bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Does Imaging Add to the Management of Alzheimer's Disease?
Authors: Small Gary W. 
Published: August 2016

AbstractThe prevalence of Alzheimer's disease (AD) and dementia continues to rise. However, a significant number of patients are undiagnosed or untreated. Given the complexities of detecting cognitive impairment and the early signs of AD, this review discusses how advances in brain imaging can help assist in improving overall management. Imaging techniques and surrogate markers may provide unique opportunities to diagnose accurately AD in presymptomatic stages with practical consequences for patients, caregivers, and physicians. The possible outcomes for using imaging and surrogate markers as adjuncts to clinical examination and as screening tools for AD, as well as tangible and intangible advantages to early diagnosis and treatment, will be discussed. The specific value of using advanced serial imaging in patients with a genetic disposition to AD will be evaluated. If neurons can be protected from neurodegenerative damage in early stages, this may preserve patient cognition, function, and quality of life, and may confer considerable societal healthcare benefits.
Quality of Life in Obsessive-Compulsive Disorder
Authors: Stein Dan J. , Allen Andrea , Bobes Julio , Eisen Jane L. , Figuera M. L. , Iikura Yasuro , Koran Lorrin M. , Hollander Eric 
Published: August 2016

AbstractThe construct of quality of life (QOL), which has both subjective and objective components, has gained increasing importance in psychiatric research for several important reasons, not the least being the current importance of pharmacoeconomic issues. Obsessive-compulsive disorder (OCD) has been suggested to be the worlds 10th most disabling disorder, and pharmacoeconomic studies have indicated that its cost to the world economy runs into the billions of dollars. The use of QOL scales derived from general medicine and other areas of psychiatry has demonstrated the enormous negative impact of OCD on several domains, including occupational function, social function, and family function. Further work to ascertain the extent of changes in QOL during treatment of OCD is necessary.
Clinical Considerations in Selecting and Using Atypical Antipsychotics
Authors: Newcomer John W. 
Published: August 2016

AbstractPatients with schizophrenia have a 20% shorter lifespan than people without the disorder. An increased risk of cardiovascular morbidity and mortality is also associated with schizophrenia. Atypical antipsychotics may contribute to the prevalence of cardiovascular disease by causing weight gain and increased adiposity, risk of insulin resistance, hyperglycemia, diabetes, and hyperlipidemia. Atypical antipsychotics that produce the greatest degree of weight gain also appear to impose the greatest risk of diabetes and hyperlipidemia. Recent evidence suggests that atypical antipsychotics may even affect glucose and lipid metabolism independent of weight gain. Among the currently marketed antipsychotics, clozapine and olanzapine appear to produce the greatest degree of weight gain. Moderate increases in weight are also observed with quetiapine and risperidone. Only ziprasidone and aripiprazole appear to be weight neutral. Atypical antipsychotics that produce the greatest degree of weight gain also appear to carry the greatest risk of diabetes and hyperlipidemia. Because of the potential for atypical antipsychotics to cause weight gain and adversely affect glucose and lipid metabolism, clinical monitoring of these parameters is critical. Dietary modification and exercise may be critical to addressing antipsychotic-induced weight gain and its consequences. In patients with persistent weight gain, evaluation of the risks and benefits of ongoing medications and consideration of switching to an antipsychotic with lower weight-gain liability may improve health outcomes.
A Prospective Pilot Study of Levetiracetam for Body Dysmorphic Disorder
Authors: Phillips Katharine A. , Menard William 
Published: August 2016

