and its related comorbidities. Many studies have shown that selected risk factors such as impaired glucose tolerance, atherogenic dyslipidemia, and hypertension co-occur to a greater degree than that expected by chance alone in obese individuals (especially in those with central obesity). Their co-occurrence has been defined as ‘metabolic syndrome’, a multifactorial disease of substantial heterogeneity, a major risk factor for type 2 diabetes mellitus, atherosclerotic cardiovascular disease (CVD) and, in the older population, also for cancer, cognitive decline, functional dependence, depression, low quality of life, and mortality. Identifying and treating metabolic syndrome (MS) is thus of vital importance because it could lead to a significant decrease in the burden of morbidity and mortality in older patients.
Osteoporosis in the oldest old
Authors: Rizzoli René
Published: December 2017

Osteoporosis and frailty greatly increase the risk of fracture. Hip fractures are the most serious osteoporotic fractures, with increased risk of mortality. In most countries, the majority are over 80 years old. Large rises on hip and other fragility fracture rates are predicted for much of South America and Asia in the coming decades. The survivors have a high risk of sustaining another major fracture and face deterioration in their quality of life and high risk of dependency. Optimal protein and calcium intakes, and vitamin D supplies, together with regular weight-bearing physical exercise are the cornerstones of fracture prevention. Evidence for antifracture efficacy of pharmacological interventions relies on randomized controlled trials in postmenopausal women between the ages of 50 and 80 years and the evidence of antiosteoporotic efficacy in the oldest old has come primarily from subgroup analyses.
Peripheral neuropathies and motor neuron disorders
Authors: Mathis Stéphane , Bouche Pierre , Vallat Jean-Michel
Published: December 2017

Peripheral nervous system disorders are common in older people. Most peripheral neuropathies are secondary to metabolic (diabetes) or toxic causes (medications, alcohol), but several other aetiologies are possible, requiring clinical, electrophysiological, biological, and sometimes pathological (nerve biopsy) examinations to make the right diagnosis and instigate effective treatments. However, despite using this strategy, no cause is found in some axonal polyneuropathies, leading to the concept of chronic idiopathic axonal polyneuropathy (CIAP). Amyotrophic lateral sclerosis (ALS) affects the peripheral nervous system, but is also characterized by central nervous system involvement: it is a strictly motor disorder affecting both the first and second motor neurons, usually presenting during the sixth or seventh decade. This rapidly progressive, still incurable neurodegenerative disease leads to death in all cases.
Headaches and facial pain
Authors: Weatherall Mark
Published: December 2017

Headache and facial pain generally become less frequent as people age, but nonetheless remain common problems in the older population, with a one year prevalence of about 50%. Primary headache disorders such as tension-type headache, migraine, or cluster headache may present de novo, or persist into old age; atypical features may become more common, and attacks more difficult to treat. Rarer primary disorders causing headache or facial pain, such as trigeminal neuralgia, short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome), hypnic headache, and primary cough headache predominantly or exclusively affect older people, but secondary headache and facial pain disorders are likely to account for a greater percentage of diagnoses. Such disorders may be benign, such as cervicogenic headache, or potentially very serious, such as giant cell arteritis or subdural haematoma.

Assessment and management of pain in older people may be challenging.
Seizure disorders and management
Authors: Schachter Steven C.
Published: December 2017

Epilepsy is common and in developed countries with ageing populations, the highest incidence and prevalence of epilepsy is in older people. The classification of seizure types is based on the patient’s or an observer’s description of the seizure. Most new-onset seizures in elderly persons arise from a focal area of the brain, often causing vague and non-specific symptoms or observable behaviours such as motionless staring, blackouts, delirium, disorientation, or limb jerking. The goals of treatment are to fully control seizures without bothersome side effects. Antiepileptic drugs (AEDs) are the mainstay of therapy; selecting an AED is based on a number of factors. Therapy should be initiated with a low dose and slowly titrated as needed. This chapter reviews the epidemiology, clinical evaluation, and treatment considerations for new-onset epilepsy in older people.
Primary and secondary prevention of stroke
Authors: Manning Lisa , Lam Man Yee , Robinson Thompson G.
Published: December 2017

