bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognizing the Psychiatric Burden of Anxiety and Depression in Children With Headache, Chest Pain, and Abdominal Pain
Authors: Tran Susan T. , Goya Arce Ana B. , Jagpal Anjana
Published: September 2020

Anxiety and depression are particularly common in pediatric chest, abdominal, and headache pain. Shared genetic factors, biological processes, and neurochemical mechanisms may underlie these comorbidities. Chronic pain in children and adolescents is associated with substantial functional disability, and impairments are especially notable when youths have comorbid anxiety or depression. Thus, early detection and treatment of comorbid psychiatric conditions in youths with chronic pain is imperative. Screening for anxiety and depression in pediatric pain is made difficult by the number of overlapping symptoms between pain and psychiatric conditions. Research on the treatment of chronic pain and comorbid depression or anxiety has advanced, but larger trials with follow-up data are needed to improve confidence in effectiveness. Implications for considering developmental and familial factors in the screening and treatment of depression and anxiety in youths with chronic pain are discussed.
Cultural Spectrum of Chronic Pain and Somatization Syndromes
Authors: Desai Geetha , Chaturvedi Santosh K. , Bhugra Dinesh
Published: September 2020

Chronic pain and somatization are common reasons for consultation in health settings, including psychiatric services, in India. These are often manifestations of underlying psychiatric illnesses such as depression, anxiety, and other stress-related disorders. Assessment of chronic pain and somatization is essential because it may be a means for the patient to communicate psychological distress, arising out of stress and conflicts within the environment. Sociocultural factors have an important role in the manifestations, help-seeking, and management of these chronic pain and somatizing syndromes. Some specific pain syndromes and somatizing syndromes are seen in India, including that syndrome, sinking heart syndrome, and a variety of somatic neuroses. The management of pain and somatizing syndromes requires a multidisciplinary approach, with an aim to reduce distress and enhance quality of life, in an ethical way.
Jaki, a Puzzling Inca Syndrome of Comorbid Pain and Mental Illness
Authors: Incayawar Mario
Published: September 2020

The clinical encounter with a patient who is suffering from chronic pain and a psychiatric disorder is challenging. This can become a clinical conundrum if the patient has a different cultural background than the physician and says he or she has a mysterious culture-bound syndrome. This chapter discusses a Quichua-Inca illness experience called Jaki, a frequent condition that is well-known by millions of Quichua patients in the Andes, South America. Biomedically trained doctors usually dismiss it as a condition without any medical importance experienced by superstitious and primitive people. In contrast, Jaki patients believe it is a complex and threatening illness that could lead to death. They recognize four types of Jaki and believe the causes are related to “evil spirits” and that proper treatment should address them. The author conducted a transcultural psychiatry study showing that most Jaki patients are suffering from depression, anxiety, somatoform disorders, psychological factors affecting a physical condition, and adjustment disorders. Jaki patients are suffering indeed from comorbid chronic pain and psychiatric disorders. The chapter concludes with clinical recommendations for the practitioner who is willing to avoid racial bias, improve cultural competency, and offer culturally sensitive and better quality medical care.
Epidemiology of Substance Use Disorders
Authors: Morgan Snell L. , Barnes Andrew J. , Cunningham Peter
Published: September 2020

Nearly 3 million Americans have a current or previous opioid use disorder, and recent data indicate that 10.2% of US adults have ever misused pain relievers. In 2015, approximately 800,000 individuals used heroin, while 4 million misused prescription opioids. Although use of other drugs such as alcohol and cannabis is more prevalent, opioid use contributes to significant morbidity, mortality, and social and economic costs. While the current US opioid overdose epidemic began with prescription opioids, since 2015, heroin and synthetic opioids (e.g., fentanyl) have driven continued increases in opioid overdose deaths, contributing to a recent decline in overall life expectancy in the United States. Policies to address the opioid epidemic by changing clinical practice include provider education, monitoring prescribing practices, and expanding the clinical workforce necessary to treat opioid use disorders. The opioid epidemic appears to be largely a US phenomenon and a consequence of both structural challenges in the US healthcare system and growing socioeconomic disparities, and thus it will require policies including and beyond delivery system reforms to resolve it.
Exploiting Hope
Authors: Snyder Jeremy
Published: September 2020

One often hears stories of people in terrible and seemingly intractable situations who are preyed upon by individuals offering empty promises of help. Frequently these cases are condemned as “exploiting the hope” of another. These accusations are made in a range of contexts, including human smuggling, the beauty industry, and unproven medical interventions. This concept is meant to do heavy lifting in public discourse, identifying a specific form of unethical conduct. However, it is poorly understood what is meant to be wrong by the accusation of exploiting hope, the range of activities that can accurately be captured under this concept, and what should be done about it. Thus, it is an ethical concept that is ripe for extended analysis and discussion. This book offers a close study of the concept of exploiting hope. First, it examines this concept in the abstract, including a close look at how this term is used in the popular press and individual examinations of the concepts of exploitation and hope. This theory-based section culminates in the author’s own account of what it is to exploit hope and when and why doing so is morally problematic. The second section of the book examines how hope for improved health from unproven medical interventions can be exploited. This includes exploitation of hope in the context of participants in clinical trials, purchasing unproven stem cell interventions, right to try legislation, and crowdfunding for unproven interventions.
What Is Exploitation?
Authors: Snyder Jeremy
Published: September 2020

