bluuebunny/crossref_metadata_2025 huggingface dataset:
ReadXplorer 2—detailed read mapping analysis and visualization from one single source
Authors: Hilker Rolf , Stadermann Kai Bernd , Schwengers Oliver , Anisiforov Evgeny , Jaenicke Sebastian , Weisshaar Bernd , Zimmermann Tobias , Goesmann Alexander
Published: August 2016

Motivation: The vast amount of already available and currently generated read mapping data requires comprehensive visualization, and should benefit from bioinformatics tools offering a wide spectrum of analysis functionality from just one source. Appropriate handling of multiple mapped reads during mapping analyses remains an issue that demands improvement.

Results: The capabilities of the read mapping analysis and visualization tool ReadXplorer were vastly enhanced. Here, we present an even finer granulated read mapping classification, improving the level of detail for analyses and visualizations. The spectrum of automatic analysis functions has been broadened to include genome rearrangement detection as well as correlation analysis between two mapping data sets. Existing functions were refined and enhanced, namely the computation of differentially expressed genes, the read count and normalization analysis and the transcription start site detection. Additionally, ReadXplorer 2 features a highly improved support for large eukaryotic data sets and a command line version, enabling its integration into workflows. Finally, the new version is now able to display any kind of tabular results from other bioinformatics tools.

Availability and Implementation:  http://www.readxplorer.org

Contact:  readxplorer@computational.bio.uni-giessen.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Currents of Neo-Liberalism: British Political Ideologies and the New Right, c.1955–1979
Authors: Jackson Ben
Published: August 2016

This article investigates the emergence of neo-liberalism in Britain and its intellectual relationship with each of the three main British political ideologies. The article distinguishes between different currents of neo-liberalism that have been absorbed into British political thought, and shows that this process to some extent pre-dated the electoral success of Thatcherism in the 1980s. The article further suggests that labelling recent British political discourse as unvarnished ‘neo-liberalism’, while at times analytically useful, simplifies a more complicated picture, in which distinctively neo-liberal ideas have been blended in different ways into the ideologies of British Liberalism, Conservatism and even Labour socialism. The article therefore turns the spotlight on a more obscure aspect of the making of British neo-liberalism by exploring how politicians and intellectuals of varying partisan stripes generated policy discourses that presented neo-liberal ideas as an authentic expression of their own ideological traditions. Perhaps the most surprising finding of this article, then, is that neo-liberalism, although frequently characterised as rigid and dogmatic, has in fact proved itself to be a flexible and adaptable body of ideas, capable of colonising territory right across the political spectrum.
A mixed methods study of clinical information availability in obstetric triage and prenatal offices
Authors: Meyerhoefer Chad D , Sherer Susan A , Deily Mary E , Chou Shin-Yi , Peng Lizhong , Hu Tianyan , Nihen Marion , Sheinberg Michael , Levick Donald
Published: August 2016

Objective: To determine the effect of availability of clinical information from an integrated electronic health record system on pregnancy outcomes at the point of care.

Materials and methods: We used provider interviews and surveys to evaluate the availability of pregnancy-related clinical information in ambulatory practices and the hospital, and applied multiple regression to determine whether greater clinical information availability is associated with improvements in pregnancy outcomes and changes in care processes. Our regression models are risk adjusted and include physician fixed effects to control for unobservable characteristics of physicians that are constant across patients and time.

Results: Making nonstress test results, blood pressure data, antenatal problem lists, and tubal sterilization requests from office records available to hospital-based providers is significantly associated with reductions in the likelihood of obstetric trauma and other adverse pregnancy outcomes. Better access to prenatal records also increases the probability of labor induction and decreases the probability of Cesarean section (C-section). Availability of lab test results and new diagnoses generated in the hospital at ambulatory offices is associated with fewer preterm births and low-birth-weight babies.

Discussion and conclusions: Increased availability of specific clinical information enables providers to deliver better care and improve outcomes, but some types of clinical data are more important than others. More available information does not always result from automated integration of electronic records, but rather from the availability of the source records. Providers depend upon information that they trust to be reliable, complete, consistent, and easily retrievable, even if this requires multiple interfaces.
A clinical care pathway to improve the acute care of patients with glioma
Authors: Riblet Natalie B.V. , Schlosser Evelyn M. , Snide Jennifer A. , Ronan Lara , Thorley Katherine , Davis Melissa , Hong Jennifer , Mason Linda P. , Cooney Tobi J. , Jalowiec Lanelle , Kennedy Nancy L. , Richie Sabrina , Nalepinski David , Fadul Camilo E.
Published: August 2016

Background

Patients with glioma are at increased risk for tumor-related and treatment-related complications. Few guidelines exist to manage complications through supportive care. Our prior work suggests that a clinical care pathway can improve the care of patients with glioma.

Methods

We designed a quality improvement (QI) project to address the acute care needs of patients with gliomas. We formed a multidisciplinary team and selected 20 best-practice measures from the literature. Using a plan-do-study-act framework, we brainstormed and implemented various improvement strategies starting in October 2013. Statistical process control charts were used to assess progress.

