bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 50-Year-Old Male with Cirrhosis, HCV, Alcohol-Use Disorder, and Unexpected Decline While on DAA Therapy
Authors: Michel Ng , Patel Alkesh N. , Martel-Laferriere Valerie , Perumalswami Ponni 
Published: August 2014

CME Educational Objectives

1.
Review concepts in the terminology, diagnosis, treatment, and prognosis of hepatitis C in the setting of alcohol-use disorder.

2.
Understand interactions between telaprevir, a US Food and Drug Administration–approved direct-acting antiviral for the treatment of hepatitis C virus, and commonly used psychotropic medications.

3.
Provide strategies for managing hepatitis C virus–infected patients with concurrent alcohol-use disorder.

The patient is a 50-year-old white man with a history of chronic hepatitis C virus (HCV) genotype 1b, depression, anxiety, hypertension, and alcohol-use disorder. His HCV infection was acquired 30 years ago. He has been followed at the liver medicine practice at Mount Sinai Hospital for the past 5 years. Despite recommendations from his hepatology team to abstain from alcohol and initiate a trial of treatment for HCV, the patient chose to defer currently available treatments, having heard of promising news about interferon-sparing regimens to be released in the near future.
Neuronal Mechanisms of Placebo Effects
Authors: Nayak Devdutt , Patel Pankaj 
Published: August 2014

Placebo responses are complex and work through several neurobiological mechanisms. The neurotransmitters implicated thus far are dopamine (DA), gamma-aminobutyric acid (GABA), cholecystokinin (CCK), opioids, serotonin, and endocannabinoids. Both conscious expectations and unconscious conditioning can bring about molecular changes using the above neurotransmitters along the distributed biological systems, subserving cognition, emotions, pain control, reward, and learning.
Expectations can enhance DA secretion in the reward circuitry of the brain, which has a nucleus accumbens at its epicenter. The prefrontal cortex (PFC), which controls attention and emotional memories, negotiates the path to the reward. The nucleus accumbens (NAc), after capturing the sole attention of the PFC, is able to modulate arousal, emotional tone, and autonomic tone to make the brain seek reward of therapeutic benefit, even when no active treatment is offered. Both DA and endogenous opioids play a key role in modulation of placebo responsiveness. The negative expectations of the person regarding treatment or negative suggestions given by the treater can amplify anxiety and pain by activating several brain regions, such as the anterior cingulate cortex (ACC), PFC, and the insula. Thus, anticipatory anxiety generated acts on two independent pathways: the hypothalamic pituitary adrenal (HPA) axis and the CCKergic pro-nociceptive system.
By acting on anxiety, benzodiazepines can block both pathways and reduce pain. But CCK antagonists such as proglumide can only prevent nocebo hyperalgesia, and have no effect on HPA hyperactivity. The ebb and the flow of opioid/CCKergic systems produce the opposing effects of placebo/nocebo. The activation/deactivation between endogenous opioids/DA in NAc helps us understand both placebo and nocebo responses. There are parallels between the placebo response and classical conditioning. Endocrine, immune, and autonomic responses can be conditioned by placebos. Both the expectancy and conditioning mechanisms mediate placebo responses contingent upon previous experiences and social observational learning.
Use of Placebos Poses Ethical Dilemma
Authors: Nayak Devdutt , Chodha Vicky 
Published: August 2014

The term “placebo” lives in infamy in the history of medicine and medical research because of its association with fraud, fakery, coercion, and abuse and has promulgated progressively stricter regulations and guidelines. Opposition to using placebo control in clinical trials is based on the principles of biomedical ethics: beneficence, non-maleficence, justice, and autonomy. Many psychiatric disorders affect thinking, ability to reason, and judgment to act in one’s best interests, and many patient volunteers are not aware that their participation does not ensure getting the desired treatment.The Declaration of Helsinki requires that every patient in a clinical trial receive the best-proven diagnostic and therapeutic method for the condition under study — a concept that just about rules out using placebo control in clinical and investigational drug research.The U.S. Food and Drug Administration does not require placebo control in randomized, controlled trials but points out non-superiority of active comparator trials in psychiatric disorders and suggests that placebos can be used when “risk of death or serious harm is not at stake,” as they are not in many psychiatric conditions.Many physicians fail to recognize the potential harm of using negative language in their clinical dialogue with patients. In everyday practice, the catch-22 inherent in information disclosure must be minimized. Too little information is antithetical to obtain informed consent and harms patient’s autonomy for decision-making. Too much information, especially about side effects, increases the possibility of nocebo effects and resulting nonadherence to treatment. “Positive framing” of information and tactfulness are the great allies of the physician.
Enhancing Placebo Effects in Clinical Care
Authors: Nayak Devdutt , Patel Pankaj 
Published: August 2014

