bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification and diagnosis of headache disorders
Authors: Olesen Jes , Lipton Richard B.
Published: April 2020

Disease classification systems delineate a group of related disorders and provide operational rules for defining the boundaries among them. Diagnosis refers to the assignment of a particular individual to a particular diagnostic category. A robust disease classification system provides a framework for standardizing diagnosis, studying epidemiology, predicting prognosis, assessing treatment, and implementing therapy in practice. Disease classification is therefore crucial for both clinical practice and research.
Headache mechanisms
Authors: Charles Andrew
Published: April 2020

Headache disorders involve widespread disturbances in nervous system function, resulting in a broad array of symptoms in addition to head pain. A general understanding of these disorders requires not only an understanding of the mechanisms underlying the pain, but also of those causing symptoms that may precede, accompany, or follow the pain. Imaging and clinical electrophysiological studies provide strong evidence that rather than being primarily vascular disorders, the major primary headaches disorders are fundamentally disorders of brain excitability. Changes in the activity of the thalamus and cortex appear to be particularly important in migraine, and alterations in hypothalamic function likely play a critical role in both migraine and cluster headache. Migraine aura involves propagated waves of activity in the cortex; cortical spreading depression (CSD) in animal models provides insight in the mechanisms of these waves. Elevations of extracellular potassium and release of the excitatory transmitter glutamate appear to be critical in the initiation of CSD, whereas sustained uncoupling of the normal relationship between neural and vascular activity occurs in the wake of CSD. Headache pain may be transmitted not only by trigeminal nerves, but also by the upper cervical nerves. The trigeminal nucleus caudalis, dorsolateral pons and midbrain, periaqueductal gray, thalamus, and sensory cortex may all play important roles in headache. Increasing evidence implicates the release of neuropeptides, particularly calcitonin gene-related peptide as a primary mediator of headache. Each of these and other basic mechanisms of headache may represent distinct therapeutic targets
Migraine
Authors: Peatfield Richard , Sakai Fumihiko
Published: April 2020

The vast majority of patients presenting with headache and no physical signs will have migraine, or, less commonly, a variant such as cluster headache. Some migraine patients will have a typical visual, sensory, or speech aura, while others will have less clear-cut premonitory symptoms. A careful history will establish whether there are any atypical features that might warrant further investigation and/or suggest an alternative diagnosis. It is essential that the initial assessment ascertains the frequency and severity of the attacks, as this will determine whether analgesic or prophylactic treatment or both should be offered. The patient’s previous medication should be recorded, noting the largest doses given and the reason why each had been discontinued. Many will be overusing analgesics, particularly opiates, and these can easily lead directly to a chronic drug-induced headache. The real skill in headache management is ensuring that the patient’s history is fully and accurately recorded.
Hemiplegic migraine and other monogenic migraine subtypes and syndromes
Authors: Pelzer Nadine , Freilinger Tobias , Terwindt Gisela M.
Published: April 2020

Hemiplegic migraine (HM) is a rare monogenic subtype of migraine with aura that includes reversible motor weakness and can be either familial or sporadic. Three genes have been associated with HM. Migraine can also be part of more elaborate monogenic syndromes. When the family history includes early-onset cerebrovascular diseases and dementia, the monogenic small-vessel diseases CADASIL, RVCL-S, and COL4A1-associated syndromes should be considered. The mitochondrial disease MELAS is also associated with migraine-like and stroke-like episodes, often with a progressive nature, hearing loss and short stature. Like familial HM type 1, EA2 and SCA-6 are associated with CACNA1A mutations. All three disorders can include episodic and progressive ataxia and imaging may reveal cerebellar atrophy. Episodic hemiplegia or quadriplegia also occurs in the rare disorder alternating hemiplegia of childhood, with an age at onset before 18 months and often in association with tonic/dystonic attacks and developmental delay.
Migraine, stroke, and the heart
Authors: Sacco Simona , Carolei Antonio
Published: April 2020

Accumulating data have linked migraine to cerebrovascular and heart diseases. The relationship between migraine and stroke is complex and bidirectional. A stroke, either ischaemic or haemorrhagic, may produce symptoms mimicking a migraine attack; a migraine attack may mimic a stroke; migraine may be directly associated with an ischaemic stroke (migrainous infarction); migraine may represent a risk factor for stroke; several diseases, mostly genetically determined, include among their clinical manifestations attacks of migraine and stroke; lastly, migraine has been associated with subclinical infarct-like brain lesions and white matter hyperintensities. The risk of cardiac vascular events in migraineurs varies greatly among studies, ranging from a lower-than-average to a moderately increased risk as suggested by the most recent data. Initial evidence also suggested an association between migraine and patent foramen ovale, but this possibility has been recently challenged. The mechanisms underlying the relationship of migraine with cerebrovascular and cardiovascular diseases are still cryptic and rather complex. In migraineurs, a heightened vigilance toward some comorbid risk factor is warranted together with caution in prescribing oral contraceptives.
Migraine and epilepsy
Authors: Parisi Pasquale , Trenité Dorothée Kasteleijn-Nolst , Carpay Johannes A. , Papetti Laura , Paolino Maria Chiara
Published: April 2020

