bluuebunny/crossref_metadata_2025 huggingface dataset:
The limping child
Authors: Kimura Yukiko , Southwood Taunton R.
Published: February 2018

This chapter presents a systematic approach to evaluating the limping child, beginning with a careful history, then the physical examination, and proceeding to the musculoskeletal examination followed by targeted investigations. Tables with useful tips for differential diagnosis based on age and laboratory testing, as well as diagnostic algorithms, are presented.
Respiratory system
Authors: Hoyles Rachel K. , Wells Athol U.
Published: February 2018

Pulmonary involvement is common in the connective tissue diseases (CTDs) and is associated with significant morbidity and mortality. Improved management of systemic disease has led to increasing numbers of surviving patients with clinically significant pulmonary disease. Screening for pulmonary complications highlights the frequency of subclinical involvement. In this chapter, the pulmonary manifestations of the more common CTDs are detailed, including rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), Sjögren’s syndrome (SS), and, more briefly, ankylosing spondylitis (AS). A broad spectrum of pulmonary disorders are seen in association with the CTDs or the drugs used to treat the underlying disorder, including interstitial lung disease, pulmonary infections, airways disease, pulmonary nodules, pleural disease, chest wall pathology and pulmonary vascular disease; the discussion is stratified by pulmonary complication. In many cases, two or more pulmonary manifestations of CTD coexist or there are other concurrent diseases such as asthma and lung cancer, resulting in potentially confusing mixed imaging and pulmonary function abnormalities. This chapter presents a comprehensive approach to the investigation, screening, prognostic evaluation, and treatment decisions in pulmonary disease associated with the CTDs.
Genetics of osteoarthritis
Authors: MacGregor Alex , Valdes Ana , Williams Frances M. K.
Published: February 2018

In this chapter we outline the approaches which have been adopted to identify genetic variants predisposing to osteoarthritis (OA), a condition long recognized as having a heritable component. Such routes to their identification include examining mendelian traits in which OA is a feature, candidate gene studies based on knowledge of OA pathobiology, linkage analysis in related individuals, and, more recently, genome-wide association studies in large samples of unrelated individuals. It is increasingly evident that the main symptom deriving from OA—notably joint pain—also has a genetic basis but this is differs from that underlying OA. Variants convincingly shown to predispose to OA lie in the GDF5 and MCF2L genes and in the chr7 cluster mapping to the COG5 gene, in addition to the ASPN gene in Asian populations. Those associated with pain in OA include TRPV1 and PACE4. Epigenetic influences are also being explored in both the pathogenesis of OA and the variation of pain processing.
Cellular side of acquired immunity (T cells)
Authors: Eljaafari Assia , Miossec Pierre
Published: February 2018

The adaptive T-cell response represents the most sophisticated component of the immune response. Foreign invaders are recognized first by cells of the innate immune system. This leads to a rapid and non-specific inflammatory response, followed by induction of the adaptive and specific immune response. Different adaptive responses can be promoted, depending on the predominant effector cells that are involved, which themselves depend on the microbial/antigen stimuli. As examples, Th1 cells contribute to cell-mediated immunity against intracellular pathogens, Th2 cells protect against parasites, and Th17 cells act against extracellular bacteria and fungi that are not cleared by Th1 and Th2 cells. Among the new subsets, Th22 cells protect against disruption of epithelial layers secondary to invading pathogens. Finally these effector subsets are regulated by regulatory T cells. These T helper subsets counteract each other to maintain the homeostasis of the immune system, but this balance can be easily disrupted, leading to chronic inflammation or autoimmune diseases. The challenge is to detect early changes in this balance, prior to its clinical expression. New molecular tools such as microarrays could be used to determine the predominant profile of the immune effector cells involved in a disease process. Such understanding should provide better therapeutic tools to counteract deregulated effector cells.
Antirheumatic drugs in pregnancy and lactation
Authors: Marshall Tarnya , Abdulkader Rita , Sharma Poonam
Published: February 2018

Antirheumatic drugs in pregnancy and lactation are increasingly a common clinical dilemma. With the shift towards early, aggressive control of autoimmune diseases and with the advent of newer therapeutic agents, there is a need to understand the effects of these medicines in pregnancy and lactation, on fertility in both men and women, and on the process of spermatogenesis, in order to understand the risk of teratogenesis.
Although there are some limited data available for the use of antirheumatic drugs in pregnancy and lactation, much of our knowledge is derived from animal models and from limited clinical experience in human pregnancy.
The balance of therapeutic benefits and risks of harm to mother and fetus should always be carefully considered: it may vary between individuals and should be assessed on a case by case basis. Because of these issues, pregnancy should always be discussed and planned in advance, in part to reduce disease activity prior to conception but also to minimize risk to the fetus.
In this chapter we use the available evidence to discuss medicines which are commonly used in the treatment of rheumatological autoimmune diseases, and cover disease-modifying antirheumatic drugs (DMARDS) and biological agents.
Rheumatoid arthritis—diagnosis
Authors: Aletaha Daniel , Radner Helga
Published: February 2018