Results

Retrospective data were available for 12 best practice measures. The baseline population consisted of 98 patients with glioma. Record review suggested wide variation in performance, with compliance ranging from 30% to 100%. The team hypothesized that lack of process standardization may contribute to less-than-ideal performance. After implementing improvement strategies, we reviewed the records of 63 consecutive patients with glioma. The proportion of patients meeting criteria for 12 practice measures modestly improved (65% pre-QI; 76% post-QI, P > .1). Unexpectedly, a higher proportion of patients were readmitted within 30 days of hospital discharge (pre-QI: 10%; post-QI: 17%, P > .1). Barriers to pathway development included difficulties with transforming manual measures into electronic data sets.

Conclusions

Creating evidence-based clinical care pathways for addressing the acute care needs of patients with glioma is feasible and important. There are many challenges, however, to developing sustainable systems for measuring and reporting performance outcomes overtime.
Aurora candidates from the chronicle of Qíng dynasty in several degrees of relevance
Authors: Kawamura Akito D. , Hayakawa Hisashi , Tamazawa Harufumi , Miyahara Hiroko , Isobe Hiroaki
Published: August 2016

We present the result of a survey of sunspots and auroras in Qíngshǐgǎo (清史稿), a draft chronicle of Qíng dynasty, for the period of 1559–1912 CE. This is a sequel to a series of works surveying historical sunspot and aurora records, and providing online data to the scientific community regarding the attained results. In total of this Qíngshǐgǎo survey, we found 111 records of night-sky luminous events with such keywords as vapor (氣, qì), cloud (雲, yún), and light (光, guāng), which may indicate auroras as well as some other phenomena. Similarly, a keyword survey for sunspots was conducted, but no sunspot record was found. In comparison with the aurora records in the western world, we found that 14 of the 111 records have a corresponding record of simultaneous observation in the western world, and hence are very likely to be aurora. In order to investigate the likeliness of the remainder of the record being aurora, we calculated the lunar age and the phase of a solar cycle for each record. After these calculations, a notable fraction of these records clustered near the full moon were to be found statistically doubtful in considerations with atmospheric optics; meanwhile, a few records of observations near the new moon could be more likely interpreted as being auroras, including three records during the Maunder minimum.
A Meta-Analysis of the Worldwide Prevalence of Pica during Pregnancy and the Postpartum Period
Authors: Fawcett E.J. , Fawcett J.M. , Mazmanian D.
Published: August 2016

(Int J Gynaecol Obstet. 2016;133(3):277–283)

Pica, the purposeful consumption of nonfood or non-nutritive substances, is commonly reported in women during the period surrounding childbirth. However, the Diagnostic and Statistical Manual of Mental Disorders-5 does not provide a prevalence estimate for pica, and current prevalence estimates during pregnancy range from 0.007% in Denmark to 92.5% in Nigeria. In this meta-analysis, authors estimated the prevalence of pica in pregnant and postpartum populations and characterized potential contributing factors/moderators.
Prophylactic Intravenous Ephedrine to Minimize Fetal Bradycardia After Combined Spinal-epidural Labour Analgesia: A Randomized Controlled Study
Authors: Gambling D.R. , Bender M. , Faron S. , Glaser D. , Farrell T.R.
Published: August 2016

(Can J Anaesth. 2015;62(11):1201–1208)

The combined spinal-epidural technique has many benefits, including rapid onset, superior first-stage analgesia, and the need for fewer supplemental doses when compared to a standard epidural. For these reasons, this technique is currently gaining in popularity. However, the combined spinal-epidural technique is also known to be associated with a risk of fetal bradycardia. The authors of this study attempted to determine whether the risk of this adverse outcome could be reduced by administering a prophylactic 10 mg dose of intravenous ephedrine. They also evaluated the rate of urgent cesarean delivery, the need for supplemental doses of ephedrine, maternal blood pressure, uterine hypertonus and tachysystole, as well as fetal heart rate patterns before and after the combined spinal-epidural.
Fostering the Development of Master Adaptive Learners: A Conceptual Model to Guide Skill Acquisition in Medical Education
Authors: Cutrer William B. , Miller Bonnie , Pusic Martin V. , Mejicano George , Mangrulkar Rajesh S. , Gruppen Larry D. , Hawkins Richard E. , Skochelak Susan E. , Moore Donald E.
Published: August 2016

Change is ubiquitous in health care, making continuous adaptation necessary for clinicians to provide the best possible care to their patients. The authors propose that developing the capabilities of a Master Adaptive Learner will provide future physicians with strategies for learning in the health care environment and for managing change more effectively. The concept of a Master Adaptive Learner describes a metacognitive approach to learning based on self-regulation that can foster the development and use of adaptive expertise in practice. The authors describe a conceptual literature-based model for a Master Adaptive Learner that provides a shared language to facilitate exploration and conversation about both successes and struggles during the learning process.
Recent Increases in the U.S. Maternal Mortality Rate
Authors: MacDorman Marian F. , Declercq Eugene , Cabral Howard , Morton Christine
Published: August 2016

OBJECTIVE:

To develop methods for trend analysis of vital statistics maternal mortality data, taking into account changes in pregnancy question formats over time and between states, and to provide an overview of U.S. maternal mortality trends from 2000 to 2014.