Chapter 2 reviews academic accounts of exploitation. The dominant understanding of exploitation links it to a form of unfairness. Wertheimer argues that a transaction can have features that make it “specially” unfair, as when an employer has a monopoly on employment opportunities. Alternatively, an exchange can be unfair considering a structural injustice that systematically advantages the exploiter. In these cases, employers may have a political responsibility to address structural injustice to avoid exploitation. Contemporary accounts of exploitation also link it to a failure of respect for others. This failure of a duty of respect is linked to a specified duty of beneficence, where our entanglements with others serve to specify specific obligations to aid others in developing and maintaining their distinctive human capacities. The author argues that each of these accounts of exploitation picks out a different kind of moral wrong and is useful for understanding exploitation in different contexts.
Exploiting Hope
Authors: Snyder Jeremy
Published: September 2020

In the Chapter 4 the author argues that fairness-based accounts of exploitation form a poor basis for understanding the distinctive wrongness of exploiting hope. Structural fairness or justice-based accounts are also problematic in the medical context. Structural exploitation can describe some instances of injustices giving rise to the potential for exploitation but not the distinctive character of exploiting hope. Rather, exploitation understood as a failure of respect gives the best interpretation of what is distinctly wrong with exploiting hope. Specifically, individuals with weighty hopes who take risky leaps of hope partially entrust their welfare to others. This entrustment creates obligations for others who may exploit an individual’s hopes when they use this relationship as an opportunity for gain without duly discharging their responsibilities for the hopeful person’s welfare. This is true of both genuine hope and false hope, where the hope is based on misinformation, misunderstanding, and/or fraud.
Selling Hope
Authors: Snyder Jeremy
Published: September 2020

Some individuals seek to sell unproven interventions directly to consumers ahead of evidence. Chapter 6 examines the case of direct to consumer sales of unproven stem cell products to seriously ill individuals. In many cases, clinics selling these interventions are owned by or employ physicians both to administer these treatments and bolster these business’ credibility. Physicians have been willing to misrepresent the evidence supporting such interventions and abuse the trust of their patients in order to pursue these business opportunities. In doing so, they can act against their patients’ welfare, prioritize their own private interests over the health of their patients, and thus exploit their patients’ hope.
Psychiatry’s inchoate wish for a paradigm shift and the biopsychosocial model of mental illness
Authors: Thornton Tim
Published: September 2020

‘Psychiatry’s inchoate wish for a paradigm shift and the biopsychosocial model of mental illness’ critically examines the much discussed goal of a paradigm shift in psychiatric taxonomy. The chapter first highlights some illustrative calls for such a change and then sets these against the Kuhnian account of science from which the idea is taken, highlighting the connection to incommensurability. Relative to a distinction drawn from Winch, between putative sciences where the self-understanding of subjects plays no role and those where it is fundamental, psychiatry falls into the latter kind. This suggests that the wish for a paradigm shift in psychiatry is either incoherent or a wish for a radical but unpredictable overhaul of a significant aspect of our self-understanding as subjects and agents. The biopsychosocial model of mental illness is thus a helpful reminder of the cost of a paradigm shift in psychiatry.
Mental illness: The collision of meaning with mechanism
Authors: Hyman Steven E. , McConnell Doug
Published: September 2020

‘Mental illness: the collision of meaning with mechanism’ is based on the views of psychiatry that Steven Hyman articulated in his Loebel Lectures—mental illness results from the disordered functioning of the human brain and effective treatment repairs or mitigates those malfunctions. This view is not intended as reductionist as causes of mental illness and contributions to their repair may come from any source that affects the structure and function of the brain. These might include social interactions and other sources of lived experience, ideas (such as those learned in cognitive therapy), gene sequences and gene regulation, metabolic factors, drugs, electrodes, and so on. This, however, is not the whole story for psychiatry on Hyman’s view; interpersonal interactions between clinicians and patients, intuitively understood in such folk psychological terms as selfhood, intention, and agency are also critical for successful practice. As human beings who are suffering, patients seek to make sense of their lives and benefit from the empathy, respect, and a sense of being understood not only as the objects of a clinical encounter, but also as subjects. Hyman’s argument, however, is that the mechanisms by which human brains function and malfunction to produce the symptoms and impairments of mental illness are opaque to introspection and that the mechanistic understandings necessary for diagnosis and treatment are incommensurate with intuitive (folk psychological) human self-understanding. Thus, psychiatry does best when skillful clinicians switch between an objectifying medical and neurobiological stance and the interpersonal stance in which the clinician engages the patients as a subject. Attempts to integrate these incommensurate views of patients and their predicaments have historically produced incoherent explanations of psychopathology and have often led treatment astray. For example, privileging of folk psychological testimony, even when filtered through sophisticated theories has historically led psychiatry into intellectually blind and clinically ineffective cul-de-sacs such as psychoanalysis.
Consent for Intensive Care
Authors: Bell Dominic
Published: September 2020