Stroke is one of the leading causes of mortality, morbidity, and disability worldwide. Stroke and transient ischaemic attack survivors are at risk of recurrent stroke, which is often more severe and disabling. Despite the success in acute treatment and rehabilitation of stroke, prevention remains the most effective way to reduce the global burden of the disease. Since preventative strategies have early effectiveness, prompt recognition of symptoms, specialist assessment and diagnosis, and initiation of these secondary prevention strategies are of utmost importance in stroke prevention. This chapter provides an overview of current primary and secondary stroke prevention strategies, highlighting the importance of rapid recognition, urgent specialist care, and evidence-based interventions, which are the cornerstones of effective management.
Neurological rehabilitation
Authors: Kwan Joseph S. K. , Tse Mona M. Y. , Li Leonard S. W.
Published: December 2017

Neurological rehabilitation aims to help people regain functional independence from physical and cognitive disabilities caused by neurological injuries or diseases, improving their participation in the society and quality of life. Among older patients, the more common need for neurological rehabilitation arises from acute stroke, traumatic brain injury, or spinal cord damage. There has been a recent paradigm shift in the approach of neurological rehabilitation towards promoting neural reorganization, restructure and modification of brain activity patterns (neuroplasticity). Stroke patients benefit from organized interdisciplinary care within a comprehensive stroke unit, followed by early supported discharge in the community. Early intensive therapy and prevention of complications such as infections are the key components of acute neurological rehabilitation. In the post-acute period, a problem-oriented approach using evidence-based strategies can enhance neuroplasticity and patient outcome. Special attention is needed for traumatic brain injury and spinal injury, younger patients, and those with neurocognitive dysfunction.
Pharmacological interventions in mild cognitive impairment and dementia
Authors: Hugon Jacques , Paquet Claire
Published: December 2017

Alzheimer’s disease (AD) and other dementias are a major public health concern in many countries because of population ageing. The aetiologic causes of most of the dementias are unknown and recent pharmacological interventions are based on hypotheses such as the ‘amyloid cascade hypothesis’ for AD. Drugs can be divided between symptomatic treatments and disease-modifying drugs. So far regulatory authorities have only approved choline esterase inhibitors (ChEIs) and memantine in AD. It is postulated that the brain lesions in this disease occur 10–15 years before the first clinical signs. New clinical trials are now also including patients with mild cognitive impairment, a stage which often precedes dementia. Primary and secondary outcomes incorporate neuropsychological evaluations but also biomarker assessments such as positon emission tomography (PET) imaging and cerebrospinal fluid (CSF) measurements. This chapter focuses on current available therapies and recent or ongoing clinical trials in mild cognitive impairment and dementias.
A new model of care for patients with dementia: the Japanese initiative for dementia care
Authors: Maki Yohko , Sakurai Takashi , Toba Kenji
Published: December 2017

Facing the unprecedented ageing society, Japan’s contribution to the world should be to lead worldwide discussion on dementia care. This chapter introduces the Japanese initiatives for dementia care. For realization of a society where people with dementia live well, the new concept of ‘prosocial relationship-based care’ for dementia has been introduced as the ethical background; community members are expected to reach out helping hands to each person with dementia to restore their participation in society. Based on this basic concept and the long-term care insurance system, various measures related to primary, secondary and tertiary preventive approaches for dementia have been promoted to achieve appropriate and seamless coordination of medical and long-term care. To establish prosocial relationships, it is critical to promote cooperation among various stakeholders, and develop community networks and social resources.
Older people with substance problems
Authors: Crome Ilana , Rao Rahul (Tony)
Published: December 2017

