bluuebunny/crossref_metadata_2025 huggingface dataset:
ConSpeciFix: classifying prokaryotic species based on gene flow
Authors: Bobay Louis-Marie , Ellis Brian Shin-Hua , Ochman Howard
Published: May 2018

Classification of prokaryotic species is usually based on sequence similarity thresholds, which are easy to apply but lack a biologically-relevant foundation. Here, we present ConSpeciFix, a program that classifies prokaryotes into species using criteria set forth by the Biological Species Concept, thereby unifying species definition in all domains of life.

Availability and implementation

ConSpeciFix’s webserver is freely available at www.conspecifix.com. The local version of the program can be freely downloaded from https://github.com/Bobay-Ochman/ConSpeciFix. ConSpeciFix is written in Python 2.7 and requires the following dependencies: Usearch, MCL, MAFFT and RAxML.
Complex integration of intrinsic and peripheral signaling is required for pituitary gland development†
Authors: Edwards Whitney , Raetzman Lori T
Published: May 2018

The coordination of pituitary development is complicated and requires input from multiple cellular processes. Recent research has provided insight into key molecular determinants that govern cell fate specification in the pituitary. Moreover, increasing research aimed to identify, characterize, and functionally describe the presumptive pituitary stem cell population has allowed for a better understanding of the processes that govern endocrine cell differentiation in the developing pituitary. The culmination of this research has led to the ability of investigators to recapitulate some of embryonic pituitary development in vitro, the first steps to developing novel regenerative therapies for pituitary diseases. In this current review, we cover the major players in pituitary stem/progenitor cell function and maintenance, and the key molecular determinants of endocrine cell specification. In addition, we discuss the contribution of peripheral hormonal regulation of pituitary gland development, an understudied area of research.
Effect of Aerobic Exercise Training and Essential Amino Acid Supplementation for 24 Weeks on Physical Function, Body Composition, and Muscle Metabolism in Healthy, Independent Older Adults: A Randomized Clinical Trial
Authors: Markofski Melissa M , Jennings Kristofer , Timmerman Kyle L , Dickinson Jared M , Fry Christopher S , Borack Michael S , Reidy Paul T , Deer Rachel R , Randolph Amanda , Rasmussen Blake B , Volpi Elena
Published: May 2018

Background

Essential amino acids (EAA) and aerobic exercise (AE) acutely and independently stimulate skeletal muscle protein anabolism in older adults.

Objective

In this Phase 1, double-blind, placebo-controlled, randomized clinical trial, we determined if chronic EAA supplementation, AE training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis.

Methods

We phone-screened 971, enrolled 109, and randomized 50 independent, low-active, nonfrail, and nondiabetic older adults (age 72 ± 1 years). We used a 2 × 2 factorial design. The interventions were: daily nutritional supplementation (15 g EAA or placebo) and physical activity (supervised AE training 3 days/week or monitored habitual activity) for 24 weeks. Muscle strength, physical function, body composition, and muscle protein synthesis were measured before and after the 24-week intervention.

Results

Forty-five subjects completed the 24-week intervention. VO2peak and walking speed increased (p < .05) in both AE groups, irrespective of supplementation type, but muscle strength increased only in the EAA + AE group (p < .05). EAA supplementation acutely increased (p < .05) muscle protein synthesis from basal both before and after the intervention, with a larger increase in the EAA + AE group after the intervention. Total and regional lean body mass did not change significantly with any intervention.

Conclusions

In nonfrail, independent, healthy older adults AE training increased walking speed and aerobic fitness, and, when combined with EAA supplementation, it also increased muscle strength and EAA-stimulated muscle protein synthesis. These increases occurred without improvements in muscle mass.
De novo genome assembly of the red silk cotton tree (Bombax ceiba)
Authors: Gao Yong , Wang Haibo , Liu Chao , Chu Honglong , Dai Dongqin , Song Shengnan , Yu Long , Han Lihong , Fu Yi , Tian Bin , Tang Lizhou
Published: May 2018

Background

Bombax ceiba L. (the red silk cotton tree) is a large deciduous tree that is distributed in tropical and sub-tropical Asia as well as northern Australia. It has great economic and ecological importance, with several applications in industry and traditional medicine in many Asian countries. To facilitate further utilization of this plant resource, we present here the draft genome sequence for B. ceiba.

Findings

We assembled a relatively intact genome of B. ceiba by using PacBio single-molecule sequencing and BioNano optical mapping technologies. The final draft genome is approximately 895 Mb long, with contig and scaffold N50 sizes of 1.0 Mb and 2.06 Mb, respectively.