Consent, as the embodiment of respect for autonomy, is considered fundamental to the patient–doctor relationship. The nature of the consent process, as defined by the regulatory bodies and the law, starts with the provision of all information that the patient might consider significant. There is no suggestion that any element of medical care should not be based on these contemporary principles. Intensive care is, however, hard to define in terms of nature, personnel, impact, and outcome, which correspondingly compromises the core foundations of consent. While initiatives are under way to proactively explore and document values and beliefs that might inform subsequent decision making at times when capacity is lost, it is difficult to anticipate that standards of consent applicable to defined medical or surgical treatments will ever be realizable for intensive care. There needs to be broader public, and indeed professional, understanding of the nature and goals of intensive care if all relevant parties are to be confident that the best interests of the individual patient are being met when offering, withholding, delivering, or withdrawing life-sustaining medical treatment.
Refusing and Demanding Medical Treatment in Intensive Care
Authors: Keene Alex Ruck , Fritz Zoë
Published: September 2020

This chapter examines the interactions in England and Wales between adult patients with capacity and the clinical team as regards the refusal of, or requests for, specific treatments. It sets out how to best determine what might constitute harm for that individual patient, and how to appropriately communicate the risks of having (or not having) the treatment. It provides an overview of both the professional guidance and ethical framework in which decisions are made, and the law and how it might constrain (or allow) them to act in certain ways, noting that professional guidance, ethical argument, and the law sometimes pull in different directions, and sometimes inform each other. It also addresses the position of such a patient seeking to project forward their decisions by way of advance decisions to refuse treatment. Co-written by a clinician and a lawyer, and placing the law within the setting of the intensive care unit, the chapter explores the dilemmas that arise when abstract principles meet clinical realities.
Social Media in Intensive Care
Authors: Baruah Rosaleen
Published: September 2020

The use of social media in intensive care has increased steadily since their development in the early 2000s. Usage of social media platforms are now part of everyday life for a sizable proportion of the world’s population. The success of social media relies upon developing a culture where openness and sharing are the norm. This is at odds with traditional medical ethical values such as confidentiality and privacy. Social media can be used for both social and professional purposes, which can lead to unhelpful blurring of lines between personal and professional roles. This chapter discusses guidelines for use of social media for communication purposes by healthcare professionals in the United Kingdom, the benefits and pitfalls of the use of social media for medical education, and the legal aspects of use of social media with respect to intensive care.
OSCE 4
Authors: Hersey Peter , O’Connor Laura , Sams Tom , Sturman Jon
Published: September 2020

Divided into 13 stations on professionalism, resuscitation, data, and equipment, OSCE 4 is mapped to the Fellowship of the Faculty of Intensive Care Medicine (FFICM) and Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) curricula. Structured to reflect the real exam, answers are accompanied by syllabus references for the FFICM and CoBaTrICE domains for self-assessment, along with further reading for self-assessment.
OSCE 6
Authors: Hersey Peter , O’Connor Laura , Sams Tom , Sturman Jon
Published: September 2020

Divided into 13 stations on professionalism, resuscitation, data, and equipment, OSCE 6 is mapped to the Fellowship of the Faculty of Intensive Care Medicine (FFICM) and Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) curricula. Structured to reflect the real exam, answers are accompanied by syllabus references for the FFICM and CoBaTrICE domains for self-assessment, along with further reading for self-assessment.
OSCE 8
Authors: Hersey Peter , O’Connor Laura , Sams Tom , Sturman Jon
Published: September 2020

Divided into 13 stations on professionalism, resuscitation, data, and equipment, OSCE 8 is mapped to the Fellowship of the Faculty of Intensive Care Medicine (FFICM) and Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) curricula. Structured to reflect the real exam, answers are accompanied by syllabus references for the FFICM and CoBaTrICE domains for self-assessment, along with further reading for self-assessment.
Cardiomyopathies
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

The chapter covers heart muscle diseases, starting from the classification and the importance of a cardiomyopathy-focused mindset for diagnostic work up. It goes on to examine genetics, diagnosis, common challenging differentials, and family screening in a number of specific cardiomyopathies in both adults and children. Management of specific cardiomyopathies is discussed in detail, including symptomatic and prognostic treatment with drugs, devices, and surgery, with focus on areas of ongoing debate, such as arrhythmic risk stratification and overlap between dilated and arrhythmogenic cardiomyopathy. In the final section it discusses the pathophysiology, diagnosis, and management of a distinct condition (and arguably not a cardiomyopathy), Takotsubo syndrome.
Inherited arrhythmias and conduction disorders
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