Migraine and epilepsy are both characterized by transient attacks of altered brain function with a clinical, pathophysiological, and therapeutic overlap. Furthermore, epilepsy and migraine may mimic each other. In particular, occipital lobe seizures may be easily misinterpreted as migraine with visual aura, although there seems to be several clinical characteristics that can differentiate between visual auras of epileptic and migrainous origin
Migraine and vertigo
Authors: Cha Yoon-Hee
Published: April 2020

The phenomena of migraine headache and vertigo share many epidemiological, anatomical, and clinical characteristics. The historically parallel development of the neuroscience of each field has formally intersected in the development of consensus criteria for vestibular migraine and the inclusion of vestibular migraine in the International Classification of Headache Disorders. Differences exist in the temporal profile of head pain and vertigo as manifestations of migraine, which can obscure the association. However, the growing body of evidence on the common demographic, neurochemical signature, and treatment responses of pain and vestibular symptoms indicate that they exist as symptoms of a common syndrome, one which can only be fully understood by recognizing the significance of each kind of manifestation.
Treatment and management of migraine
Authors: Charles Andrew , Evers Stefan
Published: April 2020

A significant percentage of individuals with migraine, by some estimates as many as 25%, are candidates for preventive therapy, also known as prophylactic therapy. These are treatments that are administered to pre-empt headache attacks, as opposed to acute treatments that are administered once a headache attack has occurred (although many treatments may be effective both as preventive and acute therapies). There are a variety of options for preventive therapy with widely varying mechanisms of action, and there is no clear-cut single choice for any individual patient. Preventive therapies can be broadly grouped as antihypertensive medications, anticonvulsant medications, antidepressants, vitamins, natural therapies, neurotoxins, and neuromodulation approaches. Early clinical trials indicate that antibody therapies may play an important role as future migraine preventive therapies. While current therapies are effective for some patients, there is a critical need for better means of identifying which strategy is the best for each individual patient, and also for new approaches that are more effective and better tolerated for prevention of migraine overall.
Classification, diagnostic criteria, and epidemiology
Authors: Dirkx Thijs H. , Koehler Peter J.
Published: April 2020

The trigeminal autonomic cephalalgias (TACs), including cluster headache, paroxysmal hemicrania, SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing), SUNA (with cranial autonomic symptoms), and hemicrania continua, belong to the primary headaches. They are characterized by severe unilateral headache attacks in association with ipsilateral cranial autonomic features. Cluster headache is the most frequent of the TACs. The other TACs are rare, but epidemiological data are scarce and variable. The various types of TAC are distinguished not only by differences in attack frequency and duration, but also by differences with respect to treatment response. The typical headache syndromes, fulfilling the International Classification of Headache Disorders-3 criteria, have also been described in association with other disorders and imaging is required to exclude intracranial pathology in all newly diagnosed patients.
Paroxysmal hemicrania
Authors: Bussone Gennaro , Cittadini Elisabetta
Published: April 2020

Paroxysmal hemicrania is classified as a trigeminal autonomic cephalalgia by the International Classification of Headache Disorders, third edition. The current criteria require at least 20 attacks of severe unilateral orbital, supraorbital, or temporal pain, lasting 2–30 minutes, accompanied by ipsilateral cranial autonomic features such as ptosis, eyelid oedema, conjunctival injection, lacrimation, nasal blockage, or rhinorrhoea. Attacks usually have a frequency of more than five per day, and respond exquisitely to indomethacin.
Cluster tic syndrome and other combinations of primary headaches with trigeminal neuralgia
Authors: Wilbrink Leopoldine A. , Haan Joost , Pareja Juan A.
Published: April 2020

Cluster tic syndrome (cluster headache and trigeminal neuralgia) and other combined tic syndromes are very rare and heterogeneously described as case reports in the literature. Three types of cluster tic syndromes can be distinguished: (i) simultaneously occurring trigeminal neuralgia and cluster headache according to the ICHD-2 criteria (most frequent); (2) attacks not fulfilling criteria for either cluster headache or trigeminal neuralgia but having features of both; (iii) secondary cluster tic syndrome. Trigeminal neuralgia can also co-occur with paroxysmal hemicrania (paroxysmal hemicrania tic) and with SUNCT. In case of co-occurrence of two primary headache syndromes, a combination of separate treatments aimed at the two headache syndromes is recommended. The pathophysiology of the tic combination syndromes is unknown.
Tension-type headache
Authors: Evers Stefan
Published: April 2020