Sound principles of clinical practice emphasize positive therapeutic relationships, good communication skills, and alleviation of pain and suffering. Psychiatrists use the healing power of both words and drugs. Unfortunately, many psychiatric drugs have failed to show a robust effectiveness in real-world practice and have only a marginal intra-class difference between psychotropics that often comes at the price of intolerable side effects. A significant part of the observed efficacy of many drug treatments is derived from non-specific treatment effects (ie, placebo response). Psychotherapy research suggests that all bona fide psychotherapies have equivalent efficacy, regardless of the claims of their specific technique touted by partisan practitioners. Jerome Frank asserted 50 years ago that there are “curative” features common to all psychotherapies, namely: a person in distress, an expert, a healing setting and a ritual, and explanation for the condition. Ego development psychology informs us that self-soothing is learned by an infant from a nurturing mother, and the healing power of this bond is later transferred to physicians as “culturally sanctioned parental figures.”
Placebo-enhancing practitioners tend to be sensitive, caring, empathic listeners; encourage the patient to participate in decision-making; adapt their goals to patients’ needs and values; optimistic and impart hope; and are perceived by their patients as warm, friendly, reliable, and trustworthy. Good psychiatrists validate their patients’ suffering, are advocates and “cheerleaders,” and strive to restore patients’ self-efficacy, decrease demoralization, and enhance coping skills.
Giving people the best effective treatment, along with positive expectations, realistic optimism, and hope, strengthens the healing relationship, maximizes the placebo effect, and increases patients’ chances of responding in the future.
Intimate Partner Violence and Military Women
Authors: Tinney Glenna 
Published: August 2014

Intimate partner violence (IPV) is a significant issue that affects all women, including those who serve in the military. The myriad of issues faced by active-duty women who experience IPV is very similar to those of women who have never been in the military. However, active-duty women have an additional layer of challenges and concerns related to the military culture and the military’s response to IPV. Many women in the military have experienced individual trauma, including IPV, at some point in their lives, be it before, during, and/or after leaving the military.
This article provides data from the first survey that have ever compared military and civilian rates of IPV, sexual violence, and stalking. It also addresses the context in which the violence is embedded, the impact on risk and danger, the consequences of a trauma history, and a trauma-informed approach for a screening, assessment, and intervention.
Diagnosis of Food Allergy
Authors: Bégin Philippe , Nadeau Kari C. 
Published: August 2014

CME Educational Objectives

1.
Discuss the pre-test clinical assessment of a patient with a suspected food allergy.

2.
Review the currently available diagnostic tests and their performance for frequent food allergens.

3.
Interpret allergy tests in light of the pre-test assessment to determine final probability of food allergy and indication for referral for food challenge.

Diagnosis of food allergy can be challenging. Given the limited specificity of available allergy tests, these need to be interpreted in light of pre-test probability that is determined by a careful history. Using likelihood ratios calculated from previous publication may allow a more individualized assessment. This approach is likely to be most useful in patients with low to moderate results, below the 95% positive predictive value for that food. This review covers the diagnostic approach of immunoglobulin E-mediated food allergy. We first focus on the pre-test clinical assessment of a patient with a suspected food allergy. We then compare currently available diagnostic tests and discuss their performance for frequent food allergens. Finally, we conclude with the interpretation of allergy tests in light of the pre-test assessment to determine final probability of food allergy and indications for referral to an allergy specialist for food challenge.
Vaccines in the Pipeline: The Path from Development to Use in the United States
Authors: Pickering Larry K. , Walton L. Reed 
Published: August 2014

CME Educational Objectives

1.
Review the current US Food and Drug Administration licensure process for vaccines.

2.
Describe the mechanism followed for developing ACIP recommendations.

3.
Summarize the potential for future vaccine development.

New vaccines in the United States go through a complex process on their path from development to the domestic market involving an intricate partnership of public and private agencies and organizations. This process includes licensure by the US Food and Drug Administration, the development of recommendations by the Advisory Committee on Immunization Practices, and safety oversight post-licensure. This article examines the roles of the US Food and Drug Administration and the Centers for Disease Control and Prevention as well as certain professional organizations in governing the testing, marketing, and usage of new vaccines. Vaccines currently in development to treat numerous infectious and noninfectious diseases are also examined and compared with frameworks of domestic vaccine development prioritization, past and present, as assessed by the Institute of Medicine.
Prevention and Control of Influenza and Dengue Through Vaccine Development
Authors: Greenberg David P. , Robertson Corwin A. , Gordon Daniel M. 
Published: August 2014

CME Educational Objectives

1.
Review the impact of influenza infection in the pediatric population.

2.
Discuss the importance of influenza B as a key cause of morbidity and review the progress on development and deployment of quadrivalent influenza vaccines.