METHODS:

This observational study analyzed vital statistics maternal mortality data from all U.S. states in relation to the format and year of adoption of the pregnancy question. Correction factors were developed to adjust data from before the standard pregnancy question was adopted to promote accurate trend analysis. Joinpoint regression was used to analyze trends for groups of states with similar pregnancy questions.

RESULTS:

The estimated maternal mortality rate (per 100,000 live births) for 48 states and Washington, DC (excluding California and Texas, analyzed separately) increased by 26.6%, from 18.8 in 2000 to 23.8 in 2014. California showed a declining trend, whereas Texas had a sudden increase in 2011–2012. Analysis of the measurement change suggests that U.S. rates in the early 2000s were higher than previously reported.

CONCLUSION:

Despite the United Nations Millennium Development Goal for a 75% reduction in maternal mortality by 2015, the estimated maternal mortality rate for 48 states and Washington, DC, increased from 2000 to 2014; the international trend was in the opposite direction. There is a need to redouble efforts to prevent maternal deaths and improve maternity care for the 4 million U.S. women giving birth each year.
Atypical Endometrial Polyps and Concurrent Endometrial Cancer
Authors: de Rijk Simone R. , Steenbergen Marlie E. , Nieboer Theodoor E. , Coppus Sjors F.
Published: August 2016

OBJECTIVE:

To estimate the risk of concurrent endometrial cancer in nonpolypoid endometrium when atypia was diagnosed within an endometrial polyp.

DATA SOURCES:

MEDLINE, EMBASE, Web of Science, and ClinicalTrials.gov were searched for studies published between 1990 and January 2015 in which 1) women with atypical hyperplastic endometrial polyps underwent a consecutive hysterectomy; or 2) the natural behavior of endometrium with concurrent atypical endometrial polyps was evaluated.

METHODS OF STUDY SELECTION:

Studies were selected when at least one patient within each study was initially diagnosed with an atypical endometrial polyp for which follow-up pathology was available.

RESULTS:

Broad searches yielded 2,922 authentic citations, 307 met criteria for full-text evaluation, and 10 met inclusion criteria. Two authors independently reviewed articles and consensus was reached. The final selection included eight retrospective studies reporting on concurrent endometrial cancer in case of atypical endometrial polyps and two follow-up studies on patients conserving their uterus after hysteroscopic resection of atypical endometrial polyps. In total, 127 patients were included with an initial diagnosis of atypical endometrial hyperplasia within polyps. Meta-analysis showed a pooled risk estimate of 5.6% (95% confidence interval [CI] 0.2–17.6%) on concurrent endometrial cancer after resection of an atypical endometrial polyp.

CONCLUSION:

The pooled risk estimate of 5.6% (95% CI 0.2–17.6%) on endometrial cancer when atypia is found within an endometrial polyp differs from the well-established risk of nonpolypoid atypical endometrial hyperplasia on endometrial cancer of up to 42%. This risk of endometrial cancer is important in the process of shared decision-making regarding follow-up and further treatment.
Salpingo-oophorectomy at the Time of Benign Hysterectomy
Authors: Evans Elizabeth Casiano , Matteson Kristen A. , Orejuela Francisco J. , Alperin Marianna , Balk Ethan M. , El-Nashar Sherif , Gleason Jonathan L. , Grimes Cara , Jeppson Peter , Mathews Cara , Wheeler Thomas L. , Murphy Miles ,   for the Society of Gynecologic Surgeons Systematic Review Group
Published: August 2016

OBJECTIVE:

To compare the long-term risks associated with salpingo-oophorectomy with ovarian conservation at the time of benign hysterectomy.

DATA SOURCES:

MEDLINE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials were searched from inception to January 30, 2015. We included prospective and retrospective comparative studies of women with benign hysterectomy who had either bilateral salpingo-oophorectomy (BSO) or conservation of one or both ovaries.

METHODS OF STUDY SELECTION:

Reviewers double-screened 5,568 citations and extracted eligible studies into customized forms. Twenty-six comparative studies met inclusion criteria. Studies were assessed for results, quality, and strength of evidence.

TABULATION, INTEGRATION, AND RESULTS:

Studies were extracted for participant, intervention, comparator, and outcomes data. When compared with hysterectomy with BSO, prevalence of reoperation and ovarian cancer was higher in women with ovarian conservation (ovarian cancer risk of 0.14–0.7% compared with 0.02–0.04% among those with BSO). Hysterectomy with BSO was associated with a lower incidence of breast and total cancer, but no difference in the incidence of cancer mortality was found when compared with ovarian conservation. All-cause mortality was higher in women younger than age 45 years at the time of BSO who were not treated with estrogen replacement therapy (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.04–1.92). Coronary heart disease (HR 1.26, 95% CI 1.04–1.54) and cardiovascular death were higher among women with BSO (HR 1.84, 95% CI 1.27–2.68), especially women younger than 45 years who were not treated with estrogen. Finally, there was an increase in the prevalence of dementia and Parkinson disease among women with BSO compared with conservation, especially in women younger than age 50 years. Clinical practice guidelines were devised based on these results.

