bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Spectrum of Rapid Cycling
Authors: Suppes Trisha 
Published: August 2016

While rapid cycling was first identified by Dunner and Fieve in 1974, there is quite a good historical background on the concept. In the 1800s Falret and colleagues identified what they called a “circular course distinct from alternating.” What they meant by “alternating” was a period of remission following an episode. Currently, all types and ranges of cycling are lumped under one rubric; the spectrum ranges from having >4 cycling episodes, the minimum required for rapid cycling, through ultradian cycling, which is far more severe.While some patients manifest chronic depression with periodic hypermania, which is known as bipolar II, others have ultradian cycles, which are often seen as pure affective instability. We do not know whether these types represent different stages of a disorder that exists on a spectrum or whether they are actually distinct categories of the disorder: one being patients who experience mania, depression, and then remission; the second being those with more continuous cycling that includes ultradian cycling. Greater understanding of the biological underpinnings of the illness will help to determine whether these conditions exist on a spectrum.Rapid cycling may become less prevalent with age. In the Depression Collaborative Study, Coryell and colleagues found a diminishment of rapid cycling over the course of 13 years. Studies from the Stanley Bipolar Foundation group suggest that the cycling may accelerate in some, but not others. Over a long observation period in ~100 patients, Koukopoulos and colleagues found that once a pattern of rapid cycling is established in a patient, this pattern may become a hallmark of their illness.
Treatment-Refractory Epilepsy: An Evidence-Based Approach to Antiepileptic Monotherapy
Authors: Harden Cynthia L. , Ginsberg David L. , Kanner Andres M. , Bautista Jocelyn F. , Browne Thomas R. 
Published: August 2016

AbstractTreatment options for epilepsy have increased in the last decade with the introduction of several new antiepileptic drugs (AEDs). As drug selection becomes more challenging, the use of evidence-based guidelines to aid in treatment decisions has become increasingly valued. The American Academy of Neurology's (AAN) guidelines for the use of new AEDs in refractory epilepsy offers many benefits, including expert panel recommendations based on clinically relevant questions with evidence-based responses. However, lack of evidence from randomized-controlled trials, particularly as they relate to monotherapy, limits the recommendations and their use in practice. The studies of new AEDs as monotherapy in treatment-refractory epilepsy are difficult to incorporate into clinical use because they are driven by Food and Drug Administration requirements to show superiority over placebo or pseudoplacebo (ie, low dose of active drug) rather than by clinical questions. However, based on Class I evidence, the AAN guidelines have granted Level A recommendations (established effectiveness) for oxcarbazepine and topiramate monotherapy, and a Level B recommendation (probable effectiveness) for lamotrigine monotherapy in the use of refractory partial epilepsy. There is insufficient evidence to recommend gabapentin, levetiracetam, tiagabine, or zonisamide monotherapy. No monotherapy AED trials have been conducted in refractory generalized epilepsy. Because no differences in efficacy have been reported for AEDs as initial therapy of partial seizures, differences in adverse events, such as weight gain, tremor, and hair loss, are key in drug selection. More comparative studies between the AEDs are necessary for both monotherapy and add-on therapy for treatment-refractory epilepsy.
Interpreting the Efficacy Findings in the CATIE Study: What Clinicians Should Know
Authors: Meltzer Herbert Y. , Bobo William V. 
Published: August 2016

AbstractThe Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial was an effectiveness/”pragmatic” clinical trial designed to compare the efficacy, tolerability, and cost-effectiveness of four atypical antipsychotics (olanzapine, quetiapine, risperidone and ziprasidone) and a conventional antipsychotic (perphenazine) for an 18-month period in patients with schizophrenia. The study randomized 1,460 patients with fewer exclusion criteria than in most trials in hopes that this would allow for a more representative sample of outpatients in “real world” practice. Olanzapine demonstrated significant superiority in time to discontinuation for all cause and for lack of efficacy, as well as likelihood of hospitalization for relapse; however, it was associated with a significantly higher rate of metabolic side effects. Perphenazine exhibited comparable effectiveness with quetiapine, risperidone, and ziprasidone, and appeared to be as well tolerated as the atypicals. However, it had the highest rate of drop out due to extrapyramidal symptoms and was restricted to patients who did not have tardive dyskinesia (TD). This article examines the phase 1 CATIE results to guide the clinician in understanding how to interpret the findings, which were intended to be a guide for clinical practice. The nature of the patient population, the doses of drugs relative to one another, inclusion of patients who were treatment resistant, and exclusion of patients with TD from randomization to perphenazine were potential sources of bias in the study. In particular, the use of a higher-than-usual peak dose of olanzapine may have led to the superior results achieved with it. Practical suggestions are given for choice of antipsychotic medication in patients with chronic schizophrenia.
Sexual Dysfunction in Patients with Epilepsy: Communication Strategies and Assessment Tools
Authors: Fishman Olga , Ettinger Alan B. 
Published: August 2016