Rheumatoid arthritis (RA) is among the most disabling form of chronic inflammatory joint disease. Not all forms of arthritis develop into RA; on the contrary, it may be very challenging to differentiate RA from cases of arthritis that are self-limiting or caused by another disease. Evaluation of early arthritis includes some basic steps, such as excluding trauma, crystal, or infectious-related disease, as well as considering additional features that may guide towards a specific diagnosis. If no specific diagnosis can then be made, the presentation can be labelled as undifferentiated arthritis. Typical differential diagnoses of RA include viral polyarthritis, seronegative spondylarthropathies, polymyalgia rheumatic, and other systemic rheumatic diseases.
In 2010, new classification criteria were published that led to a change in the approach to RA. Compared to the previous criteria, the American College of Rheumatology (ACR) 1987 criteria, a scoring system was devised, appreciating the type and number of affected joints (up to 5 points), as well as serology (up to 3 points), elevated acute-phase reactants (1 point), and a symptom persistence of 6 weeks or longer (1 point). If 6 or more points are reached, then classifiable RA is present. Importantly, classification status, which is used for study purposes, is not always identical to the diagnostic status, which often leads to clinical treatment.
Reactive arthritis and enteropathic arthropathy
Authors: Gaston J. S. Hill
Published: February 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.
Systemic lupus erythematosus—clinical features and aetiopathogenesis
Authors: Gordon Caroline
Published: February 2018

Systemic lupus erythematosus (SLE or lupus) is a multisystem, autoimmune disease associated with the formation of autoantibodies that form pathological immune complexes and activate a number of inflammatory pathways. The disease is characterized by remissions and relapses (flares) that can present with a variety of clinical manifestations. The symptoms and signs may range from mild features that can be treated easily to organ and even life threatening manifestations requiring potent immunosuppression. This chapter will review the epidemiology and pathology of lupus, then the clinical features including differential diagnosis and investigation of adult patients with SLE. Finally the classification, diagnosis, monitoring and outcome of lupus patients will be discussed.
Behçet’s syndrome
Authors: Yurdakul Sebahattin , Seyahi Emire , Yazici Hasan
Published: February 2018

Behçet’s syndrome is a systemic inflammatory panvasculitis (affecting all sizes of vessels) of unknown aetiology. It is in vogue to include it among the systemic autoinflammatory conditions. Behçet’s syndrome is more frequent along the ancient ’Silk Route’ across Asia than it is in Western countries. The usual onset is the second or third decade, equally affecting either gender. However, young patients and male patients have more severe disease. Almost all patients have recurrent oral ulceration. Scar-forming genital ulcers, a variety of skin lesions including acneiform, erythema nodosum-like lesions, arthritis, potentially blinding panuveitis, thrombophlebitis, gastrointestinal disease, central nervous system (CNS) involvement, and life-threatening bleeding pulmonary artery aneurysms are seen. The pathergy phenomenon is a heightened tissue inflammatory response. The strongest genetic association is with HLA B51. There are immunological aberrations but not prominent enough to call it an autoimmune disease. Similarly, Behçet’s syndrome does not fit easily into the broad concept of autoinflammatory diseases. The histopathology is also non-specific and the diagnosis is mainly clinical. Differentiation from Crohn’s disease is very difficult. In more than one-half of the patients the disease burns out in time, thus only symptomatic therapy is indicated in some patients. However, eye involvement, pulmonary vascular disease, thrombophilic complications, CNS involvement, and gastrointestinal disease need prompt recognition and treatment. Brief courses of glucocorticosteroids along with immunosuppressives including the newer biologicals, interferon, and colchicine are commonly used. However, controlled clinical trials are not available for some of these medications especially when thrombophilia, CNS, and gastrointestinal disease are present.
Macrophage activation syndrome
Authors: Grom Alexei A. , Ramanan Athimalaipet V.
Published: February 2018

Macrophage activation syndrome (MAS) is a life-threatening condition caused by excessive activation and proliferation of T lymphocytes and haemophagocytic macrophages. Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic juvenile idiopathic arthritis. Flares of the underlying disease or infection are most common triggers of MAS. The pathognomonic feature of MAS is typically found in bone marrow: numerous, well-differentiated macrophagic histiocytes phagocytosing normal haematopoietic elements. The expansion of these histiocytes leads to a massive systemic inflammatory reaction associated with three cardinal clinical features: severe cytopenias, liver dysfunction, and coagulopathy consistent with disseminated intravascular coagulation.
Clinically, MAS is strikingly similar to the autosomal recessive disorders collectively known as familial haemophagocytic lymphohistiocytosis (FHLH). FHLH has been associated with various genetic defects affecting the cytolytic pathway. Cytolytic function is profoundly depressed in MAS patients as well, and this abnormality is caused by both genetic and acquired factors.
Studies in animals suggest that uncontrolled expansion of activated CD8+ T lymphocytes secreting cytokines that activate macrophages is central to the pathophysiology of haemophagocytic syndromes. Consistent with this view, the combination of steroids and ciclosporin, an immunosuppressant that preferentially inhibits T lymphocytes, is an effective treatment for the majority of MAS patients. Patients in whom MAS remains active despite this treatment present a serious challenge and require more aggressive immunosuppression. However, in MAS triggered by infection, the optimal level of immunosuppression is difficult to determine. As a result, reported mortality rates reach 20%.
ST-segment elevation MI
Authors: Cheong Adrian P. , Steg Gabriel , James Stefan K.
Published: February 2018