CONCLUSION:

Bilateral salpingo-oophorectomy offers the advantage of effectively eliminating the risk of ovarian cancer and reoperation but can be detrimental to other aspects of health, especially among women younger than age 45 years.
Recent advances in dermatomyositis-specific autoantibodies
Authors: Fujimoto Manabu , Watanabe Rei , Ishitsuka Yosuke , Okiyama Naoko
Published: August 2016

Purpose of review

In dermatomyositis, disease-specific autoantibodies now cover more than 70% of patients. These autoantibodies closely correlate with distinct clinical manifestations. In the past few years, extensive evidence has been accumulated on clinical significance of dermatomyositis-specific autoantibodies including autoantibodies against melanoma differentiation antigen 5 (MDA5), transcriptional intermediary factor 1 (TIF1), nuclear matrix protein 2 (NXP2), and small ubiquitin-like modifier activating enzyme (SAE).

Recent findings

Anti-MDA5 antibodies are found with high specificity in clinically amyopathic dermatomyositis presenting rapidly progressive interstitial lung disease (ILD) especially in Asian population. Similar tendency has been reported in the US/Europe, although the frequency of positivity and the type of ILD may differ. Anti-TIF1 antibodies are present in juvenile and adult dermatomyositis patients with close correlation with malignancy in adult population. Anti-NXP2 antibodies share similar phenotype with anti-TIF1 antibodies, except that anti-NXP2 antibodies are associated with calcinosis and severe muscle disease. Although numbers are still small, patients with anti-SAE antibodies tend to present skin disease first and then progress to muscle weakness with systematic symptoms including dysphagia. Moreover, distinct cutaneous manifestations and muscle histopathology findings for each autoantibody have been reported.

‘Autoantibody-based classification’ of dermatomyositis subsets is now a useful strategy for comprehending the heterogeneous spectrum of dermatomyositis.
Animal models of scleroderma: recent progress
Authors: Marangoni Roberta G. , Varga John , Tourtellotte Warren G.
Published: August 2016

Purpose of review

We discuss recent advances in evaluating and optimizing animal models of systemic sclerosis (SSc). Such models could be of value for illuminating etiopathogenesis using hypothesis-testing experimental approaches, for developing effective disease-modifying therapies, and for uncovering clinically relevant biomarkers.

Recent findings

We describe recent advances in previously reported and novel animal models of SSc. The limitations of each animal model and their ability to recapitulate the pathophysiology of recognized molecular subsets of SSc are discussed. We highlight attrition of dermal white adipose tissue as a consistent pathological feature of dermal fibrosis in mouse models, and its relevance to SSc-associated cutaneous fibrosis.

Several animal models potentially useful for studying SSc pathogenesis have been described. Recent studies highlight particular strengths and weaknesses of selected models in recapitulating distinct features of the human disease. When used in the appropriate experimental setting, and in combination, these models singly and together provide a powerful set of in-vivo tools to define underlying mechanisms of disease and to develop and evaluate effective antifibrotic therapies.
Scoliosis in Down’s syndrome
Authors: Abousamra Oussama , Duque Orozco Maria del Pilar , Er Mehmet S. , Rogers Kenneth J. , Sees Julieanne P. , Miller Freeman
Published: August 2016

This study reports the recent experience in the management of scoliosis in Down’s syndrome. Curve patterns, progression in brace, and surgical outcomes were recorded. Cardiac surgery history was compared between children with and without scoliosis. Out of 581 children with Down’s syndrome, 62 children had scoliosis. The mean age of the children was 13.8 years. The mean magnitude was 31°. Bracing was successful in five of seven patients. Ten children had posterior spinal fusion with follow-up of 2.6 years (1–7.3). One deep wound infection was recorded with no revision. No difference was found in cardiac surgery history between children with and without scoliosis. Level of Evidence: Type IV – prognostic and therapeutic study.
Defining Futile and Potentially Inappropriate Interventions: A Policy Statement From the Society of Critical Care Medicine Ethics Committee
Authors: Kon Alexander A. , Shepard Eric K. , Sederstrom Nneka O. , Swoboda Sandra M. , Marshall Mary Faith , Birriel Barbara , Rincon Fred
Published: August 2016

Objectives:

The Society of Critical Care Medicine and four other major critical care organizations have endorsed a seven-step process to resolve disagreements about potentially inappropriate treatments. The multiorganization statement (entitled: An official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units) provides examples of potentially inappropriate treatments; however, no clear definition is provided. This statement was developed to provide a clear definition of inappropriate interventions in the ICU environment.

Design:

A subcommittee of the Society of Critical Care Medicine Ethics Committee performed a systematic review of empirical research published in peer-reviewed journals as well as professional organization position statements to generate recommendations. Recommendations approved by consensus of the full Society of Critical Care Medicine Ethics Committees and the Society of Critical Care Medicine Council were included in the statement.

Measurements and Main Results:

ICU interventions should generally be considered inappropriate when there is no reasonable expectation that the patient will improve sufficiently to survive outside the acute care setting, or when there is no reasonable expectation that the patient’s neurologic function will improve sufficiently to allow the patient to perceive the benefits of treatment. This definition should not be considered exhaustive; there will be cases in which life-prolonging interventions may reasonably be considered inappropriate even when the patient would survive outside the acute care setting with sufficient cognitive ability to perceive the benefits of treatment. When patients or surrogate decision makers demand interventions that the clinician believes are potentially inappropriate, the seven-step process presented in the multiorganization statement should be followed. Clinicians should recognize the limits of prognostication when evaluating potential neurologic outcome and terminal cases. At times, it may be appropriate to provide time-limited ICU interventions to patients if doing so furthers the patient’s reasonable goals of care. If the patient is experiencing pain or suffering, treatment to relieve pain and suffering is always appropriate.