AbstractSexual dysfunction is common among patients with epilepsy, but many clinicians do not include inquiries about this aspect of the patient's health in their routine evaluations. This article presents approaches for taking a sexual history and for discussing sexual problems. The utility of standardized sexual dysfunction questionnaires is reviewed and the important elements of appropriate and effective counseling are highlighted.
Psychophysical and Neurochemical Abnormalities of Pain Processing in Fibromyalgia
Authors: Staud Roland , Spaeth Michael 
Published: August 2016

AbstractFibromyalgia pain is frequent in the general population, but its pathogenesis is only partially understood. Patients with fibromyalgia lack consistent tissue abnormalities but display features of hyperalgesia (increased sensitivity to painful stimuli) and allodynia (lowered pain threshold). Many recent fibromyalgia studies have demonstrated central nervous system (CNS) pain processing abnormalities, including abnormal temporal summation of pain. In the CNS, persistent nociceptive input from peripheral tissues can lead to neuroplastic changes resulting in central sensitization and pain. This mechanism appears to represent a hallmark of fibromyalgia and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established, only minimal peripheral input is required for the maintenance of the chronic pain state. Additional factors, including pain-related negative affect and poor sleep have been shown to significantly contribute to clinical fibromyalgia pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of fibromyalgia and other chronic pain syndromes.
Fibromyalgia Syndrome: Approach to Management
Authors: Russell I. Jon 
Published: August 2016

AbstractThe management of fibromyalgia syndrome (FMS) has traditionally been multimodal and multidisciplinary, including education, physical modalities, and medication. In this article, an acronym is offered to help the clinician remember the important components of management. An improved understanding of the pathogenesis of FMS has allowed substantial refinements in its treatment. This is particularly true for medications that target specific symptom domains, allowing individualization of therapy. Since all FMS patients experience pain, there has been emphasis on that domain although medications are now available to address two or more domains with monotherapy. In addition, a logical basis is provided to help the clinician design strategic polypharmacy.
Obsessive-Compulsive Disorder Spectrum as a Scientific “Metaphor”
Authors: Pallanti Stefano , Hollander Eric 
Published: August 2016

AbstractAs a result of clinical, epidemiological, neuroimaging, and therapy studies that took place in the late 1980s, obsessive-compulsive disorder (OCD) has been well-characterized in the field of anxiety disorders. Other disorders attracted attention for their similarities to OCD, and were located in the orbit of the disorder. OCD has become known as the “primary domain” of a scientific “metaphor” comprising the putative cluster of OCD-related disorders (OCRDs). It is a “paradigm” with which to explore basal ganglia dysfunction. The OCRDs share common phenomenology, comorbidities, lifetime course, demographics, possible genetics, and frontostriatal dysfunction (particularly caudate hyperactivity.) The adoption of this metaphor analogy has proven useful. However, 15 years since its emergence, the spectrum of obsessive-compulsive disorders remains controversial. Questions under debate include whether OCD is a unitary or split condition, whether it is an anxiety disorder, and whether there exists only one spectrum or several possible spectrums. Further work is needed to clarify obsessive-compulsive symptoms, subtypes, and endophenotypes. There is need to integrate existing databases, better define associated symptom domains, and create a more comprehensive endophenotyping protocol for OCRDs. There is also a need to integrate biological and psychological perspectives, concepts, and data to drive this evolution. By increasing research in this field, the OCD spectrum may evolve from a fragmented level of conceptualization as a “metaphor” to one that is more comprehensive and structured.
Psychobiology of Anxiety Disorders and Obsessive-Compulsive Spectrum Disorders
Authors: Stein Dan J. 
Published: August 2016

AbstractObsessive-compulsive disorder is currently classified as an anxiety disorder. However, there is growing interest in the concept of an obsessive-compulsive spectrum of disorders (OCSDs). The relationship between anxiety disorders and OCSDs has been questioned. The psychobiology of anxiety disorders and OCSDs is briefly reviewed in this article. While there appear to be several distinct contrasts in the underlying psychobiology of these conditions, there is also evidence of overlapping mechanisms. In addition, there are crucial gaps in our current database, confounding nosological decision-making. Conceptualizing various anxiety disorders and putative OCSDs as lying within a broader spectrum of emotional disorders may be useful. However, clinicians must also recognize that individual anxiety and obsessive-compulsive spectrum conditions, including disorders characterized by body-focused repetitive behaviors, have distinct psychobiological underpinnings and require different treatment approaches.
Subclinical Obsessive-Compulsive Disorder in Children and Adolescents: Additional Results From a “High-Risk” Study
Authors: Black Donald W. , Gaffney Gary R. 
Published: August 2016