Conclusions

The high-quality draft genome assembly of B. ceiba will be a valuable resource enabling further genetic improvement and more effective use of this tree species.
Increased likelihood of induced seismicity in highly overpressured shale formations
Authors: Eaton David W , Schultz Ryan
Published: May 2018

Fluid-injection processes such as disposal of saltwater or hydraulic fracturing can induce earthquakes by increasing pore pressure and/or shear stress on faults. Natural processes, including transformation of organic material (kerogen) into hydrocarbon and cracking to produce gas, can similarly cause fluid overpressure. Here, we document two examples from the Western Canada Sedimentary Basin where earthquakes induced by hydraulic fracturing are strongly clustered within areas characterized by pore-pressure gradient in excess of 15 kPa m−1. Despite extensive hydraulic-fracturing activity associated with resource development, induced earthquakes are virtually absent in the Montney and Duvernay Formations elsewhere. Statistical analysis suggests a negligible probability that this spatial correlation developed by chance. This implies that, in addition to known factors such as anthropogenic pore-pressure increase and proximity to critically stressed faults, high in situ overpressure of shale formations may also represent a controlling factor for inducing earthquakes by hydraulic fracturing. On a geological timescale, natural pore-pressure generation may lead to fault-slip episodes that regulate the magnitude of formation overpressure.
Statistical Genetics
Authors: Andlauer Till F. M. , Müller-Myhsok Bertram , Ripke Stephan
Published: May 2018

Over more than the last decade, hypothesis-free genome-wide association studies (GWAS) have been widely used to detect genetic factors influencing phenotypes of interest. The basic principle of GWAS has been unchanged since the beginning: a series of univariate tests is conducted on all genetic variants available across the genome. We present study designs and commonly used methods for genome-wide studies, with a focus on the analysis of common variants. The basic concepts required for an application of GWAS in psychiatric genetics are introduced, from power calculation to meta-analysis. This chapter will help the reader in gaining the knowledge required for participation in and realization of GWAS of both qualitative and quantitative traits.
The Role of Copy Number Variation in Psychiatric Disorders
Authors: Rees Elliott , Kirov George
Published: May 2018

Copy number variants (CNVs) are deletions, duplications, inversions, or translocations of large DNA segments. They can play a significant role in human disease. Thirteen CNVs have received strong statistical support for involvement in schizophrenia. They are all rare in cases (<1%), much rarer among controls, and have high odds ratios (ORs) for causing disease. The same CNVs also increase risk for autism spectrum disorders, developmental delay, and medical/physical comorbidities. The penetrance of these CNVs for any disorder is relatively high, ranging from 10% for 15q11.2 deletions to nearly 100% for deletions at 22q11.2. Strong selection pressure operates against carriers of these CNVs. Most of these are formed by non-allelic homologous recombination (NAHR), which leads to high mutation rates, thus maintaining the rates of these CNVs in the general population, despite the strong selection forces.
Imaging Genetics
Authors: Dixson Luanna , Tost Heike , Meyer-Lindenberg Andreas
Published: May 2018

Imaging genetics is the study of how modifications of the DNA sequence may manifest in altered brain structure, function, and biochemistry. This field has been made possible through the combined analysis of genotyping and neuroimaging data in the same individual. Imaging genetics has had an especially significant impact in the realm of psychiatry, where the identification of genetic variants associated with heritable “intermediate phenotypes” provides important clues about underlying molecular mechanisms. More recently, integration of information on biological pathways, protein interactions, epigenetic factors, and gene expression has provided a holistic framework for developing biologically driven hypotheses of gene effects in the brain. This chapter gives a historical perspective on the imaging genetics approach, outlines a few key examples, and speculates on future directions for this exciting discipline.
Postcraniotomy Pain and Chiari Malformation Pain
Authors: Wuenstel Andrew , Frim David , Anitescu Magdalena
Published: May 2018

The clinical syndrome associated with Chiari malformation type 1 (CM1) affects all ages, newborns through elderly. Boys and girls are affected equally; adult women are affected three times more than men. The most common form of Chiari malformation, CM1, is often asymptomatic, but one common symptom of CM1 is occipital headache triggered by Valsalva maneuvers. A syrinx, present in many patients, causes neurologic deficits at the level of the syrinx or below. There are medical and surgical management options to treat the pain syndromes associated with CM1. For patients who are resistant to medical and interventional therapy after surgical decompression, few efficacious treatments are available to relieve chronic postoperative, postcraniotomy pain.
Fibromyalgia
Authors: Jan Reem , Zhang Dawen
Published: May 2018

Fibromyalgia is caused by abnormal central pain processing, but it is often dismissed as a psychiatric or functional disorder. Perimenopausal women are most commonly affected, but the incidence in men has been underestimated. Patients present with diffuse musculoskeletal pain and frequently have sleep disturbances, fatigue, and somatic complaints. In 2010, the American College of Rheumatology removed the need for a standardized tender point examination. The disease is often misdiagnosed given its nonspecific complaints and heterogeneous presentation. Laboratory testing is used only to rule out differential diagnoses. Treatment is challenging and a multidisciplinary approach, including patient counseling and education, a graded exercise program, and pharmacologic treatment, is recommended.
Acute Pain in the Opioid-Tolerant Patient
Authors: Badiola Ignacio , Singh Tulsi , Liu Jiabin , Elkassabany Nabil
Published: May 2018