Acute myocardial infarction with ST-segment elevation is a common and dramatic manifestation of coronary artery disease. It is caused by the rupture of an atherosclerotic plaque in a coronary artery, leading to its total thrombotic occlusion and resultant ischaemia and necrosis of downstream myocardium. The diagnosis of ST-segment elevation myocardial infarction is based on a syndrome of ischaemic chest pain symptoms, associated with typical ST-segment elevation on the electrocardiogram and an eventual rise in biomarkers of myocardial necrosis. The treatment of ST-segment elevation myocardial infarction is focused on re-establishing blood flow in the coronary artery involved, preferably by percutaneous coronary intervention, or by pharmacological thrombolysis in the case of expected lengthy time delays or lack of availability of facilities. Early mortality from ST-segment elevation myocardial infarction can be attributed to the sequelae or complications of myocardial ischaemia, or complications related to therapy. The former include arrhythmias (such as ventricular tachycardia or fibrillation), mechanical complications (such as ventricular free wall, septal, and mitral chordal rupture), and pump failure leading to cardiogenic shock. The latter includes haemorrhagic complications and coronary stent thrombosis. Given that myocardial necrosis is a critically time-dependent process, the organization of an ST-segment elevation myocardial infarction care system and adherence to the latest clinical trial evidence and guidelines are crucial to ensure that patients are treated in an optimal manner.
Acute respiratory failure and acute respiratory distress syndrome
Authors: Gattinon Luciano , Carlesso Eleonora
Published: February 2018

Respiratory failure (RF) is defined as the acute or chronic impairment of respiratory system function to maintain normal oxygen and CO2 values when breathing room air. ‘Oxygenation failure’ occurs when O2 partial pressure (PaO2) value is lower than the normal predicted values for age and altitude and may be due to ventilation/perfusion mismatch or low oxygen concentration in the inspired air. In contrast, ‘ventilatory failure’ primarily involves CO2 elimination, with arterial CO2 partial pressure (PaCO2) higher than 45 mmHg. The most common causes are exacerbation of chronic obstructive pulmonary disease (COPD), asthma, and neuromuscular fatigue, leading to dyspnoea, tachypnoea, tachycardia, use of accessory muscles of respiration, and altered consciousness. History and arterial blood gas analysis is the easiest way to assess the nature of acute RF and treatment should solve the baseline pathology. In severe cases mechanical ventilation is necessary as a ‘buying time’ therapy. The acute hypoxemic RF arising from widespread diffuse injury to the alveolar-capillary membrane is termed Acute Respiratory Distress Syndrome (ARDS), which is the clinical and radiographic manifestation of acute pulmonary inflammatory states.
Supraorbital vs Endo-Orbital Routes to the Lateral Skull Base: A Quantitative and Qualitative Anatomic Study
Authors: Di Somma Alberto , Andaluz Norberto , Cavallo Luigi Maria , Keller Jeffrey T , Solari Domenico , Zimmer Lee A , de Notaris Matteo , Zuccarello Mario , Cappabianca Paolo
Published: February 2018

BACKGROUND

Various extensions of the supraorbital approach reach the lateral and parasellar middle cranial fossa regions by removing the orbital rim and greater/lesser sphenoid wings. Recent proposals of a purely endoscopic ventral transorbital pathway to these regions heighten the need to compare these surgical windows.

OBJECTIVE

To detail the lateral and parasellar middle cranial fossa regions and quantify exposures by 2 surgical windows (transcranial and transorbital) through anatomic study.

METHODS

In 5 cadaveric specimens (10 sides), dissections consisted of 3 stages: stage 1 began with the supraorbital approach via the eyebrow; stage 2, endo-orbital approach via the superior eyelid, continued with removal of lesser and greater sphenoid wings; and stage 3, extended supraorbital, re-evaluated the gains of stage 2 from the perspective of stage 1. Operative working areas were quantified in Sylvian, anterolateral temporal, and parasellar regions; bone removal volumes were measured at each stage (nonpaired Student t-test).

RESULTS

Visualization into the anterolateral temporal and Sylvian areas, though varied in perspective, were comparable with either eyelid or transcranial routes. Compared with transcranial views through a supraorbital window, the eyelid approach significantly increased exposure in the parasellar region with wider angle of attack (P < .01) and achieved comparable bone removal volumes.