Conclusions:

The Society of Critical Care Medicine supports the seven-step process presented in the multiorganization statement. This statement provides added guidance to clinicians in the ICU environment.
Development and Validation of a Score to Predict Mortality in Children Undergoing Extracorporeal Membrane Oxygenation for Respiratory Failure: Pediatric Pulmonary Rescue With Extracorporeal Membrane Oxygenation Prediction Score*
Authors: Bailly David K. , Reeder Ron W. , Zabrocki Luke A. , Hubbard Anna M. , Wilkes Jacob , Bratton Susan L. , Thiagarajan Ravi R.
Published: August 2016

Objective:

Our objective was to develop and validate a prognostic score for predicting mortality at the time of extracorporeal membrane oxygenation initiation for children with respiratory failure. Preextracorporeal membrane oxygenation mortality prediction is important for determining center-specific risk-adjusted outcomes and counseling families.

Design:

Multivariable logistic regression of a large international cohort of pediatric extracorporeal membrane oxygenation patients.

Setting:

Multi-institutional data.

Patients:

Prognostic score development: A total of 4,352 children more than 7 days to less than 18 years old, with an initial extracorporeal membrane oxygenation run for respiratory failure reported to the Extracorporeal Life Support Organization’s data registry during 2001–2013 were used for derivation (70%) and validation (30%). Bidirectional stepwise logistic regression was used to identify factors associated with mortality. Retained variables were assigned a score based on the odds of mortality with higher scores indicating greater mortality. External validation was accomplished using 2,007 patients from the Pediatric Health Information System dataset.

Interventions:

None.

Measurements and Main Results:

The Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction score included mode of extracorporeal membrane oxygenation; preextracorporeal membrane oxygenation mechanical ventilation more than 14 days; preextracorporeal membrane oxygenation severity of hypoxia; primary pulmonary diagnostic categories including, asthma, aspiration, respiratory syncytial virus, sepsis-induced respiratory failure, pertussis, and “other”; and preextracorporeal membrane oxygenation comorbid conditions of cardiac arrest, cancer, renal and liver dysfunction. The area under the receiver operating characteristic curve for internal and external validation datasets were 0.69 (95% CI, 0.67–0.71) and 0.66 (95% CI, 0.63–0.69).

Conclusions:

Pediatric Pulmonary Rescue with Extracorporeal Membrane Oxygenation Prediction is a validated tool for predicting in-hospital mortality among children with respiratory failure receiving extracorporeal membrane oxygenation support.
Use of Sleep Evaluations and Treatments in Children with Down Syndrome
Authors: Esbensen Anna J. , Beebe Dean W. , Byars Kelly C. , Hoffman Emily K.
Published: August 2016

Objective:

To characterize practice patterns regarding sleep evaluation and intervention among children with Down syndrome (DS).

Method:

Data were obtained from electronic health records from 2009 to 2013 for a retrospective cohort of 954 children with DS, aged 5 to 21 years during the time sampled. International Classification of Diseases, Ninth Revision, diagnoses were used to identify children with obstructive sleep apnea and/or behavioral sleep disturbances. Primary outcomes were confirmed by participation in an overnight diagnostic polysomnography (PSG) and/or documented provision of specified sleep interventions including positive airway pressure, otolaryngology (ENT) surgery, sleep medication, and behavioral sleep therapy.

Results:

Overall, 47.7% of children with DS had undergone PSG, 39.1% had diagnosed sleep problems, and of those diagnosed with sleep problems, 81.2% had received sleep intervention. Consistent with best practice clinical care, sleep treatments matched the diagnosed sleep problems. Age, gender, and race, but not body mass index (BMI), were associated with PSG completion rate and occurrence rates for ENT surgery and sleep medication usage. BMI was associated with obstructive sleep apnea.

Conclusion:

Despite high rates of reported sleep problems in children with DS, less than half underwent PSG. Children diagnosed with sleep problems received treatment consistent with their sleep diagnosis. However, age and gender were associated with differential rates of treatment delivery that was incongruous with prevalence rates for diagnosed sleep problems. These findings underscore the importance of screening for sleep problems in children with DS, and referring for and providing appropriate targeted sleep interventions.
CLINICALLY INVISIBLE RETINAL HEMANGIOBLASTOMAS DETECTED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY AND FLUORESCEIN ANGIOGRAPHY IN TWINS
Authors: Schoen Marisa A. , Shields Carol L. , Say Emil Anthony T. , Douglass Alexzandra M. , Shields Jerry A. , Jampol Lee M.
Published: August 2016

Purpose:

To report subclinical retinal hemangioblastoma detected by enhanced depth imaging optical coherence tomography and fluorescein angiography in at-risk twins.

Methods:

Case report.