The number of people addicted to prescription and illicit opioids continues to increase, and many of these patients present to the hospital or pain center with acute pain issues. The matter is further complicated by the increasing number of patients with legitimately painful conditions treated with chronic opioid therapy. Typically, these patients are difficult to manage during any acute pain episode due to their opioid tolerance and opioid-induced hyperalgesia. This difficulty often leads to inadequate pain management, increased suffering, and delayed hospital discharge. Increased awareness is needed among pain management physicians and other clinicians who care for opioid-tolerant patients, yet there is a lack of evidence-based medicine regarding the optimal treatment of this population.
Fluoxetine, Comprehensive Cognitive Behavioral Therapy, and Placebo in Generalized Social Phobia
Authors: Habecker Erin , Wasser Tobias
Published: May 2018

This chapter provides a summary of a landmark study on anxiety disorders. For generalized social phobia, are fluoxetine and comprehensive cognitive behavioral therapy efficacious? How do their efficacies compare? And is there an advantage to combination therapy? Starting with these questions, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. Results of the study indicate that fluoxetine and comprehensive cognitive behavioral therapy are superior to placebo for the treatment of generalized social phobia; neither treatment is superior to the other and there is no apparent advantage to combination therapy. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
Mood Stabilizer Monotherapy versus Adjunctive Antidepressant for Bipolar Depression
Authors: De Aquino João Paulo , Beech Robert
Published: May 2018

This chapter provides a summary of a landmark study on bipolar disorder, which aims to address the following question: In patients with bipolar disorder receiving mood-stabilizing agents, does adjunctive antidepressant therapy reduce the symptoms of bipolar depression without increasing the risk for mania? Starting with that question, the chapter describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints and results, in addition criticisms and limitations. Subsequently, other relevant studies are briefly reviewed and their clinical implications are discussed. Finally, a relevant clinical exemplifies the application of the current evidence behind the clinical question addressed by the study.
The Long-Term Natural History of Bipolar I Disorder
Authors: Engler Zachary , Beech Robert
Published: May 2018

This chapter provides a summary of a landmark study on bipolar disorder. What is the natural progression of symptoms in patients with bipolar I disorder? Overall, how long do people with bipolar I disorder spend with depressive, manic, or other affective symptoms versus periods of euthymia, without controlling treatment modality? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
The Multimodal Treatment Study of Children with Attention Deficit/Hyperactivity Disorder (MTA)
Authors: Hochman Michael H.
Published: May 2018

This chapter provides a summary of a landmark study in child and adolescent psychiatry. What is the most effective long-term management strategy in children with attention-deficit/hyperactivity disorder: medication management, behavioral treatment, a combination of medication management and behavioral treatment, or routine community care? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
Adolescents with SSRI-Resistant Depression
Authors: Tobon Amalia Londono , Stevens Hanna E.
Published: May 2018

This chapter provides a summary of a landmark study in child and adolescent psychiatry addressing the common clinical experience of an adolescent that does not respond to initial antidepressant treatment. Should adolescents with selective serotonin reuptake inhibitor (SSRI) resistant depression be switched to another SSRI or to venlafaxine with or without cognitive behavioral therapy? Starting with that question, it describes the basics of the study, including funding, study locations, who was studied, how many patients, study design, study interventions, follow-up, endpoints, results, and criticism and limitations. This chapter also briefly reviews other relevant studies and information, discusses implications of the findings, and concludes with a relevant clinical case scenario and suggested management for the case.
Global Burden of Mental and Substance Use Disorders
Authors: Yarnell Stephanie , Edens Ellen
Published: May 2018

This chapter provides a summary of a landmark study in epidemiology. The Global Burden of Disease Study was a ground breaking venture in answering the question regarding the prevalence of various diseases. By analyzing this database, the current study was sought to determine the burden of disease attributable to mental and substance use disorders. With this in mind, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
Meta-Analysis of the Dose–Response Relationship of SSRIs in Adult Patients with Obsessive-Compulsive Disorder
Authors: Yuen Eunice , Bloch Michael H.
Published: May 2018

This chapter provides a summary of a landmark study on adult patients with obsessive-compulsive disorder (OCD). Discussion here is based on a meta-analysis from nine prominent clinical studies. Are there any differences in efficacy and tolerability among different doses of, selective serotonin reuptake inhibitor in the treatment of OCD? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and American Psychiatry Association (APA) guideline information, discusses implications, and concludes with a relevant clinical case.
QTc-Interval Abnormalities and Psychotropic Drug Therapy in Psychiatric Patients
Authors: Sun Amanda , Srihari Vinod H.
Published: May 2018