Tension-type headache (TTH) is usually a dull, bilateral headache without accompanying symptoms. It is divided into three subtypes: infrequent episodic TTH (< 1 headache day per month), frequent episodic TTH (1–14 headache days per month), and chronic TTH (≥ 15 headache days per month). This division is highly relevant for three reasons. Firstly, impact on quality of life differs considerably between the three subtypes. Secondly, the pathophysiological mechanisms also differ. Peripheral mechanisms such as muscle tension are more important in episodic TTH, whereas central pain sensitization with reduced antinociceptive mechanisms are pivotal in chronic TTH. Thirdly, treatment differs between the subtypes, with symptomatic and prophylactic treatment being more appropriate for episodic and chronic TTH, respectively. Non-pharmacological management should always be part of the treatment. Patients with episodic TTH are treated with analgesics, while prophylactic drugs (in particular antidepressants) should be considered in patients with very frequent episodic or chronic TTH.
Chronic migraine and medication overuse headache
Authors: Dodick David W. , Silberstein Stephen D.
Published: April 2020

Thunderclap headache refers to the abrupt onset of a severe headache. Characteristics of the pain are not strictly defined, but intensity is considered to peak in seconds to a minute. This chapter focuses on the work-up of alert neurologically intact patients presenting with an acute and severe headache, not related to trauma. Work-up to detect or exclude a subarachnoid haemorrhage is described first, followed by an overview of investigations to detect a cerebral aneurysm. Thereafter, other secondary causes of thunderclap headache and their suitable analysis will be discussed, followed by a brief overview of primary thunderclap headaches.
Headache attributed to spontaneous intracranial hypotension
Authors: Amoozegar Farnaz , Dilli Esma , Halker Rashmi B. , Starling Amaal J.
Published: April 2020

Spontaneous intracranial hypotension (SIH) caused by a spontaneous cerebrospinal fluid (CSF) leak, results in CSF hypovolaemia. Owing to the variety of clinical presentations and numerous possible diagnostic investigations, diagnosis and appropriate treatment remains challenging in many patients. Although the typical presentation of SIH is an orthostatic headache, the clinical spectrum includes a variety of headache types, focal neurological symptoms, and even spinal manifestations. The underlying pathophysiology of SIH varies depending on the clinical scenario. However, a deeper understanding of the pathophysiology has led to the recognition of risk factors and an explanation for clinical symptoms and abnormalities on diagnostic investigations. Multiple diagnostic investigations can be used to determine if a CSF leak is present or not. Magnetic resonance imaging of the head with and without contrast is sensitive and non-invasive. However, computed tomography myelography remains the study of choice to locate the site of the leak. The rate of flow of the CSF leak can pose a challenge to standard diagnostic investigations. To date, a large-volume blind epidural blood patch is the mainstay of treatment, although more targeted approaches are used for more refractory cases.
Remote causes of ocular pain
Authors: Friedman Deborah I.
Published: April 2020

Ocular and periocular pain may occur with processes occurring remotely from the eye, including primary headache disorders, pain originating in branches of the trigeminal nerve, and, occasionally, disorders of the upper cervical spine. The primary headaches producing periocular pain include migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias, paroxysmal hemicrania, and other miscellaneous headaches not associated with a structural lesion. This chapter focuses on unusual primary headache disorders that manifest as eye pain, as well as secondary causes of ocular pain, including ophthalmic and orbital conditions, inflammatory and infectious processes, cranial neuralgias, and vascular disorders
Nasal and sinus headaches
Authors: Martin Vincent T. , Vincent Maurice
Published: April 2020

Very few topics in the headache field engender more controversy than sinus headache. Patients often believe that their headaches are attributed to sinus disorders because they experience rhinitis symptoms (e.g. rhinorrhoea, nasal congestion, and postnasal drip) during their attacks. Primary care physicians, otolaryngologists, and allergists often diagnose sinus headaches and treat them with rhinitis medications, antibiotics, allergy shots, and surgical interventions, with varying levels of success. In contrast, most neurologists and headache specialists believe that many patients with a diagnosis of sinus headache are suffering from migraine, or another primary headache disorder.
Headaches in the young
Authors: Guidetti Vincenzo , Bellini Benedetti , Hershey Andrew D.
Published: April 2020

This chapter will review the those aspects that are specifically related to migraine in children and adolescents. Recurrent headaches are a common health complaint for children and adolescents. When these headaches recur and are brought to medical attention, they are more frequently noted to be migraine, but there are also a significant number of patients with tension-type headache. The pathophysiology, characteristics, and response to treatment for children and adolescents can be considered to be similar to adults, with unique aspects that correlate to the developmental level of the children and the progression of their disease.
Headache and the weather
Authors: Schoonman Guus G. , Hoffmann Jan , Becker Werner J.
Published: April 2020

There is a widespread belief that weather and other atmospheric factors can have a negative effect on health, in general, and headache, in particular. When studying the association between weather-related variables and headache a few questions arise: (i) What is weather? (ii) Do patients think weather is a trigger factor for headache? (iii) Are there any objective prospective studies and is it possible to quantify a possible association between variables and headache? (iv) What are the difficulties in studying the relation between weather and headache? Firstly, what is weather? Is it just the variables that are presented in your daily weather report? In general, meteorological data consist of temperature, wind, barometric pressure, and humidity. For this chapter, it was decided to include both classic weather-related variables, as well as other atmospheric factors, such as air pollution, altitude, diving, and electromagnetism.
Measurement in mental health
Authors: Prince Martin , Chua Kia-Chong
Published: April 2020