Not only is the number of older people in our society is increasing, but their use of substances is rising. All substances should be considered (i.e. alcohol, tobacco, polypharmacy, illicit drugs, over-the-counter medication, substances obtained over the internet, and misuse of prescription drugs). Associated mental health and physical health difficulties need to be viewed in light of the combination of substances and interactions with clinical conditions. The service delivery system is unprepared partly due to an invisible epidemic fuelled by numerous factors including ageism, denial, stereotypes, and non-specific symptoms. A thorough ongoing routine assessment of substance use is the keystone of a treatment management plan. Older people willing to be engaged in a multidisciplinary team treatment do have capacity to change, and outcomes are at least was positive as their young adult counterpart. There are gaps about treatment prevalence, the facilitators and barriers to treatment, including comorbid conditions.
Oral health and mouth diseases
Authors: MacEntee Michael I.
Published: December 2017

The mouth contributes to nutrition, respiration, and communications but it also contains potential pathogens that threaten other parts of the body. It is readily accessible to spot early signs of immune, endocrine, haematological, gastrointestinal, metabolic, and neoplastic disorders. Teeth are destroyed rapidly by the sugar-laden diets and poor oral hygiene that are common occurrences among residents of long-term care facilities. Moreover, the adverse effect of rampant dental caries from medications that disturb salivary flow is too often overlooked by physicians and pharmacists. Oral cancer causes more deaths than each of colorectal, gastric, prostate, and breast cancers, while oral mucositis can be an excruciatingly painful side effect of chemotherapy and radiotherapy. Overall, impairments and disabilities of the mouth and teeth influence physical and cognitive homeostasis and frailty, whereas effective management of oral disorder is an essential component of good geriatric care for successful ageing and quality of life in old age.
Malabsorption
Authors: Ducrotté Philippe , Chassagne Philippe
Published: December 2017

The clinical challenge of recognizing then treating malabsorption is crucial in older patients, in whom the consequences in terms of both morbidity and mortality are more severe. This challenge is reinforced by a frequent atypical clinical presentation delaying the diagnosis in many cases. Indeed, as in many diseases that occur in old patients, symptoms such as weight loss are often considered to be related to altered appetite or increased catabolism rather than to malabsorption. We now have substantial evidence that malabsorption in older people should not be ascribed to the ageing process and should be evaluated in the same way as malabsorption occurring in younger patients. In an older patient, there may be several contributory causes.
Constipation and faecal incontinence
Authors: Chassagne Philippe , Roca Frédéric
Published: December 2017

Constipation and faecal incontinence are the two main functional digestive disorders reported by old people. Prevalence increases with age and predominantly affects women. Both are associated with poorer quality of life. Clinical assessment of constipation including a detailed history is the best approach to identify features suggesting abnormal transit or evacuation problems. As for many geriatric syndromes, medication related effects should always be considered. Faecal incontinence is a marker of disability assessed by most activities of daily living (ADL) scales. In severe cases, faecal incontinence is also associated with high mortality rates. The main risk factor for transient faecal incontinence is the coexistence of a functional digestive disorder such as constipation (especially with faecal impaction) or diarrhoea. These two conditions must be identified since they can be improved by specific therapeutic programmes, which are usually multidimensional and multiprofessional.
Symptom assessment and management at the end of life
Authors: Van Den Noortgate Nele , Sampson Elizabeth
Published: December 2017

As people age, the number and complexity of illnesses they develop increases. Symptoms during the last year of life in older persons are often a combination of the underlying life-threatening illness and other chronic conditions. These may be complicated by psychosocial and spiritual needs, related to life events such as bereavement. Geriatric palliative medicine involves the care and management of older patients’ progressive advanced disease, for whom the aim is quality of life. It focuses on detailed geriatric assessment, relief from pain and other symptoms such as anorexia, constipation, or delirium, and also management of psychological problems including depression or anxiety. This may be more challenging in people with cognitive impairment who may not be able to express whether they are in pain or otherwise suffering. Adequate pain and symptom management at the end of life emphasizes the need for a tailored multidisciplinary approach for patients and their family.
Healthy ageing phenotypes and trajectories
Authors: Collino Sebastiano , Comte Blandine , Guillot Estelle Pujos , Franceschi Claudio , Galindo Antonio Nuñez , Dayon Loïc , Kussmann Martin
Published: December 2017