This chapter provides a summary of a landmark study on schizophrenia and the impact of demographic factors and psychotropic medications on markers of risk for cardiac events. Is QTc prolongation associated with specific psychotropic medications, the dose, or other factors? What is the correlation between other QT or T-wave abnormalities and these factors? Starting with these questions, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death
Authors: Hicks Hamilton , Tek Cenk
Published: May 2018

This chapter provides a summary of a landmark study on schizophrenia. The study authors sought to compare the safety of typical and atypical antipsychotics with regard to a fatal adverse event. Are atypical antipsychotic drugs associated with a lower risk of sudden cardiac death compared to typical antipsychotics? Starting with that question, this chapter describes the basics of the study, including the funding source, study location, who was studied, how many patients, study design, study intervention, follow-up, study endpoints, results, as well as criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
Clozapine for Suicidality in Schizophrenia
Authors: Barron Daniel , Capurso Noah
Published: May 2018

Patients with schizophrenia have a 50% risk of a suicide attempt during their life, with a nearly an estimated 10% risk of completed suicide. Decreasing this risk is an urgent clinical concern. This chapter provides a summary of a landmark study on how to reduce suicidality in patients with schizophrenia, specifically whether clozapine reduces suicidal events in patients with schizophrenia. This chapter describes the outline of the study, including fundings sources, study locations, the patient population and how many were studied, the study design and intervention through to follow-up, endpoints, results, and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence
Authors: Johnson Kevin , Muvvala Srinivas
Published: May 2018

This chapter provides a summary of the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence Study. This landmark study researches the efficacy of medications, behavioral therapies, and their combinations in the treatment of alcohol use disorder. Starting with the research question, this review describes the basics of the study, including funding, study location, who was studied, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. One key finding is the efficacy of naltrexone at lowering the number of heavy alcohol consumption days. The chapter briefly reviews other relevant studies and information, discusses implications, provides clinical guidelines, and concludes with a relevant clinical case.
Foundations of Perinatal Genetic Counseling
Authors: Mathiesen Amber , Roy Kali
Published: May 2018

Foundations of Perinatal Genetic Counseling provides an overview of the core concepts needed to practice perinatal genetic counseling, including the basics of pregnancy, the genetic counseling appointment, family and pregnancy history, prenatal screening, prenatal diagnosis, common indications, carrier screening, management of high-risk pregnancy, assisted reproductive technology, preimplantation genetic screening and diagnosis, and common situations arising in perinatal genetic counseling. It discusses general obstetrical information as it pertains to perinatal genetic counseling, including topics such as calculating gestational age, understanding gravidity and parity, and reproductive options. This book reviews the key components of a perinatal genetic counseling session and how to take a perinatal family, medical, and pregnancy history, as well as a prenatal risk evaluation based on age, family and pregnancy history, testing results, and ultrasound findings. It includes a detailed description of both prenatal screening and diagnostic testing options, including maternal serum screening, cell-free DNA testing, amniocentesis, and chorionic villus sampling. It also provides an explanation of carrier testing, including methods of testing, types of conditions, and indications for testing. This text provides information on the indications for referral to a perinatal genetic counselor such as age-related risks, personal and family history, ultrasound anomalies, teratogen exposure, recurrent pregnancy loss, and preconception counseling. It also reviews the management and types of referrals made in a high-risk pregnancy. Assisted reproductive technology is reviewed as well as descriptions of preimplantation genetic diagnosis and screening. It also describes common psychosocial and ethical situations encountered in perinatal genetic counseling.
The Perinatal Genetic Counseling Appointment and Family History
Authors: Mathiesen Amber , Roy Kali
Published: May 2018

This chapter on the perinatal genetic counseling appointment and the documentation of a family history outlines the basic components of the perinatal genetic counseling session as well as some considerations when taking a family history that are particularly relevant to the perinatal setting. The chapter reviews the fundamental components of the perinatal genetic counseling session. It discusses specific details on how to obtain a pregnancy history and family history, as well as how to interpret those histories. Last, it discusses unique situations that may arise in the perinatal setting when taking a pregnancy and family history, including gamete donation, same-sex couples, surrogacy, adoption, and ethnicity.
Prenatal Diagnosis
Authors: Mathiesen Amber , Roy Kali
Published: May 2018

Prenatal diagnosis is the term used to describe a set of tests that are designed to determine whether a specific genetic condition is present in a fetus. This chapter provides a detailed description of procedures as well as the types of testing options available for prenatal diagnosis. The two techniques for prenatal diagnosis, amniocentesis and chorionic villus sampling, are described in detail, including their procedures, risks, limitations, and their use in twin gestations. The prenatal diagnosis testing options are also described in detail, including karyotype, fluorescence in situ hybridization (FISH), microarray, molecular testing, and alpha-fetoprotein (AFP) and acetylcholinesterase (AChE) level testing. The chapter also includes images of karyotype, FISH, and microarray test results, and it also reviews the indications for prenatal diagnostic testing.
Common Indications
Authors: Mathiesen Amber , Roy Kali
Published: May 2018