3.
Articulate the epidemiology and impact of dengue worldwide and identify difficulties unique to developing a vaccine for this disease.

Influenza and dengue are viral illnesses of global public health importance, especially among children. Accordingly, these diseases have been the focus of efforts to improve their prevention and control. Influenza vaccination offers the best protection against clinical disease caused by strains contained within the specific year’s formulation. It is not uncommon for there to be a mismatch between vaccine strains and circulating strains, particularly with regards to the B lineages. For more than a decade, two distinct lineages of influenza B (Yamagata and Victoria) have co-circulated in the US with varying frequencies, but trivalent influenza vaccines contain only one B-lineage strain and do not offer adequate protection against the alternate B-lineage. Quadrivalent influenza vaccines (QIVs), containing two A strains (H1N1 and H3N2) and two B strains (one from each lineage) have been developed to help protect against the four strains predicted to be the most likely to be circulating. The QIV section of this article discusses epidemiology of pediatric influenza, importance of influenza B in children, potential benefits of QIV, and new quadrivalent vaccines.
In contrast to influenza, a vaccine against dengue is not yet available in spite of many decades of research and development. A global increase in reports of dengue fever (DF) and its more severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), suggest that US physicians will increasingly encounter patients with this disease. Similarities of the early signs and symptoms of influenza and dengue and the differences in disease management necessitates a better understanding of the epidemiology, clinical presentation, management, and prevention of DF by US physicians, including pediatricians. The article also provides a brief overview of dengue and discusses dengue vaccine development.
Prader-Willi Syndrome and Sleep-Disordered Breathing
Authors: Miller Jennifer , Wagner Mary 
Published: August 2014

CME Educational Objectives

1.
Identify commonly observed sleep abnormalities in patients with Prader-Willi Syndrome (PWS).

2.
Discuss the effects of growth-hormone therapy on sleep-disordered breathing in patients with PWS.

3.
Identify other sleep-related abnormalities encountered in patients with PWS.

Prader-Willi Syndrome is a complex neurogenetic disorder characterized by appetite dysregulation, obesity with decreased muscle mass and increased fat mass, behavioral problems, various endocrinopathies, and sleep and respiratory abnormalities. Respiratory issues include both central and obstructive sleep apnea, excessive daytime sleepiness, narcolepsy, and impaired ventilatory control. There is some controversy as to whether growth hormone treatment, which is the standard of care for patients with Prader-Willi Syndrome, exacerbates or ameliorates the sleep-disordered breathing issues associated with this syndrome. The natural history of sleep and breathing issues and the issues surrounding growth hormone treatment on sleep-disordered breathing are discussed.
Evaluation of Short Stature in Children
Authors: Ismail Heba , Ness Kathryn 
Published: August 2014

CME Educational Objectives

1.
Distinguish normal growth from pathological short stature.

2.
Identify key components in the history and physical exam in the evaluation of short stature.

3.
Outline the diagnostic evaluation, indications for growth hormone therapy and indications for referral to a specialist.

Normal growth in children is a reflection of general health and is the result of a complex interaction between genetic, nutritional, and hormonal factors. From conception through infancy, growth is mostly driven by maternal nutrition and the in utero environment. Genetic factors, growth and thyroid hormones, ghrelin, and sex steroids have a more prominent influence later. Normal growth is not linear; it is marked by periods of growth spurts, particularly during puberty, separated by periods of slow or immeasurable growth. There is often a period of growth deceleration observed before the onset of puberty, with maximal pubertal growth spurts occurring at Tanner stage III for girls and Tanner stage IV for boys. This is caused primarily by the combined effect of the increased amplitude of growth hormone pulses and sex steroids.
Short stature (SS), which is the subject of this review, is defined as a length or height more than 2 standard deviations below the mean for age and gender, which corresponds to a percentile below 2.5%. Taking a thorough patient history and completing a comprehensive physical examination are some of the most important diagnostic tools for pediatricians to use in the diagnosis of SS, and in making appropriate referrals as needed.
Musculoskeletal Screening: Developmental Dysplasia of the Hip
Authors: Roof Amanda C. , Jinguji Thomas M. , White Klane K. 
Published: August 2014

CME Educational Objectives

1.
Discover the proper techniques for identifying and diagnosing developmental dysplasia of the hip (DDH) on physical exam.