Long QT syndrome is primarily a disorder of repolarization with three principal ion channel currents accounting for the condition. Management revolves around optimization of beta blockade and avoidance of triggers with implantable cardiac defibrillators (ICD) recommended in high risk cases. Brugada syndrome is thought to be caused by Na channel mutations although the aetiology is not fully established. Controversy exists regarding optimal risk stratification approaches. Catecholaminergic polymorphic ventricular tachycardia is caused by abnormalities in calcium handling leading to bidirectional ventricular tachycardia/VF and can be managed using medication –principally beta blockers and occasionally sympathectomy with ICD in cardiac arrest survivors with specific caveats. Inherited conduction disorders should always be considered in patients presenting at a younger age with conduction disease paying specific attention to lamin mutations where an ICD will need to be considered.
Familial hypercholesterolaemia
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

Familial hypercholesterolaemia (FH) is an inborn error of metabolism that leads to accumulation of low-density lipoprotein cholesterol (LDL-C) particles in the blood and premature coronary artery atherosclerosis. This chapter covers the clinical criteria for the diagnosis of FH, the genetics that underpins the condition, cascade testing, premature coronary heart disease, and treatment methods.
Coronary artery disease and myocardial infarction
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

This chapter covers coronary artery disease (CAD) and myocardial infarction, starting with an introduction to the main causal and treatable risk factors for CAD and myocardial infarction, then goes on to discuss the Mendelian disorders associated with CAD (e.g. Tangier disease, sitosterolaemia, etc.) Association studies based on the candidate gene approach are discussed along with genomic studies, e.g. polygenic risk scores.
Stroke
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

Stroke is the third most common cause of death, and the most common cause of disability in developed countries. This chapter examines the genetics of stroke, and single gene causes (although stroke is often just one component of the phenotype). It then describes Anderson—Fabry disease, CADASIL, RVCL, autosomal-dominant porencephaly and infantile hemiparesis, hereditary cerebral haemorrhage with amyloidosis, Moya-Moya disease, sickle cell disease, and MELAS.
The history of rheumatoid arthritis
Authors: Scott David L.
Published: September 2020

The name for rheumatoid arthritis was provided by Alfred Baring Garrod in the late 1850s. Before this period there are descriptions of patients who seem to have had the disease which appeared from the late 1700s onwards, with more descriptions appearing after 1800. Analysis of portraits from the Flemish school of painters have suggested some of these showed features indicative of rheumatoid arthritis. However, the interpretation of the findings in these paintings is highly subjective. There is also some evidence from palaeopathological studies that skeletal remains from several thousand years ago in North America showed features suggestive of rheumatoid arthritis. As with the interpretation of art, this is a relatively subjective field and the findings remain controversial. The key points made in this chapter are that rheumatoid arthritis was definitely present in the nineteenth century and may have been present before them. Whether it is a modern disease or has a long history remains speculative.
Cytokines and other mediators
Authors: Frleta-Gilchrist Marina , McInnes Iain B.
Published: September 2020

Cytokine-mediated pathways are pivotal to the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Since their discovery, cytokine biology has changed the way we understand pathogenetic inflammatory processes, leading to the creation of novel biologic treatments, and transforming patient outcomes. This chapter will elucidate the structure and function of key cytokines that drive autoimmune, inflammatory processes in different stages of RA. In particular, we will describe individual and combinatorial roles of cytokines in adaptive and innate immune cells that promote disease. We will focus especially on critical regulators of RA pathogenesis, such as TNFα‎ and IL-6. Pleotropic effects of cytokines stretch far beyond immune dysregulation, thus precipitating multiple RA comorbidities. Deciphering the individual and combinatorial roles of cytokines is essential to a holistic understanding of RA pathogenesis, in turn, promising to lead to further meaningful clinical and therapeutic discovery.
Clinical features of rheumatoid arthritis
Authors: Mil Annette van der Helm-van
Published: September 2020

The diagnosis of rheumatoid arthritis (RA) is based on a combination of symptoms, signs, and investigation results. As such, it is mainly based on pattern recognition. Classification criteria are not developed to make accurate diagnoses in individual patients, but for the primary purpose of defining homogeneous disease groups for scientific studies. The RA classification criteria have changed over time. This chapter discusses the process of diagnosing RA, the range of clinical characteristics that contribute to this process, its relationship with evolving classification criteria for the condition, and important differential diagnoses. Current recommendations encourage early recognition of arthritis and RA. Since clinical presentation may differ with disease stage, this chapter will also review how the RA phenotype changes as prearthritis progresses to early undifferentiated arthritis and established RA.
Pre-rheumatoid arthritis
Authors: Raza Karim , McGrath Catherine , Boheemen Laurette van , Schaardenburg Dirkjan van
Published: September 2020

The typical evolution of rheumatoid arthritis (RA) is that a person, with genetic risk factors, develops autoantibodies and subclinical inflammation under relevant environmental influences. There are indications that the primary site of the pathology is at mucosal surfaces (e.g. in the gums, lungs, and/or the gut), after which the disease translocates to the joints. Preclinical RA can be defined at the phase during which no clinically apparent features are present (i.e. no symptoms of inflammatory arthritis or clinically apparent joint swelling) but during which RA related biologic derangements such as the presence of autoantibodies are present. This chapter presents an overview of the risk factors, stages, and events occurring during the pre-RA phase. A better understanding of the factors involved will enable more accurate prediction of RA at the individual level and selection of high-risk individuals for inclusion in preventive studies. Several pharmacologic and non-pharmacologic studies aiming to prevent or delay the onset of RA in at-risk individuals are currently underway. It is hoped that such interventions in the pre-RA and indeed in the preclinical-RA phases will allow us to reduce the risk of RA and prevent RA developing in at least a proportion of at-risk patients.
Non-articular manifestations of rheumatoid arthritis
Authors: Macdonald Katherine , Hannah Jennifer , Galloway James
Published: September 2020