Measurement is fundamental to quantitative research in general, and there are particular issues with respect to the domain of mental health. Students will need to engage with this issue in practice, as they develop measurement strategies and select individual measures for their own research, and as an important component of their assessment of the quality of published research. In this chapter, we consider the levels and types of measure; the domains of measurement (what is it you want to measure); how to go about selecting a measure for a particular purpose; and how to develop a scale-based measure should there be a need to do so. We examine in more detail what is meant by the psychometric properties of measures, fundamentally their validity and reliability, and how these properties are assessed and quantified.
Qualitative research
Authors: Mitrofan Oana , McCabe Rose
Published: April 2020

This chapter offers an overview of the nature and purpose of qualitative research, its methods and processes, quality appraisal, synthesis of qualitative research, and the integration of qualitative and quantitative approaches in mixed methods research. It includes a brief description of the approaches commonly used in health and healthcare research to collect and analyse qualitative data. The authors make suggestions and provide examples to illustrate the decision-making process in choosing the method(s) of data collection when designing a qualitative project. A number of ways to ensure scientific rigour in the design, conduct, and reporting of qualitative research, with particular regard to validity and reliability, are summarized. The last two sections focus on the key strengths and limitations of qualitative research. A few practical exercises are provided at the end of this chapter to assist the reader in revising the basic steps in the design of a qualitative research project.
Surveillance, case registers, and big data
Authors: Ford Tamsin , Stewart Robert , Downs Johnny
Published: April 2020

Health and social care organizations routinely collect huge amounts of data, which are a potentially useful resource for researchers who wish to study clinical issues ‘in vivo’. This chapter describes the types of research that typically use these data in mental healthcare, with a focus on surveillance, case register, and ‘big data’ approaches. To start, the chapter illustrates the importance of surveillance in the study of mental health, with a focus on using clinical surveillance to study patterns of rare psychiatric disorders and events. It then summarizes the contributions of psychiatric case registers to descriptive, analytical, and trial study designs. Finally, it reviews how digitized health and social information are being linked and analysed using big data techniques. Throughout, the chapter outlines the strengths and weaknesses of these epidemiological approaches, and provides practical guidance on how researchers may address the methodological and governance challenges that these clinical data sources present.
Gene–environment interaction
Authors: Morgan Craig , Forti Marta Di , Fisher Helen L.
Published: April 2020

For all major mental disorders there are many factors that, in combination and through multiple pathways, increase or decrease the risk of onset. These include, to varying degrees, genetic and environmental factors. This chapter provides an introduction, from an epidemiological perspective, to the study of gene–environment interaction. It begins by providing a working definition of gene–environment interaction, rooted in a sufficient causes framework, and then considers, in turn, the prominent puzzles and challenges, including the statistical modelling of interaction, the main study designs (including strengths and weaknesses), measurement of environmental exposures, and required sample sizes. The chapter concludes with a consideration of the implications of recent advances in genetics for studies of gene–environment interaction.
Health economics for psychiatric epidemiology
Authors: Heslin Margaret , McCrone Paul , Chisholm Daniel
Published: April 2020

This chapter examines the interface between psychiatric epidemiology and health economics, particularly in relation to mental health service planning and evaluation. It describes examples of how economics and epidemiology work together to produce innovative research approaches from basics such as burden of disease and cost-of-illness studies to more complex approaches such as the assessment of mental health system financing and economic evaluation of mental healthcare interventions. It rounds up with a summary of how to conduct economic evaluations, including sections on study design, mode of economic evaluation, and costing perspective.
Life course epidemiology
Authors: Richards Marcus , Hardy Rebecca
Published: April 2020

Types of psychiatric disorders vary with respect to age of onset, temporal continuity, and impact. Life course epidemiology provides powerful tools for understanding these complexities. This discipline broadly distinguishes ‘sensitive period’ and ‘risk accumulation’ models. The former refers to optimum windows for exposure (e.g. early life for some psychoses, in contrast to proximal exposures for depression). Accumulation refers to additive or multiplicative effects of multiple exposures, exemplified by stress process and chain of risk models. The preeminent study design for these approaches is the prospective longitudinal birth cohort study, especially where multiple cohorts help to distinguish period and cohort effects. However, limitations such as balancing the need for repeated versus age-appropriate measurement, and non-random missing data, must be carefully considered. While the statistical workhorse for life course epidemiology is general linear modelling, this discipline also requires advanced tools such as random effects, path, latent class, and latent growth modelling.
Psychiatric epidemiology: Looking to the future
Authors: Das-Munshi Jayati , Ford Tamsin , Hotopf Matthew , Prince Martin , Stewart Robert
Published: April 2020