Results:

A set of twins, age 7 years, (Twin A and Twin B) with known family history of von Hippel–Lindau disease (gene test positive) and no systemic manifestations were evaluated. Visual acuity was 20/20 in both eyes of both twins. Anterior segment examination and intraocular pressures were unremarkable in both eyes. Twin A showed no clinically visible tumor in the right eye, and a clinically evident 4-mm hemangioblastoma in the superior retina of the left eye. The enhanced depth imaging optical coherence tomography demonstrated normal fovea in both eyes. However, imaging at the inferonasal juxtapapillary region in the right eye documented an intraretinal mass from nerve fiber layer to outer plexiform layer on enhanced depth imaging optical coherence tomography and with hyperfluorescence on fluorescein angiography, consistent with retinal hemangioblastoma. Twin B demonstrated no clinically visible tumors in both eyes, but the left eye showed a small hyperreflective lesion in the parafoveal region on spectral domain optical coherence tomography from inner to outer nuclear layers, with no cystoid changes or subretinal fluid. The lesion was slightly hyperfluorescent on fluorescein angiography, consistent with hemangioblastoma. The optical coherence tomography angiography showed no vascularity within the lesion. Twin A was treated with laser photocoagulation to the larger hemangioblastoma in the left eye, and the asymptomatic juxtapapillary tumor was observed. Twin B was managed with cautious observation as treatment to the left eye could lead to vision loss.

Conclusion:

Patients at risk for retinal hemangioblastoma should have routine imaging with fundus photography, fluorescein angiography, and enhanced depth imaging optical coherence tomography for subclinical detection of asymptomatic tumors.
International Expert Consensus on Sutureless and Rapid Deployment Valves in Aortic Valve Replacement Using Minimally Invasive Approaches
Authors: Glauber Mattia , Moten Simon C. , Quaini Eugenio , Solinas Marco , Folliguet Thierry A. , Meuris Bart , Miceli Antonio , Oberwalder Peter J. , Rambaldini Manfredo , Teoh Kevin H. T. , Bhatnagar Gopal , Borger Michael A. , Bouchard Denis , Bouchot Olivier , Clark Stephen C. , Dapunt Otto E. , Ferrarini Matteo , Fischlein Theodor J. M. , Laufer Guenther , Mignosa Carmelo , Millner Russell , Noirhomme Philippe , Pfeiffer Steffen , Ruyra-Baliarda Xavier , Shrestha Malakh Lal , Suri Rakesh M. , Troise Giovanni , Gersak Borut
Published: August 2016

Objective

To define the benefit of sutureless and rapid deployment valves in current minimally invasive approaches in isolated aortic valve replacement.

Methods

A panel of 28 international experts with expertise in both minimally invasive aortic valve replacement and rapid deployment valves was constituted. After thorough literature review, the experts rated evidence-based recommendations in a modified Delphi approach.

Results

No guideline could be retrieved. Thirty-three clinical trials and 9 systematic reviews could be identified for detailed text analysis to obtain a total of 24 recommendations. After rating by the experts 12, final recommendations were identified: preoperative computed to-mographic scan as well as intraoperative transesophageal echocardiography are highly recommended. Suitable annular sizes are 19 to 27 mm. There is a contraindication for bicuspid valves only for type 0 and for annular abscess or destruction due to infective endocarditis. The use of sutureless and rapid deployment valves reduces extracorporeal circulation and aortic cross-clamp time and leads to less early complications as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions, paravalvular leakages and aortic regurgitation, and renal replacement therapy, respectively. These clinical outcomes result in reduced intensive care unit and hospital stay and reduced costs. The use of sutureless and rapid deployment valves will lead to a higher adoption rate of minimally invasive approaches in aortic valve replacement. Respect should be taken to a necessary short learning curve for both sutureless and minimally invasive programs.

Conclusions

Sutureless and rapid deployment aortic valve replacement together with minimally invasive approaches offers an attractive option in aortic valve placement for patients requiring biological valve replacement.
Assessment of Drug-Associated Extrapyramidal Symptoms in People With Intellectual Disability
Authors: de Kuijper Gerda M. , Hoekstra Pieter J.
Published: August 2016

Drug-associated extrapyramidal symptoms (EPS) in people with intellectual disability (ID) may be difficult to recognize, and clinicians' assessments may be hampered by lack of patients' capacities to adequately cooperate and by lack of reliable instruments to measure EPS in this population. Therefore, we compared assessments based on professional caregivers' observations with the informant-based validated Matson Evaluation of Drug Side Effects (MEDS) scale with assessments by clinicians using a set of clinical rating scales, most of which have not been validated for use in this population. We also compared 2 dyskinesia scales by replacing the widely used but not validated Abnormal Involuntary Movement Scale with the validated Dyskinesia Identification System Condensed User Scale (DISCUS) in half of the set of scales. We used linear regression to analyze associations between EPS as measured with MEDS and EPS as measured with the sets of scales at item and at scale level.

Of the 30 MEDS items, 6 were associated with items of the other scales. At scale level, we found no significant associations. Comparison of the Abnormal Involuntary Movement Scale with the DISCUS indicated that the DISCUS may be preferable for use in people with ID.

Results may be explained by shortcomings in education and training of caregivers and by lack of reliable assessments and rating scales for EPS in people with ID.