This chapter describes common reasons for referral to a perinatal genetic counselor including age-related risks, personal and family history, ultrasound anomalies, teratogen exposure, recurrent pregnancy loss, and preconception counseling. Maternal and paternal age-related pregnancy risks are described, such as aneuploidy, single-gene conditions, and autism. A referral for a personal and/or family history of various conditions including single-gene conditions, aneuploidy, multifactorial conditions, birth defects, intellectual disability, developmental delay, autism, and consanguinity is described. The chapter reviews ultrasound anomalies and describes common ultrasound findings associated with aneuploidy, and hallmark ultrasound findings associated with particular genetic conditions, as well as identification of open neural tube defects. Teratogen exposure during pregnancy is discussed, including timing, dose, and duration and a description of typical features and symptoms associated with common teratogens. The chapter reviews the evaluation of pregnancy loss and stillbirth, male and female infertility, and referral for preconception counseling.
Carrier Screening
Authors: Mathiesen Amber , Roy Kali
Published: May 2018

This chapter provides information on carrier screening options available, including testing based on ethnicity, targeted to the family history or clinical situation, or by use of expanded carrier testing panels. It describes who should be offered testing, the timing of testing, how to evaluate the risks of conditions being tested, and how to interpret results, in addition to providing a brief description of newborn screening. The chapter describes testing protocols for specific conditions including cystic fibrosis, spinal muscular atrophy, FMR-1–related conditions, and hemoglobinopathies. It reviews ethnicity-based screening, as in Ashkenazi Jewish and French Canadian populations, as well as screening when there is a family history. It also discusses the use, benefits, and recommendations when offering expanded carrier screening.
Assisted Reproductive Technology and Reproductive Options for the At-Risk Couple
Authors: Mathiesen Amber , Roy Kali
Published: May 2018

For those with an increased risk of having a child with a genetic condition, reproductive options include avoiding pregnancy altogether, undertaking prenatal diagnosis in a current pregnancy, and preventing the transmission of the genetic changes responsible for the condition to a child. This chapter on assisted reproductive technology and reproductive options for the at-risk couple describes the basic techniques of assisted reproductive technologies as well as reproductive testing options prior to in vitro fertilization, including preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). It includes a brief overview of ovarian stimulation, intrauterine insemination (IUI), and in vitro fertilization. This chapter discusses the details of PGS including the process and its limitations. It also includes a discussion of PGD, including the process, such as linkage analysis, and limitations, such as allele dropout.
Common Perinatal Genetic Counseling Situations
Authors: Mathiesen Amber , Roy Kali
Published: May 2018

This chapter highlights common situations in perinatal counseling, including challenging circumstances, complex situations, and ethical dilemmas. It discusses conflicts that may arise from pregnancy termination; the complexities surrounding the identification of incidental findings such as misattributed paternity, discovery of consanguinity, or discovery of an incidental condition; and issues surrounding privacy and confidentiality, including familial implications of genetic knowledge. Also discussed are difficult circumstances such as couples in conflict or nonparticipation of a male partner and dealing with uncertainty in various situations including fetal diagnosis and prognosis, family history, complex conditions, and variants of uncertain significance. Conflicts around fetal sex determination and the disclosure of adult-onset conditions are discussed, as is the situation when a patient asks for provider guidance in making a decision. Barriers to the consenting process are discussed, as are the complexities of practicing in a field of rapidly evolving technologies.
Neurocritical Care Pharmacotherapy
Authors: Wijdicks Eelco F.M. , Clark Sarah L.
Published: May 2018

Drugs are used to treat, salvage, and protect the brain. This book provides information on how to prescribe and monitor the drugs most frequently used in the emergency department and the neurosciences critical care unit. Each drug is discussed in great detail to allow for its efficient use and to allow the recognition of drug-related problems. The book explains how these drugs work and what the body does with the drug in the acutely ill neurologic patient. It provides guidance on how these drugs are best administered and revisits how we can most effectively practice medication reconciliation. This manual has multiple useful concise tables and graphs summarizing over 150 drugs.
Drug Delivery, Monitoring, and Interactions
Authors: Wijdicks Eelco F. M. , Clark Sarah L.
Published: May 2018