In this final chapter to the second edition of Practical Psychiatric Epidemiology, developments in psychiatric epidemiology since the first edition are summarized and the editors offer a view on where the future may lie. The themes summarized in this chapter include those related to large-scale datasets or ‘big data’, new technologies and science communication (including data generated through GPS tracking systems and the impact of social media), expanding biological data and biobanks, as well as the impact of globalization, migration, and culture on understanding psychiatric epidemiological principles. The last part of this chapter raises the important issue of open science initiatives. The chapter concludes with a brief discussion on the constancy and ongoing evolution of psychiatric epidemiology.
Cardiology
Authors: Frise Charlotte , Collins Sally
Published: April 2020

Pregnancy is associated with global haemodynamic changes, which occur early and gradually return to normal after delivery. This chapter covers the changes in physiological cardiac changes, before covering over 40 different cardiac conditions and syndromes, including inherited defects, problems arising from prosthetic heart valves, aortic pathologies, cardiomyopathies, as well as cardiac problems specific to the pregnant patient.
Renal disease
Authors: Frise Charlotte , Collins Sally
Published: April 2020

This chapter begins by describing the normal physiological changes that occur in pregnancy, including changes in tubular function, increased renal size, and increased blood flow. It then describes management strategies in a range of renal disorders, including haematuria, proteinuria, urinary tract infections, and both acute and chronic kidney disease. Hyperkalaemia, dialysis (and haemodialysis in pregnancy), transplantation, and medications suitable for use in the pregnant patient are all described, among others.
Endocrinology
Authors: Frise Charlotte , Collins Sally
Published: April 2020

This chapter covers endocrinology in the pregnant patient. Hormone changes are tabulated, common pituitary tumours, thyroid antibodies, thyroiditis (fetal, neonatal, and postpartum) alongside investigations, clinical symptoms, acidosis and alkalosis, and effects of obesity of pregnancy are all described. Management strategies are included, as well as risk factors for both the mother and fetus.
Oncology
Authors: Frise Charlotte , Collins Sally
Published: April 2020

Principles of managing cancer during pregnancy are described in this chapter. Subsequently, the background, clinical features, and management of breast and cervical cancer, melanoma, Hodgkin’s lymphoma, and acute leukaemia are separately covered. Preserving fertility, late effects on treatment, and neutropenic sepsis are also described.
Perinatal mental health
Authors: Frise Charlotte , Collins Sally
Published: April 2020

This chapter covers perinatal mental health problems, both those that develop in pregnancy and those that may be encountered as pre-existing when a patient becomes pregnant. Specific phobias relating to the state of being pregnant (tocophobia) or issues encountered in pregnancy (blood, injury, and injection phobia), as well as depression, schizophrenia, eating disorders, self-harm, and substance abuse are covered. Treatment without consent and the role of the mother and baby unit are discussed.
Assessment of the urinary tract
Authors: Jefferis Helen , Price Natalia
Published: April 2020

This chapter covers assessment techniques for examining the urinary tract. It begins with symptoms and definitions that indicate assessment would be necessary and a procedure for general initial assessment, and baseline investigations. It then explains cystoscopy and relevant findings, urodynamic tests, uroflowmetry, cystometry, and filling cystometry, as well as additional urodynamic tests (e.g. ambulatory urodynamics and videourodynamics). Finally, urethral pressure profilometry for testing urethral function are described. Guidelines to the correct terminology used to describe symptoms and diagnoses are laid out as well as definitions of compliance and contractility, along with illustrative figures to show the assessment process of the urinary tract.
Lower urinary tract conditions
Authors: Jefferis Helen , Price Natalia
Published: April 2020

This chapter covers conditions affecting the lower urinary tract. It begins with an overview and management strategies of overactive bladder syndrome, including both conservative and pharmacological methods. Stress urinary incontinence (SUI) is covered in detail, from an overview and risk factors, to conservative, surgical, and other interventions. The controversy surrounding synthetic mid-urethral slings is highlighted. Other types of urinary continence are defined, alongside voiding dysfunction. Finally, drugs that can affect bladder function are listed.
Colorectal
Authors: Jefferis Helen , Price Natalia
Published: April 2020

This chapter covers colorectal problems. It starts with different investigations for physiology, musculature, and transit, then goes on to discuss the causes, assessment, and management of constipation. Different types of laxatives are described. Specific conditions, including obstructed defaecation syndrome, rectal prolapse, and intussusception are covered. Causes, management, and surgical interventions of faecal incontinence are described. Finally, the causes and management of rectovaginal fistula are defined.
Pregnancy and childbirth
Authors: Jefferis Helen , Price Natalia
Published: April 2020

This chapter covers the normal physiological changes to the renal tract, bladder, and pelvic floor that is associated with pregnancy. It then explains perineal trauma and its classification, and obstetric anal sphincter injury. The types, risk factors, and management of postpartum urinary retention is also covered.
Miscellaneous
Authors: Jefferis Helen , Price Natalia
Published: April 2020

This chapter covers the definition of a urogynaecologist and current training routines, including the specialty, advanced training skills modules (ATSMs), and specific subspecialty training. The composition and role of both local and regional multidisciplinary team (MDT) is described. Finally, the current controversies around the use of synthetic mesh, and the current UK suspension of all vaginal mesh use for both prolapse and incontinence, is covered.
Definitions and measurement of negative symptoms in schizophrenia
Authors: Bitter István
Published: April 2020