Rheumatoid arthritis (RA) is a systemic disease that while primarily affecting joints, can also involve multiple organs of body including the lungs, heart, and blood vessels, bone, muscle, skin, central, and peripheral nervous system, and bone marrow. In addition, RA impacts upon mental health and mood. The process by which extra-articular organs are involved is less well understood than the articular manifestations, but most effects are thought to be driven by similar immune disturbances that drive the disease of the synovium. The 10-year cumulative incidence of any non-articular manifestation is approximately 50%, although severe manifestations are less than 10%. The non-articular manifestations of RA remain a common complication of the disease that account for substantial morbidity and mortality. Annual review of cardiovascular risk factors, bone health, and mental health is important to prevent future morbidity. It is vital to remain vigilant to the development of pulmonary, ocular, infectious, dermatological, or malignant complications. Controlling RA disease burden is the mainstay of management of most extra-articular manifestations, but immunomodulatory therapies come with additional specific risks which include opportunistic infections, malignancies, liver, and haematological abnormalities. Working in close partnership with other specialties is valuable when looking after these complex patients.
Synovial biopsies
Authors: Veale Douglas J. , Fearon Ursula
Published: September 2020

Synovial tissue is the primary tissue inflamed in rheumatoid arthritis. Initial studies of synovial biopsies were obtained during arthroplasty or using a needle to biopsy the joint percutaneously. Recently, small needle arthroscopy or ultrasonography guided techniques have become more widely available to visualize and reliably obtain synovial biopsies. These techniques have allowed significant progress in the study of rheumatoid arthritis pathogenesis, even at the earliest stages of disease. Currently, research efforts are underway to use synovial biopsies to identify patients and to discover biomarkers that will enable clinicians to predict the course of the disease and perhaps to identify more appropriately the correct therapy for patients with rheumatoid arthritis. In this chapter, we describe the advances in synovial tissue biopsy research and how it has improved our knowledge of rheumatoid arthritis pathogenesis, informed our understanding of possible biomarkers for diagnosis and stratification, and potentially may aid in the prediction of disease outcome and response to treatment.
Patient physical function in rheumatoid arthritis
Authors: Gibson Kathryn A. , Pincus Theodore
Published: September 2020

A patient history is far more prominent in diagnosis and management of rheumatoid arthritis (RA) than in many chronic diseases, such as hypertension and diabetes, in which biomarkers dominate clinical decisions. A patient history traditionally has been termed ‘subjective’, based on narrative descriptions, in contrast to ‘objective’ high-technology laboratory and other measures. Self-report questionnaires provide standard, quantitative, reproducible medical history data, which meet criteria for the ‘scientific method’. Patient self-report scores for physical function distinguish active from control treatment results in RA clinical trials as effectively as laboratory tests, joint counts, or indices which include these measures. Self-report physical function generally is more reproducible than joint counts, and more significant than radiographic scores or laboratory tests in the prognosis of severe RA outcomes of work disability and mortality, providing a prognostic indicator analogous to blood pressure or haemoglobin A1C. Four prominent, feasible self-report questionnaires are the Health Assessment Questionnaire (HAQ), its multidimensional version (MDHAQ), the 36-item Short Form (SF-36), and Patient-Reported Outcomes Measurement Information System (PROMIS). The MDHAQ also includes ‘medical’ information (i.e. self-report joint count, symptom checklist, and medical history). Despite documentation of their scientific value and pragmatic advantages to document relevant information while saving time, patient questionnaires remain regarded primarily as providing ancillary rather than essential information to inform clinical decisions, based in part on perceived barriers concerning feasibility and complexities to interface with electronic medical records. Quantitative assessment of physical function on patient questionnaires prior to every routine rheumatology encounter could improve patient care and outcomes.
Tumour necrosis factor inhibitors
Authors: Taylor Peter C. , Narayan Nehal
Published: September 2020

The introduction of biologic TNF inhibitors that neutralize bioactivity of the pro-inflammatory cytokine tumour necrosis factor alpha (TNFα‎) revolutionized the treatment of rheumatoid arthritis (RA). The successful introduction of this class of biologics facilitated subsequent development of multiple targeted biological therapies directed to a range of cytokines and cellular targets involved in RA pathogenesis. However, TNF inhibitors remain the most widely used first-line biologic therapy for RA. In this chapter, we briefly review the contributions of TNF to inflammation and its sequalae in RA. We also outline the known mechanisms of action of biologic TNF inhibitors used in the treatment of RA, the evidence regarding their efficacy and common adverse effects, as well as new developments in this group of therapies.
Interleukin-6 inhibitors
Authors: Hassan Neelam , Choy Ernest
Published: September 2020