AbstractIntroduction: The concept of subclinical obsessive-compulsive disorder is explored using data from a “high-risk” study of offspring of persons with (OCD) and offspring of controls. Offspring with OCD were compared to those with subclinical OCD, and those without either condition. Subclinical OCD is defined as the presence of obsessions and/or compulsions without functional impairment.Methods: Adults with OCD and their offspring 7–18 years of age were recruited through a tertiary care center psychiatric outpatient clinic, while controls (and their children) were recruited via advertisement. Parents and offspring were assessed using structured interviews and validated questionnaires at baseline and follow-up interviews.Results: Offspring from both proband groups were pooled to create three subject groups: group 1, offspring with neither condition (n=43); group 2, offspring with subclinical OCD (n=24); and group 3, offspring with full OCD (n=11). Offspring with subclinical OCD held the middle ground for most comparisons. They were more symptomatic than offspring without either condition (group 1), but less symptomatic than subjects with OCD (group 3). Across the board, comparisons of diagnoses, Child Behavior Checklist (CBCL) results; Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey results; and Leyton Obsessional Inventory (LOI) results were associated with subject group at baseline and follow-up. In post-hoc comparisons, subjects with subclinical OCD had fewer comorbid anxiety disorders and lower CBCL internalizing scale scores at follow-up. Parents of children with OCD had higher LOI symptom and severity scores than parents in those of groups 1 or 2.Conclusion: The findings suggest that subclinical OCD holds the middle ground between full-blown OCD and having neither condition in terms of obsessive-compulsive symptoms and severity, tics, associated mood/anxiety disorders, and general functioning. At least in persons at risk for OCD, the presence of subclinical OCD may herald the onset of OCD, though in others may be an independent condition that does not lead to full OCD.
Computerized Neuropsychological Assessments
Authors: Woo Ellen 
Published: August 2016

Computer-based measures to evaluate cognition have been used with growing frequency in recent years. These batteries are shown to be useful for identifying mild cognitive impairment (MCI) and dementia. There are few requirements to administer these tests. All that is typically needed is a computer, a response pad for patients to input their answers, and an examiner. In many cases, the examiner does not need to be a trained neuropsychologist. These computer-based assessments should yield a score report detailing the patient’s cognitive profile.An important advantage of computerized assessments over standard paper-and-pencil testing is that they can provide precise measurement at the millisecond level. This can be a more sensitive measure of cognitive impairment, especially in high-functioning older adults and in patients with milder levels of cognitive deficit. Computer tests also have a shorter assessment time. Many batteries take <1 hour to administer, whereas many standard neuropsychological batteries require >4 hours to complete. The presentation of items in some batteries can be adapted to patients’ performance levels to avoid floor effects (the test restricts how low a patients’ scores can be) and ceiling effects (the test restricts how high scores can be). Computer tests have increased standardization; they are administered the same way every time. Scoring is automatic, meaning the results are available immediately and human scoring error is reduced. Examiner effects are reduced, which is an important advantage because clinicians may differ in how they administer standard tests, which may impact patients’ responses. In addition, the batteries are easily transported, and multiple tasks can be made available on a single computer.
Cerebrospinal Fluid: When Is It Worthwhile to Do a Lumbar Puncture?
Authors: Peskind Elaine R. 
Published: August 2016

Clinicians should have an understanding of a lumbar puncture is indicated in the differential diagnosis of dementia and delirium. In most cases, this procedure is not commonly performed in outpatient practice for the differential diagnosis of dementia. However, in patients who have acute or subacute onset or a very rapid decline—such as in suspected Creutzfeldt-Jakob disease (CJD)—cerebrospinal fluid (CSF) 14-3-3, and tau proteins can be diagnostic for at least sporadic CJD. Practice parameters from the American Academy of Neurology (AAN) suggest performing a spinal tap on patients ≤55 years of age. However, that recommendation may not always be beneficial, particularly in a patient who has a prominent family history of either Alzheimer’s disease (AD) or frontotemporal dementia. Per the AAN practice parameter, lumbar puncture for CSF analysis is indicated in the diagnosis of central nervous system (CNS) infection, carcinomatous meningitis, or CNS vasculitis.Beyond the clinically indicated lumbar puncture, there is utility of CSF biomarkers, including CSF Aβ42, total tau, and phospho-tau, which are the best studied. These biomarkers may be useful for cases involving atypical presentations of dementia, eg, when it is difficult to determine if the patient has AD versus frontotemporal dementia. They may be most useful for cases in which there is an atypical presentation of the fluorodeoxyglucose PET image or PET image features of both AD and frontotemporal dementia.
Beyond Standard Anti-Dementia Therapies: Diet, Exercise, Socialization, and Supplements
Authors: Small Gary W. 
Published: August 2016