The concept of healthy ageing today is linked to the efforts of maintaining physical and mental independence, and to prevent the decline of physiological functions that are mandatory to guarantee a good quality of life. Yet, an individual’s ageing trajectory and underlying mechanisms are multifaceted and still far from understood. Hence, there is an urgent need for the further development of ageing phenotypes that can be utilized in the identification of biomarkers to characterize and predict biological age, taking into account the multiple dimensions of ageing. New technologies, often termed ‘systems biology’ approaches, are being increasingly applied to research focused on ageing populations. These technologies should enable investigators, and eventually clinicians, to (a) understand ageing metabolism in a more detailed and specific way; (b) enable the phenotypic characterization of many age-related disorders including chronic disease states; and (c) stratify older adults and the multiple comorbid conditions that may impact them.
Driving, transportation, and mobility in the older adult
Authors: Shapiro Benjamin M. , Fitten L. Jaime
Published: December 2017

Older adults drive more miles than prior generations and have mobility and transportation needs that are central to independence and well-being. While older adult crash rates have decreased due to safety improvements, those aged 80 years and older have higher morbidity and mortality from crashes due to physical vulnerabilities. Normal ageing is associated with cognitive, motor, and sensory changes that prompt healthy older adults to modify their driving. Older adults use a wide range of potentially driver-impairing medications that increase accident risk. Glaucoma, visual field changes from strokes, and other impairments assessed in the Useful Field of View test can significantly increase crash risk. Moderate and advanced dementia results in unsafe driving due to the impact on ‘process skills’, resulting in the prevailing opinion that they should not drive. However, there is no appropriate screening instrument to assess driving safety among older adults.
Physiology and metabolism of fungal pathogens
Authors: Gow Neil A.R. , Brown Alistair J.P.
Published: December 2017

The metabolism and physiology of an invading fungal pathogen determine the outcome of its interaction with the host. The pathogen must be able to assimilate nutrients to grow and colonize diverse host niches. Meanwhile, the host attempts to restrict this growth by withholding some essential nutrients, by imposing stresses, and by inducing innate immune defences. These interactions involve complex regulatory networks that ultimately dictate the equilibrium between pathogen killing and the establishment of commensal or pathogenic associations.
Fungal cell structure and organization
Authors: Read Nick D
Published: December 2017

Human pathogenic fungi produce three basic ‘cell’ types: hyphae, yeast cells, and spores. The organization and subcellular structure of these different cell types and their modes of growth and formation are reviewed. Growth and form is the consequence of how new cell surface is formed. This is generated by the delivery of vesicles to the surface which provides new membrane and the enzymes for cell wall synthesis. To generate these various cell types, the pathway of vesicle secretion to the surface has to be carefully regulated. These vesicles have to be transported through the cell by the cytoskeleton, and in filamentous cells these vesicles accumulate at a supply centre called the Spitzenkörper before docking and fusion with the hyphal apex. Ultimately, membrane is also endocytosed and recycled behind actively expanding regions of the fungal surface. These various processes are described and particular emphasis is given to the structural and organizational features of fungal cells that play roles in their pathogenesis and virulence.
Epidemiology of fungal disease
Authors: Mody Rajal K. , Cleveland Angela Ahlquist , Lockhart Shawn R. , Brandt Mary E.
Published: December 2017