We conclude that there is an urgent need for education and training of care professionals and clinicians in this area and for studies investigating the psychometric properties of rating scales.
Stakeholders’ Perspectives on Stakeholder-engaged Research (SER)
Authors: Mackie Thomas I. , Sheldrick Radley C. , de Ferranti Sarah D. , Saunders Tully , Rojas Erick G. , Leslie Laurel K.
Published: August 2016

Background:

US federal funding agencies increasingly incentivize stakeholder-engaged research which represents a paradigm shift toward incorporating a range of stakeholders in research design, conduct, and dissemination.

Objectives:

We use qualitative methods to capture experience-based recommendations on how to operationalize 4 Patient-Centered Outcomes Research (PCOR) principles in stakeholder-engaged research, specifically: (1) reciprocal relationships; (2) colearning; (3) partnership; and (4) trust, transparency, and honesty.

Research Design:

We conducted semistructured interviews with members of a stakeholder panel who participated in a 2-year comparative effectiveness study of cholesterol screening and treatment among young adults.

Sample:

Participants included 8 young adults and parent panelists and 11 professional panelists (clinicians, researchers, policy developers, and disseminators).

Measures:

The interview guide included questions about the 4 PCOR principles and queried preferred strategies to attain them. Interview transcripts were analyzed using an a priori and emergent coding structure.

Results:

Participants provided strategies to promote the 4 PCOR principles. Although some stakeholder-identified strategies were complementary, others conflicted due to (1) competing ideologies identified among the principles, and (2) distinct stakeholder preferences. Illustrative of competing ideologies, participants simultaneously preferred receiving relevant articles before calls (to facilitate colearning) but also minimal outside reading (to achieve partnership). Illustrative of distinct stakeholder preferences, young adult and parent panelists generally preferred calls to occur on weekends/evenings, whereas professional panelists preferred mid-week work hours.

Conclusions:

Our exploratory study provides stakeholder-identified strategies to achieve the 4 PCOR principles, and demonstrates the need to identify, acknowledge, and address potentially conflicting strategies due to the potential for competing ideologies or variation in stakeholder preferences.
Hospital Variation and Patient Characteristics Associated With Vena Cava Filter Utilization
Authors: Brown Joshua D. , Talbert Jeffery C.
Published: August 2016

Introduction:

There is a wide variation in the use of vena cava filter (VCF).

Objective:

This study assessed the hospital and patient characteristics associated with VCF use in deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods:

Inpatient discharge data from all acute care hospitals with DVT/PE during 2008–2014 in Kentucky were used. Hierarchical logistic regression models were used to evaluate the relationships of study variables with VCF use.

Results:

During the study period, 81,922 discharges for DVT/PE were observed and 10.5% of these received a VCF. This included 12,083 cases of PE+DVT, 18,571 cases of PE only, and 51,268 cases of DVT only. VCF use among these groups was 22.7%, 6.0%, and 7.8%, respectively. In adjusted analyses, VCF use was associated with increasing age, indicating that those over age 65 were twice as likely to receive a filter compared with the reference (21–25 y old) group. Significant comorbidities associated with VCF use included cancer, liver disease, cerebrovascular disease, atrial fibrillation, anemia, and concurrent bleeding. Lower extremity, proximal DVTs, and patients receiving thrombolytic therapy or embolectomy, those having surgery, and those who were unstable or had trauma, were also more likely to receive a filter. Among cancer types, brain and metastatic tumors were significantly associated with VCF use. Between-hospital variation after controlling for all covariates was 7.1%.

Conclusions:

There was high variation in the use of VCFs. Several high-risk subgroups were more likely to use VCFs including older adults and those with cancer and concurrent bleeding.
The Effects of Medicaid Home and Community-based Services Waivers on Unmet Needs Among Children With Autism Spectrum Disorder
Authors: Leslie Douglas L. , Iskandarani Khaled , Dick Andrew W. , Mandell David S. , Yu Hao , Velott Diana , Agbese Edeanya , Stein Bradley D.
Published: August 2016

Background:

Several states have passed Medicaid Home and Community-based Services (HCBS) waivers that expand eligibility criteria and available services for children with autism spectrum disorder (ASD). Previous research has shown considerable variation in these waivers, but little is known about the extent to which they address the health care needs of children with ASD.

Objective:

To determine the effects of Medicaid HCBS waivers, and their characteristics, on unmet health care needs among children with ASD.

Methods:

We used data from the 2003, 2007, and 2011 waves of the National Survey of Children’s Health with detailed information on the Medicaid HCBS waiver programs of 35 states. Quasi-difference-in-difference-in-differences models were used to determine the effects of waivers and their characteristics on parent report of unmet health care needs of children with ASD compared with children without ASD.

Results:

Greater waiver cost limits per child, estimated costs of services, and enrollment limits were associated with significant decreases in the adjusted rate of unmet health care needs, with considerable variation by household income level.

Conclusions:

These findings suggest that Medicaid HCBS waivers significantly decrease the unmet need for health care among children with ASD, most substantially among those who would not otherwise qualify for Medicaid. The findings regarding the effects of specific aspects of these waivers can inform the development of insurance policies in other states to address the needs of children with ASD.
Evaluation of Proteinuria in β-Thalassemia Major Patients With and Without Diabetes Mellitus Taking Deferasirox
Authors: Karimi Mehran , Avazpour Abbas , Haghpanah Sezaneh , Toosi Foroogh , Badie Arash
Published: August 2016

Background:

β-thalassemia is the most common heredity disease in Iran. Regular blood transfusion is critical to sustain life and normal growth. Deferasirox is an oral chelator. One of the side effects of the deferasirox is proteinuria.