This chapter outlines the typical pathway of an administered drug and the factors that affect it. The main components that determine a drug’s pharmacokinetics and pharmacodynamics are discussed. Issues important for the physician such as Pharmacokinetic parameters, drug administration routes, and principles of drug interactions are highlighted. Problems with inadvertently holding home or maintenance medications and other drug errors are outlined. Pharmacogenomics and its emerging clinical relevance is introduced.
Agitation and Delirium
Authors: Wijdicks Eelco F. M. , Clark Sarah L.
Published: May 2018

Delirium involves abnormalities in perception and in attention with failure of the caregiver to correct or recognize behavior. Marked agitation disturbs the patient’s orientation, attention, and sleep. The effects of uncontrolled agitation are manifold and not in the least causing bodily harm. In intensive care units, agitation and delirium occur in the sickest patients. Treatment of delirium is necessary and needed early after recognition. In this chapter, the best pharmacologic approaches and indications are discussed, including neuroleptics. Atypical antipsychotics are the first-line treatment for delirium. Recognition of delirium starts with the nursing staff and the identification of medications that are associated with triggering delirium.
Antiepileptic Drugs
Authors: Wijdicks Eelco F. M. , Clark Sarah L.
Published: May 2018

Patients are often admitted to the neurosciences intensive care unit specifically for the treatment of a series of seizures or focal status epilepticus. Far more urgent is convulsive status epilepticus, which requires multiple intravenously administered antiepileptic drugs. The choices are different when the patient is in status epilepticus and refractoriness is mostly due to pharmacologic resistance. Use of an algorithm for decision making is common in the management of refractory status epilepticus. Antiepileptic drugs often interact with other antiepileptic drugs. This chapter discusses the use of antiepileptic drugs available to treat seizures, recurrent seizures, status epilepticus, and refractory status epilepticus.
Antimicrobial Therapy for Central Nervous System Infections
Authors: Wijdicks Eelco F. M. , Clark Sarah L.
Published: May 2018

Broad-spectrum antibiotics—those that are bactericidal and able to penetrate the blood–brain barrier—must be administered to any patient with a suspected infection of the central nervous system (CNS). Antimicrobials should be selected with consideration of spectrum of activity, pharmacokinetics, mechanism of action, and need to be administered in a timely fashion. This chapter discusses antibiotics that provide good penetration of the central nervous system, and appropriate doses for these infections are outlined. Antiviral therapy for CNS infections is limited but complex. Antimicrobial therapy for fungal meningitis is well defined but rarely indicated. Understanding the spectrum of antimicrobials and dosing is essential knowledge in caring for patients in the neurosciences intensive care unit with CNS infections.
Eugen Bleuler
Authors: Shorter Edward , Fink Max
Published: May 2018

Eugen Bleuler, professor of psychiatry in Zurich, renamed Kraepelin’s dementia praecox as “schizophrenia” in 1908. He retained catatonia as a subtype. Bleuler’s dementia praecox was a much milder and broader condition than the downhill course toward dementia that Kraepelin had described: it could strike at any moment in life, not just in youth, and often ended in partial recovery. Ultimately, Kraepelin’s and Bleuler’s efforts gave rise to an immense “schizophrenia” literature, an industry that continues today, an outpouring that can be compared only to the enormous “hysteria” industry that existed before DSM-III abolished the diagnosis in 1980. The effect is striking: one moment the profession believes implicitly in a disease so huge as to dominate the literature; the next moment the disease no longer exists.
Delirious Mania and Febrile Catatonia
Authors: Shorter Edward , Fink Max
Published: May 2018

The acute onset of excited, aggressive, and destructive states, often febrile, described as Bell’s mania and Stauder’s delirium are hallmarks in the literature. Death is frequent. Subjects are disoriented, and delirious with catatonia signs of mutism, posturing, and repetitive speech. Treatments were ineffective until multiple daily induced seizures (ECT) were shown to be life-saving. A syndrome of nostalgia was also described in French and German armies among subjects pining to death. Delirious mania and its fatal variants were a rock-solid part of traditional psychiatric diagnosis. By the 1960s, almost everywhere in the UK and Europe, fatal delirious mania or pernicious catatonia was an accepted part of psychiatric diagnostics that a clinician would ignore at the patient’s peril.
L’Envoi
Authors: Shorter Edward , Fink Max
Published: May 2018

The long history of catatonia is presently resolved into a systemic syndrome, identified by symptoms and signs, verified by tests, and fully resolved by defined means. Our skills in relieving catatonia are as successful as our treatment for neurosyphilis. Catatonia is best seen as a systemic medical, not a psychiatric disorder. Unresolved fear is a core feature in its pathophysiology. There are difficulties distinguishing catatonia from melancholia; the prompt resolution of both with induced seizures presents a challenge in understanding them. Are they related? Melancholia’s neuroendocrine abnormalities offer direction to neuroscience studies of catatonia and of the mechanism of electroconvulsive therapy (ECT).
Neuroendocrine system
Authors: Straub Rainer H.
Published: May 2018