Negative symptoms of schizophrenia represent deficits in different domains, e.g. loss or diminution in emotions, thinking and movement. Persistent primary negative symptoms are considered to be part of the schizophrenia disease process and represent an unmet need for treatment, while secondary negative symptoms are associated with positive symptoms of schizophrenia, other mental disorders (e.g. depression, substance abuse), extrapyramidal symptoms, social deprivation, etc. Validated rating scales are helpful in the evaluation and measurement of negative symptoms. Current consensus supports the focus on the following five domains (five ‘As’): blunted affect, alogia, anhedonia, asociality, and avolition.
Long-term course of negative symptoms in schizophrenia
Authors: Smulevich Anatoly , Romanov Dmitry
Published: April 2020

The chapter focuses on the relationship of negative and positive symptoms in schizophrenia. Negative symptoms should be evaluated in a relation to positive symptoms both cross-sectionally and long term (prospectively/retrospectively). Two types of long-term interaction between negative and positive symptoms could be distinguished: (1) relatively synchronized, and (2) relatively desynchronized. Synchronization of negative and positive symptoms is characterized by their unidirectional long-term course. Desynchronization is characterized by their bidirectional long-term relations: (1) negative schizophrenia with minimal positive symptoms at the beginning of the disease and further progression of negative symptoms; or (2) schizophrenia with negative symptoms ‘that stopped at the very beginning’, and the later course is characterized by positive symptoms. Considering every single time point of the long-term relationship between negative and positive symptoms (cross-sectionally), the chapter describes the concept of ‘mutual/common syndromes’ (consisting of both positive and negative symptoms) at different stages of schizophrenia, including residual deficit states.
Case 1
Authors: Humphreys Hilary
Published: April 2020

Cellulitis is infection of the dermis and subcutaneous tissues unlike erysipelas which is more superficial and necrotizing fasciitis which involves deeper layers. Cellulitis is most commonly caused by Group A streptococci (GAS) and Staphylococcus aureus, including Panton–Valentine leukocidin-producing isolates. However, most cases are diagnosed clinically and the initial drug of choice is flucloxacillin. Five to ten days of treatment is usually adequate including an early intravenous to oral switch but prophylactic antibiotics may be considered for patients with two or more episodes to prevent further recurrence. There is poor evidence for the benefit of using adjuvant therapy, such as corticosteroids and intravenous immunoglobulin, in more severe cases. Healthcare-associated clusters or outbreaks may be associated with carriage of GAS in a staff member who should be treated if positive.
Case 2
Authors: Ramasamy Maheshi
Published: April 2020

Toxic shock syndrome (TSS) is a rare but serious clinical syndrome characterized by shock and multi-organ failure. The condition is mediated by toxins produced by Staphylococcus aureus or Streptococcus pyogenes bacteria which act as immunological superantigens. Superantigens non-specifically cross-link MHC molecules on antigen presenting cells with T cell receptors, driving polyclonal T cell expansion. The resultant inflammatory cytokine storm increases capillary permeability, resulting in organ dysfunction. Diagnosis is based on clinical criteria such as hypotension, rash, desquamation, and fever. The treatment of TSS usually requires admission to a high dependency unit for management of septic shock and its complications, antibiotic therapy, and source control.
Case 5
Authors: Humphreys Hilary
Published: April 2020

Erythema migrans is the most common skin manifestation of Lyme disease caused by Borrelia spp. There are some differences in the clinical presentation and aetiology between cases in Europe and the United States as the vectors and Borrelia spp. vary. The diagnosis is usually confirmed by serology, that is, enzyme immune-assay and Western blot, although there are other approaches such as PCR. Apart from erythema migrans, other manifestations include meningitis, heart block, and arthritis. There are a number of options for treatment, including tetracyclines and penicillins, and duration depends on the presence of complications. There is a limited if any role for prophylactic antibiotics to prevent acquisition after exposure to a tick. Much controversy surrounds chronic Lyme disease which may not be a real clinical entity and may mimic other conditions such as connective tissue diseases. There is no evidence that ongoing symptoms are due to persistent infection.
Case 9
Authors: Jones Nicola
Published: April 2020

Severe respiratory infections in returning travellers usually present to Emergency Departments and then require intensive care support. There needs to be early and rapid assessment, including a detailed travel and exposure history to assess the risk of highly pathogenic imported respiratory viruses with potential for transmission to healthcare workers. Such cases need to be managed with appropriate infection control precautions, rapid diagnostics, supportive therapy, and, in most cases, antivirals. A case returning from the Middle East is described
Case 10
Authors: Woodhouse Andrew
Published: April 2020

Multi-drug resistant tuberculosis (MDR-TB) is defined by resistance to both isoniazid and rifampicin, the two most effective first line anti-tuberculous drugs. Resistance to one or other drug plus resistance to other first line agents (streptomycin, pyrazinamide and ethambutol) represents an important treatment challenge. The case provides insight into the challenges faced treating MDR-TB and extensively drug-resistant tuberculosis (XDR-TB).
Case 11
Authors: Woodhouse Andrew
Published: April 2020