Surveillance and outbreak investigations are important epidemiological tools for assessing the frequency, distribution, and determinants of infections. The primary goal of these activities is to identify measures to reduce the burden of disease. This chapter describes examples of surveillance and approaches to outbreak investigations that have formed the basis of fungal infection control measures. However, considerable knowledge gaps exist, new threats are emerging (including antifungal resistance), and healthcare advances are making more people susceptible to severe fungal infections. Expanded surveillance efforts, timely outbreak detection, and effective outbreak investigations are needed to further reduce the burden of fungal infections. This will require confronting challenges that have held back fungal disease epidemiology, including limited clinical suspicion of fungal infections by clinical providers, difficulties in diagnosing fungal infections due to suboptimal diagnostic methods, limited availability of antifungal susceptibility testing and molecular subtyping, and a lack of mandated fungal disease surveillance in most countries.
Cryptococcus species
Authors: Halliday Catriona L. , Kidd Sarah E.
Published: December 2017

Cryptococcus neoformans and Cryptococcus gattii are the principal pathogenic species within the genus Cryptococcus and the causative agents of cryptococcosis. Although rare, the incidence of infection due to other Cryptococcus species previously regarded as saprophytes, has increased over the last 40 years. Irrespective of the infecting species, infections are acquired following inhalation from the environment, causing localised or disseminated disease. The severity of disease is dependent on the organism’s virulence factors and the host’s immune response, and the clinical manifestations are indistinguishable. Accurate identification of the pathogenic species relies on rDNA sequencing
The dermatophytes
Authors: Howell Susan
Published: December 2017

Dermatophytes are unique in their ability to utilize keratin as a substrate, and this makes them the commonest cause of superficial skin, hair, and nail infection worldwide. They comprise three genera and more than 30 species, and species have evolved to be anthropophilic, zoophilic, or geophilic. Infection is acquired by contact with a source, and on skin is known as ringworm because a circular lesion with a raised scaling edge may form. Diagnosis requires microscopic examination of tissue and culture to identify the pathogen. Management of infection includes identifying the source to prevent reinfection.
Pneumocystis jirovecii
Authors: Flanagan Stuart
Published: December 2017

In humans, Pneumocystis pneumonia is caused by a yeast-like fungus Pneumocystis jirovecii. Originally called P. carinii, this organism was thought to be a protozoan; however, the discovery of chitin, β-1,3-glucan, and ergosterol in the cell wall confirmed it as a fungus. DNA analysis demonstrated that the human disease was caused by P. jirovecii, while P. carinii was found to infect rats. P. jirovecii resides in mammalian lung tissue, usually without ill effects, but in immunocompromised hosts it becomes pathogenic and causes respiratory infection. P. jirovecii has been isolated from air and pond water samples; pond water is the potential source of infection. Almost 90% of cases of Pneumocystis pneumonia occur in HIV-positive individuals with CD4 T-cell counts below 200 cells per microlitre. The infection is diagnosed by clinical history, assessment of oxygenation levels, and direct microscopy of sputum or bronchoalveolar lavage samples. Treatment requires antibiotics and HAART (highly active antiretroviral therapy) for HIV infection.
Fungal cardiovascular infections
Authors: Drake Sarah , Sandoe Jonathan
Published: December 2017

Fungal cardiovascular disease can broadly be divided into four groups: infective endocarditis (including implantable cardiac electronic devices), mycotic aneurysms, vascular graft infections, and intravascular catheter-related infections. These conditions are rare but are associated with significant morbidity and mortality, which may be in excess of 80% in certain groups of patients. Candida spp. and Aspergillus spp. account for the majority of these infections, but rare fungi may also be involved, particularly in infective endocarditis, where they are responsible for approximately 25% of cases. This chapter will cover the epidemiology, causative fungi, clinical features, diagnosis, management, and prevention of these four fungal cardiovascular conditions.
Fungal infections of the skin and subcutaneous tissue
Authors: Hay Roderick J.
Published: December 2017

Fungal infections that involve the skin range from tinea pedis or ‘athlete’s foot’, which presents no threat to life, to less common, and often life-threatening, systemic mycoses such as cryptococcosis. The superficial infections are world-wide in distribution, and are estimated to be the fourth most common of all non-fatal causes of human disability. Diagnosis is often clinical, supported where appropriate by laboratory diagnostics. However, in those cases where deep infection is possible, screening patients for other sites of infection is key to therapeutic success. Treatment for the superficial infection is often based on topical medications obtainable without prescription, whereas the systemic infections usually require the best treatment for bloodstream-disseminated forms of infection.
Fungal diseases of the ear, nose, and throat
Authors: Chakrabarti Arunaloke
Published: December 2017