Objectives:

This study aimed to investigate the safety of deferasirox on kidney function in diabetic and nondiabetic β-thalassemia major patients.

Materials and Methods:

In this cross-sectional study, 34 diabetic and 36 nondiabetic patients who take deferasirox (Exjade) 20 to 40 mg/kg/d were studied. Exclusion criteria included patient with renal failure, proteinuria, hepatitis B, hepatitis C, and the patients who refused to continue the study to the end. Subjects were divided into diabetic and nondiabetic groups. Spot urine protein/creatinine ratio, urinary analysis, alanine transaminase, aspartate transaminase, creatinine, fasting blood sugar, blood urea nitrogen, and serum ferritin were checked every 3 months. Patients were followed for a period of 1 year.

Results:

In the ninth month after therapy there was a significant relationship in mean change of spot urine protein/creatinine ratio between diabetic and nondiabetic (P=0.011). Spot urine protein/creatinine ratio in diabetic and nondiabetic group was 0.19±0.18 and 0.1±0.05, respectively, which showed no significant relationship between the 2 groups at the end of study (P=0.162).

Conclusion:

The results of our study showed that consumption of deferasirox is safe, as there was no significant relationship between spot urine protein/creatinine ratio in diabetic and nondiabetic group. Deferasirox consumption is not associated with increased proteinuria in diabetic patients compared with nondiabetic group having only a transient proteinuria.
Multitype Infections With Human Papillomavirus: Impact of Human Immunodeficiency Virus Coinfection
Authors: Massad Leslie , Keller Marla , Xie Xianhong , Minkoff Howard , Palefsky Joel , D'Souza Gypsyamber , Colie Christine , Villacres Maria , Strickler Howard
Published: August 2016

Background

Human immunodeficiency virus (HIV) infection predisposes women to genital coinfection with human papillomaviruses (HPVs). Concurrent infection with multiple HPV types has been documented, but its frequency, correlates, and impact on development of precancer are poorly defined in HIV-seropositive women.

Methods

Human immunodeficiency virus-seropositive women and -seronegative comparison women were enrolled in a cohort study and followed every 6 months from 1994 to 2006. Cervicovaginal lavage samples were tested for HPV types using polymerase chain reaction amplification with MY09/MY11 consensus primers followed by hybridization with consensus and HPV type-specific probes. Analyses were performed using generalized estimating equations.

Results

Multitype HPV infections were found in 594 (23%) of 2543 HIV-seropositive women and 49 (5%) of 895 HIV-seronegative women (P < 0.0001). Compared with HPV uninfected women, those with multiple concurrent HPV infections were more likely to be younger, nonwhite, and current smokers, with lower CD4 counts and HIV RNA levels. The average proportion of women with multitype HPV infections across visits was 21% in HIV-seropositive women and 3% in HIV-seronegative women (P <0.0001). Compared with infection with 1 oncogenic HPV type, multitype concurrent infection with at least 1 other HPV type at baseline did not measurably increase the risk of ever having cervical intraepithelial neoplasia 3+ detected during follow-up (odds ratio, 0.80; 95% confidence interval, 0.32–2.03, P = 0.65).

Conclusions

Concurrent multitype HPV infection is common in HIV-seropositive women and frequency rises as CD4 count declines, but multitype infection does not increase precancer risk.
Mixed Mesonephric Adenocarcinoma and High-grade Neuroendocrine Carcinoma of the Uterine Cervix: Case Description of a Previously Unreported Entity With Insights Into Its Molecular Pathogenesis
Authors: Cavalcanti Marcela S. , Schultheis Anne M. , Ho Caleb , Wang Lu , DeLair Deborah F. , Weigelt Britta , Gardner Ginger , Lichtman Stuart M. , Hameed Meera , Park Kay J.
Published: August 2016

Human papillomavirus (HPV)-negative cervical carcinomas are uncommon and typically encompass unusual histologic subtypes. Mesonephric adenocarcinoma is one such subtype. Mesonephric tumors in the female genital tract are thought to arise from Wolffian remnants, and are extremely rare tumors with widely variable morphology. Sarcomatoid dedifferentiation has been previously described in a few cases, but other forms of dedifferentiation have not been reported. Neuroendocrine carcinoma of the cervix (e.g. small cell carcinoma) is associated with HPV infection, typically HPV 18. These tumors often arise in association with a conventional epithelial component such as squamous cell carcinoma or usual-type endocervical adenocarcinoma. We describe a case of mesonephric adenocarcinoma of the uterine cervix associated with an HPV-negative high-grade neuroendocrine carcinoma at the morphologic and immunophenotypic level, for which we performed targeted massively parallel sequencing analysis of the 2 elements. Both components shared identical mutations in U2AF1 p.R156H (c.467G>A) and GATA3 p.M422fs (c.1263dupG), as well as MYCN amplification. In addition, the neuroendocrine carcinoma harbored TP53 and MST1R mutations not present in the mesonephric carcinoma. Our data suggest a clonal origin of the 2 components of this rare entity, rather than a collision tumor.