Whooping cough is a highly contagious respiratory illness caused by the bacterium Bordatella pertussis. Neonates and infants under 2 months of age are at most risk of severe disease and even death. The vast burden of disease is in resource-poor areas of the world due to the beneficial impact of effective vaccination programmes in wealthy regions. Nonetheless outbreaks continue to occur and sporadic cases in older people can be an important source of infection for susceptible groups
Case 12
Authors: Atkins Bridget
Published: April 2020

Lung infiltrates in immunocompromised patients have a broad differential diagnosis. Assessment should include considering host risk factors, the clinical presentation, and imaging. Cross-sectional imaging is very helpful and lower respiratory tract samples should be obtained where possible. Laboratory diagnostic tests should be performed but most have low sensitivity and specificity. The differential diagnosis includes non-infective and infective cause. Effective patient management requires good supportive therapy if in respiratory failure, prompt diagnostics, early empiric antimicrobial treatment, and management of the underlying immunosuppression.
Case 16
Authors: Woodhouse Andrew
Published: April 2020

Liver abscess is often seen as a complication of biliary tract disease or intra-abdominal pathology with infection spreading to the liver via the portal venous system. Abscess can also arise from systemic bacteremia or bloodstream infection via the hepatic vein or by direct extension from an adjacent focus. Imaging with ultrasound and/or CT scan can confirm abscess and allow radiologically guided sampling, to help guide antimicrobial therapy, and therapeutic drainage. The majority of abscesses are pyogenic but amoebic and mycobacterial causes may need to be considered in certain situations.
Case 17
Authors: Humphreys Hilary
Published: April 2020

Clostridioides difficile infection (CDI) is a significant adverse event of healthcare and usually follows recent antibiotics. It is increasingly seen outside the acute hospital setting such as in nursing homes and the laboratory diagnosis is evolving. Demonstration of toxin in the stool such as through an immuno-assay (IA) test preceded by a screening test, such as the glutamate dehydrogenase test or polymerase chain reaction (PCR) to detect the toxin gene, is commonly adopted. It is important to recognize severe CDI early as this may require surgical intervention and recurrent CDI—a return of symptoms with laboratory confirmation within 8 weeks of the original episode—occurs in 15–20% of patients. In addition to stopping all precipitating antibiotics and the use of vancomycin, recent years have seen the emergence of new therapeutic approaches such as fidaxomicin, monoclonal antibodies, and faecal microbiota transplantation (FMT).
Case 18
Authors: Woodhouse Andrew
Published: April 2020

Traveller’s diarrhoea is among the commonest health problems to afflict travellers to resource-poor countries. It is most commonly caused by E. coli, either enterotoxigenic or enteroaggregative, although there is geographic variation. Most cases are self-limiting but can be debilitating and maintaining hydration is important. Antibiotics are sometimes recommended for travellers to carry as standby treatment, particularly if they are going to be in remote areas or are immunocompromised. Prophylaxis is not recommended for the majority of situations.
Case 21
Authors: Irving Will
Published: April 2020

Chronic hepatitis C (HCV) infection may be completely asymptomatic until the patient presents with complications of end-stage liver disease. Hence, anti-HCV testing should be performed on any patient with risk factors, which includes a raised alanine aminotransferase. Following diagnosis of chronic HCV infection, it is essential to know the genotype of the infecting virus, and whether or not the patient has underlying cirrhosis, as both of these factors will be important in determining the optimal therapeutic regimen. Direct-acting antiviral agents target 3 different viral non-structural proteins. The success of these drugs in achieving sustained virologic response (SVR) in well over 90% of patients in clinical trials has ended the era of interferon-based therapy for this infection. Therapy for most patients comprises one co/multiply-formulated tablet taken orally per day for 8 or 12 weeks.
Case 24
Authors: Wong T H Nicholas
Published: April 2020

BK virus are human polyomaviruses associated with BK virus-associated nephropathy (BKVAN) in post-transplant recipients on immunosuppression. Primary infection is usually asymptomatic, and the virus will remain in a latent phase. Reactivation usually occurs due to a number of risk factors, namely target organ damage and a reduction in the host immune function. BK virus can also cause haemorrhagic cystitis in haemopoietic stem cell transplant recipients. Diagnosis of BKVAN can range from visualization of decoy cells in urine microscopy (low sensitivity and high specificity) to serum and urine polymerase chain reaction (PCR) (high sensitivity and high specificity). Screening for BKVAN is generally recommended post transplantation. There is currently no specific antiviral therapy and the mainstay of treatment involves reduction in immunosuppressive agents.
Case 29
Authors: Barrett Lucinda , Atkins Bridget
Published: April 2020