ABSTRACTIntroduction:Body dysmorphic disorder (BDD) is an often severe disorder, but few treatment studies have been conducted.Objective:This pilot study explored the efficacy and safety of the antiepileptic medication levetiracetam for BDD.Methods:Seventeen subjects withDiagnostic and Statistical Manual of Mental Disorders, Fourth EditionBDD participated in a 12-week open-label levetiracetam trial. Subjects were assessed at regular intervals with standard measures.Results:In intent-to-treat analyses, scores on the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS), the primary outcome measure, decreased from 32.5±4.7 at baseline to 21.5±11.0 at endpoint (P<.001). Approximately 60% (n=9) of subjects were responders (≥30% decrease on the BDD-YBOCS). The mean time to response was 4.6±2.8 (range: 2-10) weeks. Scores also significantly improved on the Brown Assessment of Beliefs Scale, the Hamilton Rating Scale for Depression, the Global Assessment of Functioning Scale, and the Social and Occupational Functioning Assessment Scale. Scores did not significantly improve on the Quality of Life Enjoyment and Satisfaction Questionnaire, the Beck Anxiety Inventory, or the Social Phobia Inventory. The mean endpoint dose of levetiracetam was 2,044.1±1,065.2 (range: 250–3,000) mg/day, and it was relatively well-tolerated.Conclusion:Randomized, double-blind placebo-controlled studies of levetiracetam for BDD are needed to confirm these preliminary findings.
The Pathogenesis of Alzheimer's Disease and the Role of Aβ42
Authors: Golde Todd E. 
Published: August 2016

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β-amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.
Early Identification and Treatment of Schizophrenia
Authors: Perkins Diana O. 
Published: August 2016

AbstractSchizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia.In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.
Introduction-The Brain as a Substrate for Psychotropic Therapeutics
Authors: Keck Paul E. 
Published: August 2016

AbstractBipolar disorder is a prevalent psychiatric disorder with a high rate of misdiagnosis and evidence of degenerative progression. Research indicates that the interval between bipolar episodes decreases steadily until the patient settles into a relatively frequent course of mania and depression. Various imaging techniques have been used in the understanding of the brain pathology underlying bipolar disorder through identification of patterns consistent with disruption of the normal brain activity in bipolar patients. These techniques have demonstrated evidence of abnormalities in the structure and function of the prefrontal cortex. In addition, the cerebellar vermis, which serves as an error-detection function to modulate the iterative network, appears to shrink with recurrent episodes. Functional imaging demonstrates that the anterior limbic network is overactivated and overresponsive in patients with bipolar disorder. In many patients, those deficits are often compensated for by activation of other brain areas. Ultimately, when the compensation fails, expression of bipolar symptoms arise. Using magnetic resonance spectroscopy, simple models can be constructed based on the hypothesis that mitochondrial function may be impaired in bipolar disorder. There is also increasing evidence that psychotropic medications can affect specific brain regions that are thought to be involved in the pathogenesis of psychiatric disorders. Glutamate levels appear to be elevated in untreated patients with bipolar disorder, which may cause glutamatergic neurotoxicity and negative therapeutic implications. Further advances in brain imaging may contribute to the improvement of available therapies and the understanding which treatments will be most suitable for specific patients.
The Complexity of ADHD: Diagnosis and Treatment of the Adult Patient With Comorbidities
Authors: Newcorn Jeffrey H. , Weiss Margaret , Stein Mark A. 
Published: August 2016

AbstractAttention-deficit/hyperactivity disorder (ADHD) is an impairing but usually treatable condition. Popular culture propagates the myth that ADHD recedes with age; this is not the case. Although it is common, <20% of adults with ADHD are diagnosed or treated. Adults with ADHD show significant comorbidities with depressive disorders, anxiety disorders, substance use, oppositional defiant disorder, personality disorders, sleep problems, and learning disabilities. However, symptoms that result from ADHD, such as mood symptoms or lability, are often mistaken for comorbid disorders. Comorbidity with ADHD impacts treatment compliance, treatment response, and patient insight. Insufficient data on the interaction between ADHD and comorbidities impedes proper diagnosis and treatment. Better clinical tools for assessing these conditions are needed. Food and Drug Administration-approved pharmacologic treatments for adult ADHD include stimulants, dexmethylphenidate, and the nonstimulant atomoxetine. Effect sizes of approved medicines at approved doses are half those seen in children. Adults may also need longer duration of medication effects than children. Short-acting stimulants are likely to result in poorer adherence and have a higher risk for diversion or abuse. Risk of abuse is a major concern; stimulant treatments are controlled substances, and children with ADHD show increased risk of substance abuse. Psychosocial interventions may be beneficial in treating both ADHD and comorbidities.In this expert roundtable supplement, Margaret Weiss, MD, PhD, presents a comprehensive overview of complications surrounding differential diagnosis in adults with ADHD. Next, Mark A. Stein, PhD, reviews evaluation, comorbidity, and development of a treatment plan in this population. Finally, Jeffrey H. Newcorn, MD, provides a discussion on the pharmacologic options available for adults with ADHD, considering dosages specific to adults and common comorbidities.
Pharmacoepidemiology: Examples of Databases and Studies
Authors: Wang Philip 
Published: August 2016