CONCLUSION

Stage 2’s unique anatomic view of the lateral and parasellar middle cranial fossa regions paves the way for possible surgical application to select pathologies typically treated via transcranial approaches. Disadvantages may be the surgeon's unfamiliarity with the anatomy of this purely endoscopic, ventral route and difficulties of dural and orbital repair.
Evaluation of alternative fabrication specifications to increase gross value of pork carcasses
Authors: Bryan Erin E , Overholt Martin F , Kim Gap Don , Dilger Anna C , Boler Dustin D
Published: February 2018

Modifying fabrication specifications of domestic pork carcasses to reflect product specifications in key export markets may increase gross value for U.S. pork. Changes in specifications may also yield value-added cuts that increase demand for U.S. pork in both export and domestic markets. The objective was to evaluate differences in value of carcasses fabricated using either typical U.S. cutting specifications, or alternative specifications. Paired left and right sides (30 sides total; n = 15) were weighed and cut into primal and subprimal pieces according North American Meat Institute (NAMP, DOM) or alternative-style specifications (ALT). Alternative-style carcasses were separated into shoulder (4th/5th rib separation), loin, belly, and ham (sirloin-on) primals. Alternative-style shoulders were fabricated into a cellar-trimmed (CT) butt, triceps brachii (cushion), boneless picnic, and a brisket. Carcass values for all three pricing scenarios were calculated using the USDA Agriculture Marketing Service Carlot Report values from the weeks of April 5, 2013, to April 7, 2017. Value for the pork brisket was estimated based on relative value of the beef brisket compared to the beef shoulder clod (NAMP #114) resulting in a value of $2.485/kg for the pork brisket. Comparisons between fabrication styles and value of each side were made using a paired T-test. Whole bone-in loin yields of ALT carcasses were 6.23 units less (P < 0.0001) than DOM carcasses. Similarly, yields from trimmed and squared bellies of ALT carcasses were 0.83 units less than (P ≤ 0.01) DOM carcasses. In contrast, trimmed shoulders of ALT carcasses were 3.81 units greater (P < 0.0001) and hams were 3.39 units greater (P < 0.0001) than DOM carcasses. Despite reductions in yield of loins and bellies, ALT carcasses were numerically $1.29 (P = 0.17) and $0.66 (P = 0.56) more valuable than DOM carcasses in the 4 yr average and best pricing scenarios, respectively. Alternative-style carcasses were $1.99 (P = 0.03) more valuable than DOM carcass when using the most depressed pricing scenario. Fabricating pork carcasses using alternative-style specifications reduced the yield, and therefore the value, of the loin and belly compared with DOM carcasses. However, added value from the pork brisket and CT butt recuperated this value. Therefore, alternative-style fabrication methods may increase gross carcass value in some pricing scenarios.
PA program characteristics and diversity in the profession
Authors: Coplan Bettie , Bautista Tara G. , Dehn Richard W.
Published: February 2018

Objectives:

The primary objective of this study was to identify PA program characteristics that may be associated with higher or lower percentages of underrepresented minority students in PA programs.

Methods:

Data from the Physician Assistant Education Association (PAEA) 2002-2003 and 2012-2013 annual surveys were analyzed. Bivariate correlation coefficients and multiple regression modeling were used to identify relationships between program characteristics and percentages of black and Hispanic students.

Results:

The percentage of white matriculants in PA programs increased from 76.5% in 2002-2003 to 81.8% in 2012-2013; the percentage of black students decreased from 6.2% to 4.4%. Multiple linear regression revealed a modest negative relationship between master's degree and percentage of underrepresented minority students and a modest positive relationship between percentages of underrepresented minority employees and underrepresented minority students.

Conclusions:

Further research is needed to identify strategies to increase underrepresented minority participation in healthcare professions programs.
Addressing HIV Stigma in Health Care
Authors: Davtyan Mariam , Olshansky Ellen F. , Lakon Cynthia
Published: February 2018

Strategies to address this potent barrier to treatment and prevention.
The Usability and Acceptability of a Patient-Centered Mobile Health Tracking App Among a Sample of Adult Radiation Oncology Patients
Authors: Birkhoff Susan D. , Cantrell Mary Ann , Moriarty Helene , Lustig Robert
Published: February 2018

The usability and acceptability of patient-centered mobile health tracking apps among most clinical populations are unknown. This mixed-methods feasibility study evaluated the usability and acceptability of the Health Storylines app among 32 adult radiation oncology patients in a 2-week trial. Data were collected via pre– and post–app use surveys and digital analytics. Participants accessed the app platform a total of 711 times. The overall usability of the Heath Storylines app was rated favorably, and 81% of participants reported the app easy to use. This study provides beginning evidence of the usability and acceptability of this type of mobile health tracking app in adult oncology patients.
The Nursing Knowledge Pyramid
Authors: Decker Veronica B. , Hamilton Roger M.
Published: February 2018

A theory of the structure of nursing knowledge is proposed. Using retroductive reasoning to build upon an existing theory, the goal of the Nursing Knowledge Pyramid is to integrate disparate forms of nursing knowledge into a comprehensive, coherent, and useful structure to enhance the learning, development, automation, and accessibility of nursing knowledge. Education uses are discussed.
National Partnership for Maternal Safety
Authors: Lagrew David C. , Low Lisa Kane , Brennan Rita , Corry Maureen P. , Edmonds Joyce K. , Gilpin Brian G. , Frost Jennifer , Pinger Whitney , Reisner Dale P. , Jaffer Sara
Published: February 2018