Neurosurgical infections include those of devices such as external ventricular drains and permanent shunts (e.g. ventriculo-peritoneal and ventriculo-atrial). Organisms can form biofilm on the surface of such devices, sometimes sufficient to cause blockage. Patients may present with signs of meningitis or of shunt blockage. In the intensive care setting patients may have fever and/or deterioration in their neurological status. These infections are complex to manage as they usually require removal/revision of the device and delivery of high levels of antibiotics to the central nervous system. Each of these has risks and needs to be expertly managed. This case describes an acute infection in an external ventricular drain.
Case 34
Authors: Humphreys Hilary
Published: April 2020

Multi-drug-resistant Enterobacteriales are an increasing problem and include those mediated by extended-spectrum β‎-lactamases (ESBLs) and carpapenemase production (CPE). Third-generation cephalosporins are inactivated by ESBLs but for CPEs there are much fewer options for treatment. The challenge in detection, management, and treatment is compounded by CPEs occurring amongst such a broad category of Gram-negative bacilli and because the genetic elements are very mobile, often being quickly and widely disseminated through plasmids. Phenotypic tests for identification have their limitations and there is increasing emphasis on PCR with microarrays and whole genome sequencing being available in specialist centres. Colistin is often the drug of first choice for CPE infections but is usually combined with another agent such as an aminoglycoside. Aggressive infection prevention and control precautions are mandatory given the propensity to spread, the reduced options for treatment, and a lack of insight to patterns and duration of carriage.
Case 37
Authors: Woodhouse Andrew
Published: April 2020

Leishmaniasis is an intracellular protozoan parasitic infection caused by organisms of the genus Leishmania. The parasite is usually transmitted to humans by the bite of Phlebotomine sandflies. A spectrum of illness is seen ranging from localized skin ulceration (which can be self-limiting) to disseminated systemic infection which can be fatal. Different species of Leishmania cause different forms of disease and the species are restricted in their geographic distribution. Host factors also seem to be important in determining how the infection will manifest itself.
Case 38
Authors: Woodhouse Andrew
Published: April 2020

Post-transplant lymphoproliferative disease (PTLD) is a disorder of lymphoid proliferation seen in recipients of solid organ or haematopoietic transplants as a consequence of immunosuppression. A spectrum of disease is recognized ranging from non-malignant polyclonal proliferation of B cells to monoclonal proliferation of B or T lymphocytes which have features in common with lymphomas. Epstein–Barr virus (EBV) is associated with a majority of cases although it is not a universal feature. Treatment with anti-CD20 antibody in addition to reduction in immunosuppression has become the most common treatment approach.
Case 45
Authors: Woodhouse Andrew
Published: April 2020

The term viral haemorrhagic fever (VHF) describes a syndrome caused by a diverse group of viral infections. The recent Ebola virus disease (EVD) outbreak in West Arica has heightened awareness of viral haemorrhagic fevers in non-endemic countries. A robust and consistent approach to the early recognition of possible VHF is crucial to appropriate management. The EVD epidemic has led to renewed interest and effort in treatment and vaccine development directed at Ebola virus and other causes of VHF.
Case 47
Authors: Humphreys Hilary
Published: April 2020

Mucormycosis can mimic aspergillosis, both clinically and radiologically. High-risk patient groups include those with acute myeloid leukaemia, following stem cell transplantation, solid organ transplantation, and poorly controlled diabetes mellitus, such as diabetic ketoacidosis against a background of poor social conditions. Persistent symptoms of sinusitis in an at-risk patient, should suggest rhinocerebral mucormycosis. Direct tissue microscopy with specialized stains (e.g. Grocot) is the mainstay of diagnosis but pan-fungal PCR assays are being evaluated. Aggressive debridement, which sometimes needs to be repeated, together with antifungal agents such as amphotericin B and/or, increasingly, posaconazole often for months, are required in the management of this challenging infection. However, the outcome is often dependant on the underlying condition, degree of immunosuppression, and whether it can be reduced.
InterPred: a webtool to predict chemical autofluorescence and luminescence interference
Authors: Borrel Alexandre , Mansouri Kamel , Nolte Sue , Saddler Trey , Conway Mike , Schmitt Charles , Kleinstreuer Nicole C
Published: April 2020

High-throughput screening (HTS) research programs for drug development or chemical hazard assessment are designed to screen thousands of molecules across hundreds of biological targets or pathways. Most HTS platforms use fluorescence and luminescence technologies, representing more than 70% of the assays in the US Tox21 research consortium. These technologies are subject to interferent signals largely explained by chemicals interacting with light spectrum. This phenomenon results in up to 5–10% of false positive results, depending on the chemical library used. Here, we present the InterPred webserver (version 1.0), a platform to predict such interference chemicals based on the first large-scale chemical screening effort to directly characterize chemical-assay interference, using assays in the Tox21 portfolio specifically designed to measure autofluorescence and luciferase inhibition. InterPred combines 17 quantitative structure activity relationship (QSAR) models built using optimized machine learning techniques and allows users to predict the probability that a new chemical will interfere with different combinations of cellular and technology conditions. InterPred models have been applied to the entire Distributed Structure-Searchable Toxicity (DSSTox) Database (∼800,000 chemicals). The InterPred webserver is available at https://sandbox.ntp.niehs.nih.gov/interferences/.