AbstractPharmacoepidemiology, the study of the effects of drugs in large numbers of people, is a relatively new discipline that applies the methods of epidemiology to clinical pharmacology. Premarketing clinical trials remain the only way to scientifically determine whether a drug is causally effective, yet these trials do not provide information that allows for estimates about rare, late, or off-label toxicities associated with the drug in question. Increasing concern about common and debilitating adverse effects of medications has highlighted the need for enhanced postmarketing surveillance to follow up on clinical trials. There is a further concern regarding the broader issue of the risk-benefit ratio of certain medications. Computerized databases are a good source of information on which to lay the foundations of postmarketing research. A system of cross-linked computerized medical records may better enable researchers and physicians to realistically monitor postmarketing safety and incorporate monitoring benefits. The same research could also elucidate the net public health effect of regulatory decisions. The Veterans Affairs database in the United States and PHARMO in the Netherlands may represent good models on which to base future postmarketing surveillance studies.In this expert roundtable supplement, Brian L. Strom, MD, provides an overview of the appropriate use of large computer databases in pharmacoepidemiology studies. Philip Wang, MD, DrPH, discusses the advantages of pharmacoepidemiologic studies over clinical trials in correctly detecting drug safety issues. Francesca Cunningham, PharmD, reviews a large computer database that is currently in use within the VA healthcare system, and Ron M.C. Herings, PharmD, PhD, discusses the development of the PHARMO system in the Netherlands
Veterans Affairs Databases
Authors: Cunningham Francesca 
Published: August 2016

AbstractPharmacoepidemiology, the study of the effects of drugs in large numbers of people, is a relatively new discipline that applies the methods of epidemiology to clinical pharmacology. Premarketing clinical trials remain the only way to scientifically determine whether a drug is causally effective, yet these trials do not provide information that allows for estimates about rare, late, or off-label toxicities associated with the drug in question. Increasing concern about common and debilitating adverse effects of medications has highlighted the need for enhanced postmarketing surveillance to follow up on clinical trials. There is a further concern regarding the broader issue of the risk-benefit ratio of certain medications. Computerized databases are a good source of information on which to lay the foundations of postmarketing research. A system of cross-linked computerized medical records may better enable researchers and physicians to realistically monitor postmarketing safety and incorporate monitoring benefits. The same research could also elucidate the net public health effect of regulatory decisions. The Veterans Affairs database in the United States and PHARMO in the Netherlands may represent good models on which to base future postmarketing surveillance studies.In this expert roundtable supplement, Brian L. Strom, MD, provides an overview of the appropriate use of large computer databases in pharmacoepidemiology studies. Philip Wang, MD, DrPH, discusses the advantages of pharmacoepidemiologic studies over clinical trials in correctly detecting drug safety issues. Francesca Cunningham, PharmD, reviews a large computer database that is currently in use within the VA healthcare system, and Ron M.C. Herings, PharmD, PhD, discusses the development of the PHARMO system in the Netherlands.
Managing the Acutely Agitated and Psychotic Patient
Authors: Nordstrom Kimberly , Allen Michael H. 
Published: August 2016

AbstractAgitation can present as an emergency in the course of numerous psychiatric conditions including intoxication, schizophrenia, bipolar disorder, and delirium. This article reviews relevant literature regarding the definition, etiology, measurement, and management of episodic agitation and pays particular attention to intramuscular treatments. The impact of changes in methodology between the era of first- and second-generation antipsychotics, the implications of those changes for external validity of studies of second-generation studies, and the recent evolution of expert consensus are discussed.
Panic Disorder: Broadening Conceptualizations and Improving Treatment
Authors: Pollack Mark H. 
Published: August 2016