Fungal infection of the ear (otomycosis), nose (fungal rhinosinusitis), and throat (oropharyngeal candidiasis) are common diseases. Fungal laryngeal diseases and invasive otomycosis & acute fungal rhinosinusitis are much less common and occur in immunosuppressed hosts, including those with diabetes. Aspergillus and Candida spp. are the commonest causes of otomycosis, whilst Aspergillus spp. predominate in sinus disease, with members of the Mucorales also causing serious invasive infections. Management of the non-invasive conditions can be difficult, and otomycosis and rhinosinusitis often become chronic. Invasive disease usually requires surgical intervention along with appropriate antifungal therapy. Acute invasive fungal rhinosinusitis has a mortality of approximately 50%.
Fungaemia and disseminated infection
Authors: Lester Rebecca , Rex John
Published: December 2017

Invasive fungal disease can present without localization or obvious target organ involvement. These disseminated mycoses occur predominantly in patients who are immunocompromised, particularly from haematological malignancy and HIV. Candidiasis and aspergillosis are the commonest forms of disseminated fungal infection worldwide, but an increasing number of non-Candida yeasts and non-Aspergillus moulds have emerged as important causes of invasive disease in recent years. Endemic fungi such as Histoplasma capsulatum are important causes of invasive disease within limited geographic regions. Fever is the commonest manifestation of disseminated fungal infection, but other clinical features such as cutaneous manifestations may point to a specific diagnosis. Definitive diagnosis relies on the detection of fungi in tissue or blood, but serological tests can augment diagnosis in some infections. Mortality from disseminated fungal disease is high and prompt initiation of antifungal therapy—where invasive disease is suspected—is essential.
Genito-urinary fungal infections
Authors: Sobel Jack D.
Published: December 2017

The predominant fungal causes of genitourinary disease are Candida spp.; other fungal genera are uncommon pathogens in both sexes. Vulvovaginal candidiasis affects millions of women worldwide—and includes acute sporadic, recurrent, and chronic syndromes—and considerable progress has been made in understanding its pathophysiology and hence the best therapy. Therapeutic options are still limited, however, and misdiagnosis is common. In contrast, urinary tract candidiasis reflects an entirely different pathogenesis and clinical expression affecting a predominantly hospital-based older population. Candida organisms are extremely difficult to eradicate from often complicated urinary tract infections. Non-Candida fungal species reach the kidney and prostate by the bloodstream rather than the ascending route taken by Candida spp. In women, not infrequently, there is simultaneous lower genital tract and urinary tract infection, requiring attention to both systems.
Fungal eye infections
Authors: Clark Heather L. , Pearlman Eric
Published: December 2017

Mycotic keratitis is a fungal infection of the cornea that leads to severe, painful ulceration and loss of vision, and is a major cause of blindness worldwide, particularly in the developing world. Major risk factors for mycotic keratitis include ocular trauma and contact lens use. Both yeasts and moulds can cause mycotic keratitis, with the filamentous moulds of the Fusarium and Aspergillus genera the most common aetiological agents worldwide. Fungi, particularly Candida spp. yeasts, can also cause endophthalmitis—a painful, blinding infection of the posterior eye. Treatment of these infections is challenging owing to a limited arsenal of antifungal agents and highly variable susceptibility among causative fungi. Furthermore, associated inflammation contributes greatly to tissue damage and permanent blindness. Studies using experimental models of mycotic keratitis have revealed new targets for novel antifungal agents and anti-inflammatory therapies that have the potential to reduce the impact of these devastating infections.
Fungal diseases of the respiratory tract
Authors: Jacobs Samantha E. , Small Catherine B. , Walsh Thomas J.
Published: December 2017