Cesarean births and associated morbidity and mortality have reached near epidemic proportions. The National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care responded by developing a patient safety bundle to reduce the number of primary cesarean births. Safety bundles outline critical practices to implement in every maternity unit. This National Partnership for Maternity Safety bundle, as with other bundles, is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Bundle components may be adapted to individual facilities, but standardization within an institution is advised. Evidence-based resources and recommendations are provided to assist implementation.
IDENTIFICATION OF POSTERIOR SEGMENT PATHOLOGY WITH EN FACE RETINAL IMAGING USING MULTICOLOR CONFOCAL SCANNING LASER OPHTHALMOSCOPY
Authors: Feng Henry L. , Sharma Sumit , Stinnett Sandra , Asrani Sanjay , Mruthyunjaya Prithvi
Published: February 2018

Purpose:

To assess posterior segment findings on multicolor confocal scanning laser ophthalmoscopy by correlation with spectral domain optical coherence tomography (SD-OCT) and to quantify agreement between these imaging modalities.

Methods:

Retrospective review of 159 eyes of 96 consecutive patients who underwent concurrent imaging with multicolor confocal scanning laser ophthalmoscopy and SD-OCT. Positive percent agreement and negative percent agreement were calculated for each finding identified on infrared, green, blue, and multicolor reflectance images using SD-OCT as a comparator.

Results:

Infrared reflectance best detected outer retinal and choroidal findings such as choroidal lesions, retinal pigment epithelium atrophy, peripapillary atrophy, and drusen (positive percent agreement 100, 92, 92, and 67%, respectively). Inner retinal changes including epiretinal membrane, lamellar macular hole, and inner retinal alterations were best detected on blue reflectance (positive percent agreement 94, 50, and 100%, respectively). Composite multicolor reflectance most effectively detected conditions with retinal elevation, including pigment epithelial detachment, intraretinal fluid, and subretinal fluid (positive percent agreement 65, 49, and 54%, respectively). Multicolor confocal scanning laser ophthalmoscopy detected intraretinal and subretinal hemorrhages, which were not detected on SD-OCT (negative percent agreement 87 and 97%, respectively).

Conclusion:

Multicolor confocal scanning laser ophthalmoscopy is capable of identifying posterior segment pathology at various anatomical depths and may be a useful adjunct to SD-OCT for detecting or monitoring certain retinal conditions.
Recognition of Fungal Keratitis in Boston Type I Keratoprosthesis: Importance of Awareness and Novel Identification of Exophiala phaeomuriformis
Authors: Machen Lindsay , Chau Felix Y. , de la Cruz Jose , Sugar Joel , Cortina Maria Soledad
Published: February 2018

Purpose:

To present a case of Exophiala phaeomuriformis fungal keratitis to demonstrate the heightened concern for fungal infection in patients with a keratoprosthesis and to highlight the rare involvement of Exophiala phaeomuriformis.

Methods:

Case report.

Results:

Exophiala phaeomuriformis was identified in a susceptible patient 7 years after Boston type I keratoprosthesis (KPro) implantation.

Conclusions:

Although fungal infiltration after KPro placement does not represent a novel clinical infection, identification of the rare Exophiala species in a patient with a KPro has not been reported and provides an opportunity for reflection on fungal identification, prophylaxis, and prevention in this vulnerable patient population.
Switching Between Antibiotics Among Danish Children 0–4 Years of Age
Authors: Reilev Mette , Thomsen Reimar W. , Aabenhus Rune , Sydenham Rikke V. , Hansen Jens Georg , Pottegård Anton
Published: February 2018

Background:

In Denmark, the use of amoxicillin is widespread among children, despite phenoxymethylpenicillin being recommended as first-line therapy. The reason for this apparent discrepancy is not fully understood. We aimed at evaluating prescribing patterns of antibiotics among Danish children 0–4 years of age, with emphasis on incidence of treatment episodes, choice of initial antibiotic treatment and switching patterns between different types of antibiotics.

Methods:

We identified all children ≤4 years of age who filled a prescription of antibiotics from 2000 to 2015 according to the nationwide Danish National Prescription Registry. We estimated the incidence rate of episodes treated with antibiotics and the choice of initial antibiotic treatment over time. Further, we assessed the cumulative risk of switching within 0–3 days after initiating therapy.

Results:

We identified 3,481,684 antibiotic treatment episodes issued to 0- to 4-year-olds from 2000 to 2015. The incidence rate was stable until 2011 both among children 0–1 years of age (approximately 880/1000) and among children 2–4 years of age (approximately 610/1000), after which it dropped. Phenoxymethylpenicillin and, increasingly, amoxicillin were most frequently used as initial treatments (39% vs. 44%). Few switched from amoxicillin (1%) or phenoxymethylpenicillin (4.7%) within the first 3 days. Of those who switched from phenoxymethylpenicillin, 64% received amoxicillin as second-line treatment.