Interleukin 6 (IL-6) is a pleiotropic cytokine which has diverse biological activity, with wide-ranging effects on the immune system, homeostasis, and metabolism. It is the most abundant pro-inflammatory cytokine in the synovial joints and sera of patients with active rheumatoid arthritis (RA) and has been found to play a central role in the pathogenesis of the disease, causing joint inflammation and destruction, as well as systemic manifestations. Inhibition of IL-6 signalling has been investigated and developed as a potential treatment strategy for RA. Clinical trials have demonstrated the efficacy and safety of tocilizumab, a humanized monoclonal antibody directed against the IL-6 receptor, showing therapeutic benefit both in early RA and those considered to have refractory disease. The success of tocilizumab has spurred the development of an array of new biologic agents targeting the IL-6 pathway in RA.
Immunogenicity in response to biologic agents
Authors: Jani Meghna , Isaacs John , Strand Vibeke
Published: September 2020

Immunogenicity, or the formation of antidrug antibodies (ADAbs), has been described in response to all biologic therapies licensed for rheumatoid arthritis (RA). In patients treated with monoclonal antibodies, immunogenicity may be associated with low serum drug levels, loss of therapeutic response, poor drug survival, and/or adverse events such as infusion reactions. In this chapter we review the factors that may predispose to immunogenicity to biologics as well as mitigating factors in RA such as the effect of concomitant non-biologic disease-modifying antirheumatic drugs (DMARDs). The reported incidence of ADAbs varies greatly depending on techniques used for measurement. The interpretation of these is discussed followed by the effect of antidrug antibodies and drug levels on drug efficacy and safety of biologics in RA. Finally, we evaluate the evidence to date on the impact of biosimilar switching on immunogenicity and tolerizing to ADAbs.
Adverse events in clinical studies in rheumatoid arthritis
Authors: Yates Mark , Galloway James
Published: September 2020

When prescribing any therapy, potential benefits must be balanced against risk. This is particularly relevant in rheumatoid arthritis (RA), where many treatments available have important associated adverse events. Awareness of adverse event profiles is crucial in supporting patient-centred care, particularly in situations where comparative efficacy data are sparse. In addition, the terminology surrounding adverse events and adverse reactions can be confusing and is often used in a contradictory fashion. Across the biologic class of therapy, head-to-head trials are infrequent, and it is often easier to make choices based on adverse event profile, rather than efficacy. This chapter will review patterns of adverse events seen with RA treatments, including by organ class.
Does elasticity stabilize a magnetic neutron star?
Authors: Bera Prasanta , Jones David Ian , Andersson Nils
Published: September 2020

The configuration of the magnetic field in the interior of a neutron star is mostly unknown from observations. Theoretical models of the interior magnetic field geometry tend to be oversimplified to avoid mathematical complexity and tend to be based on axisymmetric barotropic fluid systems. These static magnetic equilibrium configurations have been shown to be unstable on a short time-scale against an infinitesimal perturbation. Given this instability, it is relevant to consider how more realistic neutron star physics affects the outcome. In particular, it makes sense to ask if elasticity, which provides an additional restoring force on the perturbations, may stabilize the system. It is well known that the matter in the neutron star crust forms an ionic crystal. The interactions between the crystallized nuclei can generate shear stress against any applied strain. To incorporate the effect of the crust on the dynamical evolution of the perturbed equilibrium structure, we study the effect of elasticity on the instability of an axisymmetric magnetic star. In particular, we determine the critical shear modulus required to prevent magnetic instability and consider the corresponding astrophysical consequences.
Effects of Integrase Inhibitor–Based ART on the NLRP3 Inflammasome Among ART-Naïve People With HIV
Authors: Toribio Mabel , Burdo Tricia H , Fulda Evelynne S , Cetlin Madeline , Chu Sarah M , Feldpausch Meghan N , Robbins Gregory K , Neilan Tomas G , Melbourne Kathleen , Grinspoon Steven K , Zanni Markella V
Published: September 2020

The NOD-like receptor protein family pyrin domain containing 3 (NLRP3) inflammasome, activated in the setting of HIV, contributes to pro-atherogenic inflammation. Among antriretroviral therapy–naïve people with HIV (vs controls), levels of caspase-1—a key component of the NLRP3 inflammasome—were significantly increased. Six months of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate significantly decreased caspase-1 levels in association with CD4+/CD8+ ratio recovery.

Trial registration. ClinicalTrials.gov NCT 01766726.
Trends in the Evaluation and Management of Back Pain in Emergency Departments, United States, 2007–2016
Authors: Mullins Peter M , Merriman John Gates , Jaffe Todd A , Mazer-Amirshahi Maryann , Weiner Scott G
Published: September 2020

Objective

 Back pain is one of the most common pain syndromes in the United States, but there has been limited recent description of the role of emergency departments (EDs) in caring for patients with back pain. We investigated trends in the evaluation and management of back pain in U.S. EDs from 2007 to 2016.