Several lines of evidence point to lifestyle choices that may improve brain health. Genetic factors are important to the process of aging, especially as it relates to vulnerability to Alzheimer’s disease (AD), but non-genetic factors clearly have a role as well. This paper highlights studies suggesting that diet, exercise, socialization, and supplements may protect the brain from age-related decline.Observational evidence has indicated that several dietary practices can help maintain the health of one’s brain. The first such practice is to moderate one’s caloric intake. Illnesses related to obesity, such as diabetes, hypertension, and high cholesterol, are associated with poorer brain health. The second is to increase one’s intake of antioxidant foods, such as fresh fruits, and vegetables. The third is to increase intake of foods rich in omega-3 fatty acids, such as fish and olive oil. These fats in the diet may be associated with lower risk of dementia. Finally, consuming low glycemic-index carbohydrates instead of high glycemic-index carbohydrates, which spike blood sugar levels and are associated with higher risk of type 2 diabetes, may benefit the brain.Many studies have been conducted on the connection between a lower risk for AD and healthy diet. While there are not much data from randomized-controlled trials, epidemiologic studies support the theory that diet can have an impact on vulnerability to AD.
Non-Amyloid Approaches to Neuroprotection
Authors: Sano Mary 
Published: August 2016

The introduction of the amyloid hypothesis, which identifies amyloid as the primary target for treating Alzheimer’s disease (AD), was a watershed in the field of AD research. Treatment approaches have since focused on how amyloid might be manipulated. In fact, there are challenges to amyloid manipulation. First, removal of amyloid has shown minimal clinical effects. Second, some data indicate that secretase modulation shows hints of stimulating feedback systems, which cause concern over how to effectively manipulate amyloid. Third, side-effect profiles of the direct manipulation of amyloid are not currently optimal. Finally, evidence suggests that cell and synapse loss may be better markers of dementia and its severity. Alternative approaches to direct manipulation of amyloid include antioxidant mechanisms for prevention, anti-inflammatory mechanisms for neuroprotection, manipulation of metabolic risks, modification of tau accumulation, and neuroregeneration.These alternative mechanisms of action provide support for a wide range of potential agents for clinical trials. The exact connection between mechanism of action and clinical outcomes is not well defined, but typically trial designs using these mechanisms attempt to measure affects on disease progression, often with longer studies that include established clinical outcomes accompanied by putative biomarkers of disease. One trend that has provided much information has been to examine the effects of these drugs in subjects at risk for AD, thereby expanding the intervention to prevention of disease. These studies include both secondary prevention studies, for example deferring onset in those with prodromal disease such as mild cognitive impairment (MCI), and primary prevention directed at those with no specific signs or symptoms.
Resilience and Anxiety
Authors: Davidson Jonathan R. T. 
Published: August 2016

While resilience has been overlooked in the therapeutics area, it has been well-documented in the literature. Since at least the 1970s, there has been an extensive literature published on child resilience including the longitudinal follow up studies of children from the Hawaiian island of Kawaii.The Anxiety and Traumatic Stress Program at Duke University Medical Center in Durham, North Carolina, became interested in resiliency as a slightly serendipitous observation during the course of a trial studying fluoxetine and placebo in people with PTSD. A measure evaluating how upset a person had been in the last week by life stresses, showed that fluoxetine was very effective in helping people cope with daily stresses (Slide 13).The simple definition of resilience is the ability to bounce back from adversity. However, the literature cites a number of other aspects to resilience (Slide 14). Kobasa, a psychologist who has worked extensively in the area of resilience, tends to see it as similar to hardiness, in which there are certain components that are very salient. The first component is the view of stress, or difficulty, as a challenge. Second, is to have a sustained commitment to overcome whatever is necessary. Third, is the ability to possess internal control while being able to accept things one does not have complete control over.The importance of having support from other people has been emphasized by Rutter. He theorized that one has the capacity to have close and secure attachments and a good sense of self-efficacy. He also notes the strengthening effects of stress. In children who cope well with difficulties, it is useful to tap into previous successes in order to harness some confidence from prior success. An action-oriented approach to problems, called active coping, can be useful.