Attempts to understand the underlying etiology of panic disorder have, at times, oscillated between reductionistic biologic or psychologic characterizations that have put pharmacotherapists and cognitive-behavioral therapists on opposite sides of a fence with patients caught in the middle. However, research emerging over the last couple of decades is pointing to a more complex interplay between dysregulated neurobiological systems and psychological factors that influence the manifestations of fear and anxiety and permit a more nuanced view of the etiology of panic disorder while pointing to potential rational strategies for treating patients. The articles in this supplement explore a range of explanatory models relevant to the underlying etiology of panic disorder, and then focus on treatment, including pharmacologic agents, and a paradigm in which cognitive-behavioral therapy (CBT) can be efficiently and effectively integrated with pharmacotherapy in an attempt to optimize patient care.In the first article, David Baldwin, MB, BS, DM, FRCPsych, discusses the burden of panic disorder to patients and society; the difficulties associated with misdiagnosis and inadequate treatment; the challenges imposed by excess healthcare utilization, reduced quality of life, and psychiatric and medical comorbidity; and the implications for therapeutics.
Easing the Burden of Panic Disorder: Comorbidity, Diagnosis, and Implications for Treatment
Authors: Baldwin David 
Published: August 2016

AbstractPanic disorder (PD) is typically a distressing, chronic, and recurrent mental disorder associated with a high rate of comorbidity with other mood, anxiety, and substance abuse disorders, increased risk of medical morbidity and mortality, and marked impairment of functioning and reduced quality of life. Most patients with PD first seek treatment in emergency room or general practice settings. In the overwhelming majority of cases, PD patients present with primarily somatic symptoms, many of which are common to medical illnesses. It is, therefore, not surprising that PD is often misdiagnosed and that patients with this disorder often spend years seeking treatment and undergoing costly and unnecessary tests and medical consultations before receiving a correct diagnosis. Better diagnosis and treatment of PD to achieve remission and prevent relapse has the potential to reduce the burden of this illness to the individual and society.
Metabolic Differences of Antipsychotics Among the Races
Authors: Henderson David C. 
Published: August 2016

AbstractAs the United States population continues to grow and diversify, physicians must be equipped to treat patients of different races and ethnicities. Current data suggest that certain ethnic minority groups may be predisposed to a variety of clinical conditions, including obesity, diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease. Furthermore, as physicians begin to turn more frequently to atypical antipsychotics in psychiatric illness, they face a growing concern regarding the development of metabolic side effects, especially in a US population that is gradually becoming more obese from a demographic standpoint. In addition, certain ethnic groups may be more susceptible to these metabolic effects. The metabolic side effects induced by the atypical antipsychotics vary greatly, with the newer agents generally displaying fewer and less severe side effects, indicating that the particular agent chosen is of critical importance. A risk/benefit assessment, taking into consideration any genetic predisposition, preexisting risk factors, and the side-effect profile of the specific agent, is paramount to the successful management of these patients. The ultimate goal is careful consideration of possible metabolic side effects in patients taking atypical antipsychotics, in order to avoid serious consequences.
Avoiding Side Effects in Ethnically Diverse Patients
Authors: Nasrallah Henry A. 
Published: August 2016

AbstractOptimal treatment for patients with mental health illness depends upon accurate diagnosis, individualized treatment, patient adherence to effective agents, and an intact family support system. Healthcare system (eg, limited access to certain medications), provider (eg, bias and discrimination), and patient factors (eg, biologic and cultural) greatly influence the level of mental health care given, especially to minority populations. Furthermore, limited data in African Americans, Hispanics, and Asians suggest that there are racial, ethnic, and cultural variations in responsiveness to antipsychotic medications, as well as potential differences in the types, rates, and severity of adverse events. Non-Caucasian patients tend to receive older, less-expensive agents, sometimes at higher doses (African Americans, leading to potentially intolerable side effects and early withdrawal of therapy or a less than optimal therapeutic response, respectively. Differences in response may have a biologic, pharmacokinetic, or pharmacodynamic basis and may also be influenced by lifestyle factors (eg, diet, smoking). Variations in dopamine receptor occupancy and cytochrome P450 polymorphism may explain some racial/ethnic differences in antipsychotic effects and adverse-event profiles, suggesting that dosing may need to be individualized based on ethnicity. The newer atypical antipsychotics, while seemingly better tolerated compared with conventional antipsychotics, may not be totally devoid of bothersome side effects (eg, extrapyramidal side effects) in minorities. While further research is needed, recognition of potential interracial/ethnic pharmacogenetic differences may help minimize intolerable side effects and achieve optimal psychosis management.