Methods

 We performed a retrospective analysis of the National Hospital Ambulatory Medical Care Survey, a nationally representative annual survey of ED visits, which includes data on patient-, hospital-, and visit-level characteristics. We evaluated trends among adult ED visits for back pain, including demographics, resource utilization, and disposition. Trends were assessed through the use of survey-weighted analyses.

Results

 Visit rates as a proportion of overall ED visits were stable from 2007 to 2016 (9.1% [95% confidence interval (CI): 8.5–9.6] vs. 9.3% [95% CI: 8.6–10.0]; P = 0.44). Admission rates declined from 6.4% (95% CI: 5.1–8.0) to 5.0% (95% CI: 3.5–6.9; P < 0.001). Imaging utilization increased from 51.7% (95% CI: 49.3–54.1) to 57.6% (95% CI: 53.3–61.7; P = 0.023), with an increase of 58.3% in computed tomography. Overall opioid utilization declined from 53.5% (95% CI: 49.4–57.5) to 46.5% (95% CI: 43.2–49.8; P < 0.001). Tramadol use increased over the study period (4.1% [95% CI: 3.0–5.8] vs. 8.4% [95% CI: 6.6–10.7]; P < 0.001).

Conclusions

 Opioid utilization during ED visits for back pain decreased from 2007 to 2016, whereas tramadol use more than doubled. Care intensity increased significantly despite declining admission rates. Further research into optimal strategies for back pain management in the ED is needed.
A comparative study of autogenous, allograft and artificial bone substitutes on bone regeneration and immunotoxicity in rat femur defect model
Authors: Zou Wen , Li Xing , Li Na , Guo Tianwei , Cai Yongfu , Yang Xiaoqin , Liang Jie , Sun Yong , Fan Yujiang
Published: September 2020

Repair and reconstruction of large bone defect were often difficult, and bone substitute materials, including autogenous bone, allogenic bone and artificial bone, were common treatment strategies. The key to elucidate the clinical effect of these bone repair materials was to study their osteogenic capacity and immunotoxicological compatibility. In this paper, the mechanical properties, micro-CT imaging analysis, digital image analysis and histological slice analysis of the three bone grafts were investigated and compared after different time points of implantation in rat femur defect model. Autogenous bone and biphasic calcium phosphate particular artificial bone containing 61.4% HA and 38.6% β-tricalcium phosphate with 61.64% porosity and 0.8617 ± 0.0068 g/cm3 density (d ≤ 2 mm) had similar and strong bone repair ability, but autogenous bone implant materials caused greater secondary damage to experimental animals; allogenic bone exhibited poor bone defect repair ability. At the early stage of implantation, the immunological indexes such as Immunoglobulin G, Immunoglobulin M concentration and CD4 cells’ population of allogenic bone significantly increased in compared with those of autologous bone and artificial bone. Although the repair process of artificial bone was relatively inefficient than autologous bone graft, the low immunotoxicological indexes and acceptable therapeutic effects endowed it as an excellent alternative material to solve the problems with insufficient source and secondary trauma of autogenous bone.
Construction of an artificial biosynthetic pathway for hyperextended archaeal membrane lipids in the bacteriumEscherichia coli
Authors: Yoshida Ryo , Hemmi Hisashi
Published: September 2020

Archaea produce unique membrane lipids, which possess two fully saturated isoprenoid chains linked to the glycerol moiety via ether bonds. The isoprenoid chain length of archaeal membrane lipids is believed to be important for some archaea to thrive in extreme environments because the hyperthermophilic archaeon Aeropyrum pernix and some halophilic archaea synthesize extended C25,C25-archaeal diether-type membrane lipids, which have isoprenoid chains that are longer than those of typical C20,C20-diether lipids. Natural archaeal diether lipids possessing longer C30 or C35 isoprenoid chains, however, have yet to be isolated. In the present study, we attempted to synthesize such hyperextended archaeal membrane lipids. We investigated the substrate preference of the enzyme sn-2,3-(digeranylfarnesyl)glycerol-1-phosphate synthase from A. pernix, which catalyzes the transfer of the second C25 isoprenoid chain to the glycerol moiety in the biosynthetic pathway of C25,C25-archaeal membrane lipids. The enzyme was shown to accept sn-3-hexaprenylglycerol-1-phosphate, which has a C30 isoprenoid chain, as a prenyl acceptor substrate to synthesize sn-2-geranylfarnesyl-3-hexaprenylglycerol-1-phosphate, a supposed precursor for hyperextended C25,C30-archaeal membrane lipids. Furthermore, we constructed an artificial biosynthetic pathway by introducing 4 archaeal genes and 1 gene from Bacillus subtilis in the cells of Escherichia coli, which enabled the E. coli strain to produce hyperextended C25,C30-archaeal membrane lipids, which have never been reported so far.
Maternal safety: recent advances and implications for the obstetric anesthesiologist
Authors: Arnolds David E.
Published: September 2020

Purpose of review

Recognition of the increasing maternal mortality rate in the United States has been accompanied by intense efforts to improve maternal safety. This article reviews recent advances in maternal safety, highlighting those of particular relevance to anesthesiologists.