2.
Identify proper imaging modalities to use as an adjunct to the physical exam.

3.
Clearly delineate when a referral to a DDH specialist is necessary.

Developmental dysplasia of the hip (DDH) is common because it is present in 1 of 100 newborns. Failure to diagnose DDH and treat in infancy can result in significant long-term disability. Early diagnosis can be accomplished through a quick but careful physical examination of all newborns. Further selective screening by ultrasound is indicated for those children with risk factors for DDH, which include family history, breech presentation, and unstable hip examination at the initial newborn examination. Continued examination of the hip at all routine well-child checkups is mandatory through the first year of life because late presenting DDH may occur. Treatment with a Pavlik harness is not typically instituted in the neonate because many unstable hips stabilize without intervention, but it is indicated in children older than 2 weeks with hip instability. Ultrasound screening for infants with risk factors for DDH is recommended at age 6 weeks. Pavlik harness treatment for children with unstable hips or significant dysplasia on ultrasound is continued until the hips stabilize and show concentric reduction on imaging. With time, diagnosis and treatment evolve to accommodate the growing child. Infants who fail to respond to nonoperative management may require more extensive interventions. At any time when treatment is initiated, a DDH specialist should be involved in the patient’s care. If DDH is recognized early, treatment is less invasive, and long-term effects are minimized.
Initial Evaluation and Management of a First Seizure in Children
Authors: Chelse A.B. , Kelley Kent , Hageman Joseph R. , Koh Sookyong 
Published: August 2014

CME Educational Objectives

1.
Understand the initial evaluation of a child presenting with first seizure.

2.
Discuss the risk factors for seizure recurrence.

3.
Discuss the value of electroencephalography (EEG) and neuroimaging in diagnosis and treatment.

The pediatrician is often the first health professional notified of a child’s first seizure. First seizures cause much anxiety for parents and practitioners. Parents are frightened as they witness a paroxysmal event that involves convulsions or altered mental status, and as a result, they seek answers, reassurance, and support.
Every pediatrician faces the challenge of determining whether a child who had a paroxysmal event had a seizure. Therefore, it is important for the general pediatrician to have a good understanding of the diagnosis and management of a child’s first seizure. This review will discuss the definition of seizures and epilepsy, the critical questions to answer during the initial evaluation of a child’s first seizure, guidance for initial management, risk factors for seizure recurrence, and the value of electroencephalography in diagnosis and treatment.
Pediatric IBS: An Overview on Pathophysiology, Diagnosis and Treatment
Authors: Chogle Ashish , Mintjens Stijn , Saps Miguel 
Published: August 2014

Irritable bowel syndrome (IBS) is a common disorder in children and adults. The pathogenesis and pathophysiology of IBS remains incompletely understood. The biopsychosocial model, which conceptualizes chronic pain as a dysregulation of the gut-brain-homeostasis with peripheral and central factors mutually influencing each other, is the most accepted framework to explain IBS. Twin and family aggregation studies suggest a genetic component that does not exclusively explain the higher prevalence of IBS in certain families. Social learning (environmental factors) and maladaptive coping predispose children to develop IBS with greater disability and more frequent medical consultations. Early-life events constitute an additional risk factor for the development of IBS and other functional gastrointestinal disorders (FGIDs). Children with a history of cow’s milk protein hypersensitivity or abdominal surgeries have a higher prevalence of IBS and other FGIDs years later. IBS frequently follows an episode of acute gastrointestinal inflammation (infectious or non-infectious).
This article discusses the importance, known pathophysiological mechanisms, clinical approach, and evidence-based therapeutic options for the management of IBS in children and adolescents.
Multiplanar Osteotomies Guided by Navigation in Chondrosarcoma of the Knee
Authors: Aponte-Tinao Luis A. , Ritacco Lucas E. , Ayerza Miguel A. , Muscolo D. Luis , Farfalli Germán L. 
Published: August 2014

Surgical resection with adequate margins is the treatment of choice in chondrosarcoma. However, well-circumscribed lesions can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. This type of resection had been recently described in select patients with sarcomas; however, these osteotomies are technically demanding to plan and perform intraoperatively. The use of navigation to assist in surgery is becoming more frequently described in orthopedic oncology.
The authors performed multiplanar osteotomy resections guided by navigation and reconstruction with intercalary allografts in 5 patients with chondrosarcoma around the knee. All the patients were women, with a mean age of 56 years. Four tumors were located in the distal femur and 1 in the proximal tibia. The 5 surgical anatomic specimens were 3-dimensionally reconstructed postoperatively and superimposed on a preoperative plan to check whether the resected specimen was consistent with the preoperative planned resection. At final follow-up, no patient experienced a local recurrence or metastasis. Four osteotomies each were performed in 3 patients, and 3 osteotomies each were performed in 2 patients, so 18 planes were evaluated. Mean difference in distance between preoperative vs final planes was 2.43 mm. Average functional score was 29 points. All patients resumed activities of daily living without restriction. This study’s results show that navigation with adequate preoperative planning allows surgeons to intraoperatively reproduce the planned resection with accuracy in complex multiplanary resections.