Conclusions:

The incidence of episodes treated with antibiotics among Danish children 0–4 years of age has decreased considerably since 2011. In contrast to guideline recommendations, amoxicillin is the most frequently used initial treatment. Early switching between antibiotics is uncommon. Initiatives should address the extensive use of amoxicillin.
Longitudinal Changes in Body Composition by Dual-energy Radiograph Absorptiometry Among Perinatally HIV-infected and HIV-uninfected Youth
Authors: Sharma Tanvi S. , Somarriba Gabriel , Arheart Kristopher L. , Neri Daniela , Mathew M. Sunil , Graham Patricia L. , Scott Gwendolyn B. , Miller Tracie L.
Published: February 2018

Background:

Combination antiretroviral therapy has allowed youth with perinatal HIV infection (PHIV+) to live into adulthood, but many youth may experience metabolic and body composition changes that predispose to greater cardiovascular disease (CVD) risk. This longitudinal study evaluated changes in body composition measured by dual-energy radiograph absorptiometry (DXA) in a cohort of PHIV+ youth compared with HIV− controls over a 7-year period.

Methods:

PHIV+ youth and HIV− controls were prospectively enrolled in a single-site study to assess nutrition and CVD risk. Anthropometrics and DXA scans were longitudinally obtained to assess percent body fat and regional fat distribution. Using general linear models, we analyzed differences in body composition and anthropometric measures by sex between PHIV+ youth and controls over time.

Results:

Two hundred thirty-five participants (156 PHIV+ and 79 HIV− controls) with at least 1 DXA performed since study enrollment were included for analysis. During the study period, 471 DXAs were obtained in the PHIV+ group and 95 in HIV− controls. PHIV+ females demonstrated greater increase in weight and body mass index over time compared with HIV− females, and significant increases in total percent body fat [estimate = 1.212 (95% confidence interval: 0.837–1.587) percent per year; P < 0.001) and percent trunk fat [1.3818 (95% confidence interval: 0.922–1.84); P < 0.001] compared with HIV− females and PHIV+ males.

Conclusions:

PHIV+ females demonstrate an unfavorable change in fat redistribution and percent body fat over time that exceeds the pattern seen in PHIV+ males or HIV− females. Providers should have heightened awareness of body composition changes of PHIV+ females that may eventually lead to increased CVD risk.
Pharmacokinetics, Short-term Safety and Efficacy of the Approved Once-daily Darunavir/Ritonavir Dosing Regimen in HIV-infected Children
Authors: Bastiaans Diane E. T. , Geelen Sibyl P. M. , Visser Eline G. , van der Flier Michiel , Vermont Clementien L. , Colbers Angela P. H. , Roukens Monique , Burger David M. , van Rossum Annemarie M. C.
Published: February 2018

In this multicenter pharmacokinetic study in HIV-infected children (6–12 years of age), we validated the approved once-daily darunavir/ritonavir dosing recommendations. The geometric mean darunavir area under the plasma concentration-time curve was 63.1 h·mg/L, substantially lower than the mean value observed in adults. However, all trough levels were adequate, and short-term virologic outcome was good. These data support the use of the darunavir/ritonavir once-daily dosing recommendations.
Moving Toward Paying for Outcomes in Medicaid
Authors: Millwee Billy , Quinn Kevin , Goldfield Norbert
Published: February 2018

Medicaid can improve beneficiary health and help sustain its own future by embracing payment for outcomes. Good precedents exist from states such as Florida, Maryland, Minnesota, New York, Ohio, Pennsylvania, and Texas. Medicaid outcome measures include preventable admissions, readmissions, emergency department visits, and inpatient complications; early elective deliveries; infant and child mortality; patient-reported outcomes, satisfaction, and confidence; and reduction in low-value care. Criteria to prioritize initiatives include potential savings, availability of established models, impact on health status, and Medicaid's ability to effect change. We offer 5 principles for success, emphasizing clinically credible initiatives that generate actionable information for clinicians.
Severity of Illness Measures for Pediatric Inpatients
Authors: Hessels Amanda J. , Liu Jianfang , Cohen Bevin , Shang Jingjing , Larson Elaine L.
Published: February 2018

Introduction:

Severity of illness (SOI) measures are commonly used in adults for comparison of treatment and outcomes in similar populations. Less is known about the psychometric properties of measures available to providers and healthcare systems caring for pediatric patients. The purpose of this study was to (1) identify SOI measures used for pediatric patients admitted to acute care hospitals and (2) compare the ability of two SOI measures to predict mortality and length of stay (LOS).

Methods:

Twelve instruments were identified through literature search and one, the pediatric chronic complex condition (CCC), was retained. The CCC and the Charlson/Deyo comorbidity score were applied to an 8-year retrospective, multi-institutional data set using logistic and zero-truncated negative binomial regression models.

Results:

Records from 199,001 children were examined. The CCC performed better for predicting mortality (odds ratio = 3.36; 95% confidence interval [CI]: 3.20–3.53) and LOS (incidence rate ratio = 2.24; 95% CI: 2.22–2.26).