Recent findings

Cardiovascular and other chronic medical conditions contribute to an increasing number of maternal deaths. Anesthetic complications associated with general anesthesia are decreasing, but complications associated with neuraxial techniques persist. Obstetric early warning systems are evolving and hold promise in identifying women at risk for adverse intrapartum events. Postpartum hemorrhage rates are rising, and rigorous evaluation of existing protocols may reveal unrecognized deficiencies. Development of regionalized centers for high-risk maternity care is a promising strategy to match women at risk for adverse events with appropriate resources. Opioids are a growing threat to maternal safety. There is growing evidence for racial inequities and health disparities in maternal morbidity and mortality.

Anesthesiologists play an essential role in ensuring maternal safety. While continued intrapartum vigilance is appropriate, addressing the full spectrum of contributors to maternal mortality, including those with larger roles beyond the immediate peripartum time period, will be essential to ongoing efforts to improve maternal safety.
Biologics in the treatment of Sjogren's syndrome, systemic lupus erythematosus, and lupus nephritis
Authors: Narain Sonali , Berman Nicola , Furie Richard
Published: September 2020

Purpose of review

It is an understatement to say that drug approvals in systemic lupus erythematosus (SLE), lupus nephritis, and Sjogren's syndrome have lagged far behind those in other autoimmune diseases, such as rheumatoid arthritis and psoriatic arthritis. Reasons for this are multiple and include the molecular and clinical heterogeneity of these conditions; confounding by background medications, especially corticosteroids; and clinical trial endpoints. However, the tides are changing, and there have been several bright spots in our attempts to bring more efficacious drugs to our patients.

Recent findings

Several positive phase II and phase III trials in SLE and lupus nephritis with drugs such as anifrolumab, voclosporin, belimumab, and obinutuzumab will no doubt eventually generate regulatory approvals for most, if not all, of these drugs. Although early in development, the promising results in Sjogren's syndrome with iscalimab and ianalumab should make the Sjogren's syndrome community quite hopeful of future drug approvals.

In this review, we highlight recent study results in Sjogren's syndrome, SLE, and lupus nephritis, emphasizing investigational therapies in late stage development, but we also provide a glimpse into drugs of the future.
National Survey of Feeding Tube Verification Practices
Authors: Bourgault Annette M. , Powers Jan , Aguirre Lillian , Hines Robert B. , Sebastian Ansu T. , Upvall Michele J.
Published: September 2020

Background

Harm events such as pneumothoraces and pneumonia continue to be associated with feeding tube insertion. Most bedside verification methods are not accurate to discriminate pulmonary from gastrointestinal system. Evidence-based clinical practice guidelines do not support auscultation of feeding tubes in adults, yet auscultation is the most common method used.

Objectives

Our survey assessed national feeding tube verification practices used by critical care nurses, including progress in auscultation method deimplementation, and stylet reinsertion and cleansing practices.

Methods

A national survey of 408 critical care nurses was performed.

Results

The majority performed auscultation (311 of 408 [76%]) to verify feeding tube placement. In the final multivariable model, nursing education, facility type, observation of colleagues performing auscultation, and awareness of an institutional policy were associated with auscultation of feeding tubes. Thirty-five percent used enteral access devices to verify initial feeding tube placement. Stylet cleansing methods were variable; 38% of reinserted stylets were not cleansed.

Discussion

Minimal progress has been made in deimplementation of auscultation in the past 7 years despite passive knowledge dissemination in research articles, clinical practice guidelines, and procedure manuals. Although pH measure is used as a first-line feeding tube verification method in the United Kingdom, it is rarely used in the United States. Clinical practice guidelines should be updated to incorporate new research on enteral access systems.

Conclusions

Tradition-based practices such as auscultation and certain stylet cleansing methods should be deimplemented. A focused interdisciplinary, multifaceted program is needed to deimplement auscultation practice for adult feeding tubes.
Valvular Heart Disease in Pregnancy
Authors: BORTNICK ANNA E. , LEVINE LISA D.
Published: September 2020

The number of reproductive age women with valvular heart disease is rising and accounts for one third of all heart disease among pregnant women. Severe, symptomatic left-sided cardiac lesions, particularly mitral and aortic stenosis, and mechanical heart valves, are associated with adverse maternal and fetal outcomes. Decreasing maternal and fetal risk requires shared decision-making among patients and the heart team, consisting of obstetricians, maternal-fetal medicine subspecialists, and cardiologists.
Uptake Within Achilles Tendon on Posttherapy Radioiodine Whole-Body Scan Related to Gouty Tophus
Authors: Ehrhart Mark , Tulchinsky Mark , Blacklock Lisa C. , Elojeimy Saeed
Published: September 2020

A 66-year-old man with history of papillary thyroid cancer status post total thyroidectomy underwent 131I-radioiodine ablation. Posttherapy 131I whole-body scan revealed unexpected activity within the left posterior ankle. SPECT/CT localized the radioiodine uptake to a gouty tophus in the Achilles tendon.