Fungal respiratory infections are important causes of morbidity and mortality in immunocompromised patients. Invasive aspergillosis remains the most common invasive fungal infection whereas other filamentous fungi, such as Fusarium spp., Mucorales, and Scedosporium spp., are increasing in frequency, particularly in neutropenic hosts. Endemic mycoses, including those due to Histoplasma capsulatum, Coccidioides spp., and Talaromyces marneffei, are increasingly prevalent in patients with cell-mediated immunodeficiencies in respective geographic regions. Culture remains the gold standard of diagnosis but has limited sensitivity and often requires invasive procedures. Non-invasive diagnostic tests, including the serum sandwich enzyme immunoassay for the detection of galactomannan, the (1→3)-β-D-glucan assay, and molecular amplification methods have been developed to facilitate early and accurate diagnosis. Successful therapy depends upon early initiation of antifungal agents and reversal of immunosuppression. Lipid formulations of amphotericin B and newer generation triazoles including voriconazole, posaconazole, and isavuconazole have expanded the ability to treat multi-drug resistant pathogens more effectively and with less toxicity.
Fungal infections in haemato-oncology
Authors: Koehler Philipp , Cornely Oliver A.
Published: December 2017

Invasive fungal infections on haemato-oncology wards present a major challenge. Patients at risk for invasive fungal infection usually have a compromised immune system due to bone marrow failure caused by underlying disease, prolonged neutropenia after intensive chemotherapy, or immunosuppression after haematopoietic stem cell transplantation to avoid graft-versus-host disease. Three major entities—invasive candidiasis, invasive aspergillosis, and mucormycosis—account for the majority of fungal infections. Here, we describe specific host and therapeutic factors predisposing to invasive fungal infection in the haemato-oncology setting. Clinical presentation is highly variable and dependent on the underlying pathogen, organ involvement, and site of infection. Diagnosis is mainly based on radiographic imaging combined with microbiological and histopathological work-up. Various prophylaxis and treatment strategies have been developed, and the evidence for these is discussed.
Fungal infections among patients with AIDS
Authors: Denis Blandine , Lanternier Fanny , Lortholary Olivier
Published: December 2017

Fungal infections are the most common opportunistic infections occurring in HIV-infected patients, though their incidence has decreased dramatically with the introduction of combination antiretroviral therapy (cART). Most cases occur in untreated/non-compliant patients or patients whose multiple antiretroviral regimens have failed. They are a good marker of the severity of cellular immunodepression. Pneumocystis jirovecii pneumonia remains a frequent opportunistic infection in rich resource settings, and cryptococcosis a major problem in the Southern Hemisphere. In endemic areas, infections due to dimorphic fungi are an important group. An exhaustive search for dissemination should be made in HIV-infected patients—at least for those at an advanced stage of immune deficiency. Introduction of cART in combination with antifungal treatment depends on the risk of acquired immune deficiency syndrome (AIDS) progression, and on the risk of cumulative toxicity and the immune reconstitution inflammatory syndrome if introduced too early. Fungal infections remain a problem in the cART era.
Fungal infections in solid organ transplantation
Authors: James Darius Armstrong , Shah Anand , Reed Anna
Published: December 2017

Fungal infections are a significant and life-threatening complication of organ transplantation, on a global scale. Risk varies according to transplant type, with liver, lung, and small bowel transplant recipients being at particular risk. Whilst invasive candidiasis is the most common fungal infection in organ transplantation overall, aspergillosis is a particular problem in lung transplantation. In addition, a wide spectrum of fungi may cause invasive disease in organ transplantation, consequently diagnosis and treatment can be challenging. Key challenges are to understand individual risk for infection, appropriate prophylactic strategies, and molecular diagnostic approaches. Treatment options are complicated by drug–drug interactions with transplant therapy, as well as intrinsic allograft dysfunction seen in many patients. In this chapter, we review the epidemiology, risk factors, diagnosis, and management of fungal infections in solid organ transplantation.