Conclusions:

The CCC may be preferable for predicting outcomes among pediatric inpatients. Pediatric SOI measures are not extensively developed and tested nor widely and freely available. The use of the CCC can predict mortality and LOS to guide care, resource allocation, and research for the pediatric population.
Management of Early Cervical Stromal Invasion FIGO Stage 1A1 When Margins Are Involved With Cervical Intraepithelial Neoplasia
Authors: Nicholson Rachel C. , Twigg Jeremy , Roberts Alison , Angelopoulos Georgios , Cruickshank Derek
Published: February 2018

Objective

Women with International Federation of Gynecology and Obstetrics stage 1A1 cervical carcinoma were evaluated to determine whether repeat excision for large loop excision transformation zone margins positive with cervical intraepithelial neoplasia (CIN) had been undertaken according to the National Health Service Cervical Screening Programme guidelines and if deviations from guidelines adversely affected patient outcome.

Materials and Methods

We retrospectively studied patients with 1A1 cervical carcinoma treated in our service between May 2010 and July 2015 to determine whether NHSCSP guidelines (May 2010) were followed. This states that if the invasive disease is excised but CIN extends to the excision margin, then a repeat large loop excision transformation zone should be undertaken to exclude further invasive disease and to confirm excision of CIN.

Results

Seventeen patients were identified. In one, neither the invasive lesion nor CIN was fully excised. In 5, the lesion and CIN were fully excised. In eleven, the invasive lesion was excised, but CIN was present at a margin. Of these 11 patients, none opted for a repeat excision. All 11 patients had negative cytology at first follow-up (negative up to 4 years [median = 2 years]).

Conclusions

Our outcomes suggest that it may not be necessary to perform a repeat excision for CIN present at the excision margin in women with 1A1 cervical carcinoma when CIN is present either at the endocervical, deep stromal, or ectocervical margin, as long as the invasive focus is fully excised, and patients have been fully counseled and have regular cytology follow-up. This may be an alternative for patients wanting to minimize the risks to fertility posed by repeat excision.
Twenty-Five Years of Lamivudine: Current and Future Use for the Treatment of HIV-1 Infection
Authors: Quercia Romina , Perno Carlo-Federico , Koteff Justin , Moore Katy , McCoig Cynthia , St. Clair Marty , Kuritzkes Daniel
Published: February 2018

Innovation in medicine is a dynamic, complex, and continuous process that cannot be isolated to a single moment in time. Anniversaries offer opportunities to commemorate crucial discoveries of modern medicine, such as penicillin (1928), polio vaccination (inactivated, 1955; oral, 1961), the surface antigen of the hepatitis B virus (1967), monoclonal antibodies (1975), and the first HIV antiretroviral drugs (zidovudine, 1987). The advent of antiretroviral drugs has had a profound effect on the progress of the epidemiology of HIV infection, transforming a terminal, irreversible disease that caused a global health crisis into a treatable but chronic disease. This result has been driven by the success of antiretroviral drug combinations that include nucleoside reverse transcriptase inhibitors such as lamivudine. Lamivudine, an L-enantiomeric analog of cytosine, potently affects HIV replication by inhibiting viral reverse transcriptase enzymes at concentrations without toxicity against human polymerases. Although lamivudine was approved more than 2 decades ago, it remains a key component of first-line therapy for HIV because of its virological efficacy and ability to be partnered with other antiretroviral agents in traditional and novel combination therapies. The prominence of lamivudine in HIV therapy is highlighted by its incorporation in recent innovative treatment strategies, such as single-tablet regimens that address challenges associated with regimen complexity and treatment adherence and 2-drug regimens being developed to mitigate cumulative drug exposure and toxicities. This review summarizes how the pharmacologic and virologic properties of lamivudine have solidified its role in contemporary HIV therapy and continue to support its use in emerging therapies.
High Prevalence of Antithyroid Antibodies in a New Zealand Cohort of Patients With Systemic Sclerosis
Authors: Solanki Kamal K. , Al-Majmuei Mahmood , White Douglas H. N.
Published: February 2018

Background

Autoimmune thyroid disease affects 1% of the general population, and autoimmune thyroid antibodies are noted in up to 15%.

Objective

We hypothesized systemic sclerosis (SSc) is associated with higher prevalence of antithyroglobulin (anti-Tg) and anti–thyroid peroxidase (anti-TPO) antibodies) to justify monitoring of thyroid function for earlier detection and treatment.

Methods

Waikato Hospital SSc clinic patients were prospectively tested for thyroid function tests and antithyroid antibodies (ATAs).

Results

Of the 75 patients with SSc and 10 patients with SSc overlap syndrome (SOS) followed up in the SSc clinic, anti-Tg and anti-TPO were prospectively tested in 61 (70.6%) of the 85 patients. The cohort comprised 38 patients with limited cutaneous SSc (lcSSc), 15 with diffuse cutaneous SSc, and 8 with SOS.

Anti-Tg and anti-TPO antibodies were found in 34.2% in lcSSc patients and 33.3% in diffuse cutaneous SSc patients, whereas in SOS they were found in 25% (Tg) and in 12.5% (TPO) of patients.

At baseline, 10 patients (11.7%) had thyroid dysfunction: 8 (9.4%) with subclinical hypothyroidism and 1 each (1.2%) with subclinical hyperthyroidism and with clinical hyperthyroidism.