Endocrine abnormalities are very common in patients with chronic autoimmune rheumatic diseases (CARDs) due to the systemic involvement of the central nervous system and endocrine glands. In recent years, the response of the endocrine (and also neuronal) system to peripheral inflammation has been linked to overall energy regulation of the diseased body and bioenergetics of immune cells. In CARDs, hormonal and neuronal pathways are outstandingly important in partitioning energy-rich fuels from muscle, brain, and fat tissue to the activated immune system. Neuroendocrine regulation of fuel allocation has been positively selected as an adaptive programme for transient serious, albeit non-life-threatening, inflammatory episodes. In CARDs, mistakenly, the adaptive programmes are used again but for a much longer time leading to systemic disease sequelae with endocrine (and also neuronal) abnormalities. The major endocrine alterations are depicted in the following list: mild activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, inadequate secretion of ACTH and cortisol relative to inflammation, loss of androgens, inhibition of the hypothalamic-pituitary-gonadal axis and fertility problems, high serum levels of oestrogens relative to androgens, fat deposits adjacent to inflamed tissue, increase of serum prolactin, and hyperinsulinaemia (and the metabolic syndrome). Neuroendocrine abnormalities are demonstrated using this framework that can explain many CARD-related endocrine disturbances. This chapter gives an overview on pathophysiology of neuroendocrine alterations in the context of energy regulation.
The eye
Authors: Petrushkin Harry , Rogers Duncan , Stanford Miles
Published: May 2018

The ophthalmologist has a large part to play in the management of many rheumatological diseases. These diseases can cause a number of symptoms from mild ocular discomfort to sudden blindness. In addition, many rheumatological diseases have helpful ophthalmic signs, which can aid diagnosis.
This chapter has been written to help rheumatologists identify these signs and symptoms. We have started by summarizing the common pathology found in patients with rheumatological diseases (dry eye syndromes, conjunctivitis, episcleritis, scleritis, uveitis, and optic neuropathy). This has been arranged working backwards from the front of the eye towards the retina and optic nerve. The rheumatological conditions that give rise to ophthalmic signs (giant cell arteritis, systemic lupus erythematosus, polyarteritis nodosa, Wegner’s granulomatosis, systemic sclerosis, rheumatoid arthritis, seronegative arthropathies, sarcoidosis, and Behçet’s disease) have then been summarized, including a section of paediatric conditions (juvenile idiopathic arthritis, spondyloarthropathies, and multisystemic illness). Finally, treatment regimes and recent guidelines have been covered for the screening of uveitis in juvenile idiopathic arthritis and the management of patients taking hydroxychloroquine.
We hope that both rheumatologists in training and consultants find this chapter a useful clinical aid, and that it encourages them to look closely for subtle signs that will help improve the management of their patients.
Genetics of spondyloarthropathies
Authors: Brown Matthew
Published: May 2018

Spondyloarthropathies are a diverse group of conditions, of which ankylosing spondylitis is the prototypic disease, with shared clinical features, genetic risk factors, and histopathological characteristics. These conditions are highly familial and heritable. Several genes have been associated with spondyloarthropathies, with genes in the IL-23 signalling pathway being shared by the major types of spondyloarthritis. These discoveries have already led to the development and successful clinical introduction of novel treatments for psoriasis and psoriatic arthritis, and major advances in our understanding of the pathogenesis of the conditions. Many more genes remain to be identified which are involved in these common conditions; identifying these genes is likely to be highly informative as to their causes.
Skeletal muscle physiology and damage
Authors: Dinser Robert , Müller-Ladner Ulf
Published: May 2018

This chapter summarizes muscle structure and physiology, the genesis and adaptions of muscle throughout life, and clinical assessment of muscle disease. The anatomical and molecular structure of muscle tissue is described, as well as the basic function of the neuromuscular junction, the energy metabolism of muscle tissue, and the mechanisms of fatigue. Key elements of embryological myogenesis, the adaptions of muscle to exercise and damage, and physiological ageing are depicted. A summary of the clinical analysis of muscle function including laboratory, electrophysiological, and imaging testing is provided.
Alternative therapies
Authors: Ernst Edzard
Published: May 2018

Alternative therapies are used by many patients suffering from rheumatic conditions. In this chapter, the efficacy and safety of various forms of alternative medicine will be discussed based on the evidence from clinical trials and systematic reviews. The following treatments will be considered: acupuncture, Ayurvedic medicine, chiropractic, dietary supplements, herbal remedies, homeopathy, massage, osteopathy, t’ai chi, and yoga.
Perioperative management of immunosuppression
Authors: Carmona Loreto , Galindo Maria , Martin Maria
Published: May 2018