After 18 months, 1 woman with lcSSc, positive for both ATAs, developed clinical hypothyroidism.

Conclusions

There is a higher prevalence of ATAs in SSc and SOS compared with the general population. Screening these patients for ATAs is a reasonable measure.
Online Physician Reviews in Female Pelvic Medicine and Reconstructive Surgery: What Do Patients Really Want?
Authors: Asanad Kian , Parameshwar Pooja S. , Houman Justin , Spiegel Brennan M. , Daskivich Timothy J. , Anger Jennifer T.
Published: February 2018

Objectives

This study aimed to qualitatively analyze online reviews of Female Pelvic Medicine and Reconstructive Surgery (FPMRS) specialists to better understand patients' experiences and improve patient satisfaction.

Methods

Fifty urologists and urogynecologists were randomly sampled from the Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction membership website. We evaluated patient ratings and reviews of physicians from 4 websites: Yelp, Healthgrades, Vitals, and UCompareHealthCare. Qualitative data analysis was performed using grounded theory methodology, as described by Charmaz (Constructing Grounded Theory, 2014).

Results

Across the four websites, the mean number of stars per physician ranged from 3.6 to 4.1 and the mean number of reviews per physician ranged from 1.3 to 7.6. Qualitative analysis revealed several preliminary themes: patient–physician experience, medical and surgical treatment, office staff, and analysis of worth. Physicians who developed strong connections with patients through empathetic communication were likely to receive a positive review, regardless of wait times. Bedside manner was found to be multidimensional and included physician competence and understanding patients' concerns. Failure to meet several expectations led to dissatisfaction of care and negative patient reviews.

Conclusions

Patients' perspectives of quality of care in FPMRS are weighted heavily toward establishing personal connections with physicians. Accurate diagnosis and effective management of urological conditions, especially after negative experiences with previous providers, were associated with satisfaction of care. It seems that the concept of good bedside manner is multifactorial and requires the provider to demonstrate not one but several different sets of communication skills.
The effect of mutational robustness on the evolvability of multicellular organisms
Authors: Jiang Pengyao , Kreitman Martin , Reinitz John
Published: February 2018

Canalization involves mutational robustness, the lack of phenotypic change as a result of genetic mutations. Given the large divergence in phenotype across species, understanding the relationship between high robustness and evolvability has been of interest to both theorists and experimentalists. Although canalization was originally proposed in the context of multicellular organisms, the effect of multicellularity on evolvability has not been considered by theoreticians. We address this issue using a Boolean population model with explicit representation of an environment in which multicellular individuals with explicit genotype and phenotype evolve. Robustness is described by a single real number between zero and one. We find that high robustness is favored in constant environments, and lower robustness is favored after environmental change. Multicellularity severely constrains robustness: peak evolvability occurs at an absolute level of robustness of about 0.99 compared with values of about 0.5 in a classical neutral network model. Multicellularity results in a sharp peak of evolvability in which the maximum is set by the fact that the fixation of adaptive mutations becomes more improbable as robustness decreases. When robustness is put under genetic control, robustness levels leading to maximum evolvability are selected for, but maximal relative fitness appears to require recombination.
Partial-Width Injuries of the Rat Rotator Cuff Heal with Fibrosis
Authors: Lemmon Elisabeth A. , Locke Ryan C. , Szostek Adrianna K. , Killian Megan L.
Published: February 2018

Purpose

The purpose of this study was to identify the healing outcomes following a partial-width, full-thickness injury to the rotator cuff tendon-bone attachment and establish if the adult attachment can regenerate the morphology of the healthy attachment.

Hypothesis

We hypothesized that a partial-width injury to the attachment would heal via fibrosis and bone remodeling, resulting in increased cellularity and extracellular matrix deposition, reduced bone volume, osteoclast presence and decreased collagen organization compared to shams.

Materials and Methods

A biopsy punch was used to create a partial-width injury at the center one-third of the rat infraspinatus attachment, and the contralateral limb underwent a sham operation. Rats were sacrificed at 3- and 8-weeks after injury for analyses. Analyses performed at each time-point included cellularity (Hematoxylin & Eosin), ECM deposition (Masson’s Trichrome), bone volume (micro-computed tomography; microCT), osteoclast activity (Tartrate Resistant Acid Phosphatase; TRAP), and collagen fibril organization (Picrosirius Red). Injured and sham shoulders were compared at both 3- and 8-weeks using paired, two-way ANOVAs with repeated measures and Sidak’s correction for multiple comparisons.

Results

Cellularity and ECM deposition increased at both 3- and 8-weeks compared to sham contralateral attachments. Bone volume decreased and osteoclast presence increased at both 3- and 8-weeks compared to sham contralateral limbs. Collagen fibril organization was reduced at 3-weeks after injury compared to 3-week sham attachments.

Conclusions

These findings suggest that a partial-width injury to the rotator cuff attachment does not fully regenerate the native structure of the healthy attachment. The injury model healed via scar-like fibrosis and did not propagate into a full-width tear after 8-weeks of healing.