Many rheumatologists are concerned about the complications of maintaining immunosuppression at the time of elective surgery. Complications may be increased risk of infection, or a slow healing of the surgical wound. On the other hand, stopping medication may place the patient at undesirable levels of disease activity. Many rheumatologists actually act on art, stopping the drug perioperatively depending on blood count, drug type and dose, previous postoperative complications, type of surgery, and other factors. The timing of stopping treatment preoperatively and restarting after surgery also significantly differ among rheumatologists. All in all, there is a great variability in clinical practice related to the perioperative use of immunosuppressants.
This chapter reviews the evidence on methotrexate, glucocorticoids, and biological therapies related to the perioperative period, and it proposes some recommendations on the management of immunosuppressant drugs in rheumatic diseases. Factors that may be related to complications will also be reviewed.
Axial spondyloarthritis
Authors: Poddubnyy Denis , Sieper Joachim
Published: May 2018

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly of the sacroiliac joint (SIJ) and the spine. It starts normally in the second decade of life and has a slight male predominance. The prevalence is between 0.2% and 0.8% and is strongly dependent on the prevalence of HLA-B27 in a given population. AxSpA can be split in patients with radiographic axSpA (also termed ankylosing spondylitis (AS)) and in patients with non-radiographic axSpA (nr-axSpA). For the diagnosis of AS, the presence of radiographic sacroiliitis is mandatory. However, radiographs do not detect active inflammation but only structural bony damage. Most recently new classification criteria for axSpA have been developed by the Assessment of Spondylo-Arthritis International Society (ASAS) which cover AS but also the earlier form of nr-axSpA. MRI has become an important new tool for the detection of subchondral bone marrow inflammation in SIJ and spine and has become increasingly important for an early diagnosis. HLA-B27 plays a central role in the pathogenesis but its exact interaction with the immune system has not yet been clarified. Besides pain and stiffness in the axial skeleton patients suffer also from periods of peripheral arthritis, enthesitis, and uveitis. New bone formation as a reaction to inflammation and subsequent ankylosis of the spine determine long-term outcome in a subgroup of patients. Currently only non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF) blockers have been proven to be effective in the medical treatment of axial SpA, and international ASAS recommendations for the structured management of axial SpA have been published based on these two types of drugs. Conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate are not effective.
Reactive arthritis and enteropathic arthropathy
Authors: Gaston J. S. Hill
Published: May 2018

Reactive arthritis (ReA), and enteropathic arthritis secondary to inflammatory bowel disease, are forms of spondyloarthritis, all of which share an association with HLA B27 and can involve both axial and peripheral joints. Genetic studies strongly implicate the cytokines IL-17 and IL-23 in their pathogenesis, and evidence for autoimmunity is lacking. ReA is triggered by particular bacteria, mainly affecting the gut and genitourinary tract, though infections are sometimes asymptomatic. Classically an acute oligo- or monoarthritis with enthesitis occurs, often with inflammatory back pain, though mild polyarthritis can also occur. Septic and crystal-induced arthritis are the principal differential diagnoses. Extra-articular features may aid diagnosis, which otherwise requires laboratory evidence of preceding infection. Bacterial components traffic to the joint (which is nevertheless sterile), and elicit local pro-inflammatory immune responses. Most ReA is self-limiting, but persistent cases may require disease-modifying anti-rheumatic drugs or even biologics.
Sjögren’s syndrome—clinical features
Authors: Bowman Simon , Hamburger John , Price Elizabeth , Rauz Saaeha
Published: May 2018

Sjögren’s syndrome is a chronic, immune-mediated, condition of unknown aetiology characterized by focal lymphocytic infiltration of exocrine glands associated with dry mouth and eyes. It occurs in its own right (primary Sjögren’s syndrome, pSS), or as a late feature of other rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma (secondary Sjögren’s syndrome).
There is a strong female bias. pSS typically affects women in their middle years with an estimated prevalence of 0.1–0.6%. 75% of patients have anti-Ro and/or anti-La antibodies, often with raised immunoglobulin levels (hypergammaglobulinaemia). In patients without these antibodies the diagnosis can be confirmed by salivary gland biopsy.
Treatment is generally symptomatic using artificial tears, saliva replacements/stimulants and good dental hygiene. Three-quarters of patients with pSS report significant fatigue with a negative impact on quality of life. This can be the most disabling symptom. Approximately 20% of patients develop systemic features including persistent salivary gland swelling, cutaneous vasculitis, peripheral neuropathy, interstitial lung disease, autoimmune cytopenias or renal tubular acidosis. Hydroxychloroquine and corticosteroids are the most widely used therapies for systemic features.
There is a 44fold increased risk of mucosa-associated lymphoid tissue (MALT) B-cell lymphoma in pSS, typically affecting the salivary glands. On account of abnormalities in the B-cell system in pSS there is current interest in the use of anti-B-cell directed monoclonal antibodies to treat pSS and a number of clinical trials are in progress. This approach is already successfully in use for treating MALT lymphoma in pSS.