bluuebunny/crossref_metadata_2025_split huggingface dataset:
OncoSimulR: genetic simulation with arbitrary epistasis and mutator genes in asexual populations
Authors: Diaz-Uriarte Ramon 
Published: February 2017

Abstract

Summary
OncoSimulR implements forward-time genetic simulations of biallelic loci in asexual populations with special focus on cancer progression. Fitness can be defined as an arbitrary function of genetic interactions between multiple genes or modules of genes, including epistasis, restrictions in the order of accumulation of mutations, and order effects. Mutation rates can differ among genes, and can be affected by (anti)mutator genes. Also available are sampling from simulations (including single-cell sampling), plotting the genealogical relationships of clones and generating and plotting fitness landscapes.

Availability and Implementation
Implemented in R and C ++, freely available from BioConductor for Linux, Mac and Windows under the GNU GPL license. Version 2.5.9 or higher available from: http://www.bioconductor.org/packages/devel/bioc/html/OncoSimulR.html. GitHub repository at: https://github.com/rdiaz02/OncoSimul

Supplementary information
Supplementary data are available at Bioinformatics online.
The Association Between Geographic Density of Infectious Disease Physicians and Limb Preservation in Patients With Diabetic Foot Ulcers
Authors: Brennan Meghan B. , Allen Glenn O. , Ferguson Patrick D. , McBride Joseph A. , Crnich Christopher J. , Smith Maureen A. 
Published: February 2017

Abstract

Background
Avoiding major (above-ankle) amputation in patients with diabetic foot ulcers is best accomplished by multidisciplinary care teams with access to infectious disease specialists. However, access to infectious disease physicians is partially influenced by geography. We assessed the effect of living in a hospital referral region with a high geographic density of infectious disease physicians on major amputation for patients with diabetic foot ulcers. We studied geographic density, rather than infectious disease consultation, to capture both the direct and indirect (eg, informal consultation) effects of access to these providers on major amputation.

Methods
We used a national retrospective cohort of 56440 Medicare enrollees with incident diabetic foot ulcers. Cox proportional hazard models were used to assess the relationship between infectious disease physician density and major amputation, while controlling for patient demographics, comorbidities, and ulcer severity.

Results
Living in hospital referral regions with high geographic density of infectious disease physicians was associated with a reduced risk of major amputation after controlling for demographics, comorbidities, and ulcer severity (hazard ratio, .83; 95% confidence interval, .75–.91; P &lt; .001). The relationship between the geographic density of infectious disease physicians and major amputation was not different based on ulcer severity and was maintained when adjusting for socioeconomic factors and modeling amputation-free survival.

Conclusions
Infectious disease physicians may play an important role in limb salvage. Future studies should explore whether improved access to infectious disease physicians results in fewer major amputations.
Community Environmental Contamination of Toxigenic Clostridium difficile
Authors: Alam M Jahangir , Walk Seth T. , Endres Bradley T. , Basseres Eugenie , Khaleduzzaman Mohammed , Amadio Jonathan , Musick William L. , Christensen Jennifer L. , Kuo Julie , Atmar Robert L. , Garey Kevin W. 
Published: February 2017

Abstract

Background
Clostridium difficile infection is often considered to result from recent acquisition of a C difficile isolate in a healthcare setting. However, C difficile spores can persist for long periods of time, suggesting a potentially large community environmental reservoir. The objectives of this study were to assess community environmental contamination of toxigenic C difficile and to assess strain distribution in environmental versus clinical isolates.

Methods
From 2013 to 2015, we collected community environmental swabs from homes and public areas in Houston, Texas to assess C difficile contamination. All positive isolates were tested for C difficile toxins A and B, ribotyped, and compared with clinical C difficile isolates obtained from hospitalized patients in Houston healthcare settings.

Results
A total of 2538 environmental samples were collected over the study period. These included samples obtained from homes (n = 1079), parks (n = 491), chain stores (n = 225), fast food restaurants (n = 123), other commercial stores (n = 172), and hospitals (n = 448). Overall, 418 environmental isolates grew toxigenic C difficile (16.5%; P &lt; .001) most commonly from parks (24.6%), followed by homes (17.1%), hospitals (16.5%), commercial stores (8.1%), chain stores (7.6%), and fast food restaurants (6.5%). A similar distribution of ribotypes was observed between clinical and environmental isolates with the exception that ribotype 027 was more common in clinical isolates compared with environmental isolates (P &lt; .001).

Conclusions
We identified a high prevalence of toxigenic C difficile from community environs that were similar ribotypes to clinical isolates. These findings suggest that interventions beyond isolation of symptomatic patients should be targeted for prevention of C difficile infection.
Influence of Ethanol on Oxycodone-induced Respiratory Depression
Authors: van der Schrier Rutger , Roozekrans Margot , Olofsen Erik , Aarts Leon , van Velzen Monique , de Jong Merijn , Dahan Albert , Niesters Marieke 
Published: February 2017

Abstract

Background
Respiratory depression is a potentially fatal complication of opioid use, which may be exacerbated by simultaneous ethanol intake. In this three-way sequential crossover dose-escalating study, the influence of coadministration of oral oxycodone and intravenous ethanol was assessed on resting ventilation, apneic events and the hypercapnic ventilatory response in healthy young and older volunteers.

Methods
Twelve young (21 to 28 yr) and 12 elderly (66 to 77 yr) opioid-naive participants ingested one 20 mg oxycodone tablet combined with an intravenous infusion of 0, 0.5, or 1 g/l ethanol. Resting respiratory variables and the primary outcome, minute ventilation at isohypercapnia (end-tidal partial pressure of carbon dioxide of 55 mmHg or VE55), were obtained at regular intervals during treatment.

Results
Oxycodone reduced baseline minute ventilation by 28% (P < 0.001 vs. control). Ethanol caused a further decrease of oxycodone-induced respiratory depression by another 19% at 1 g/l ethanol plus oxycodone (P < 0.01 vs. oxycodone). Ethanol combined with oxycodone caused a significant increase in the number of apneic events measured in a 6-min window with a median (range) increase from 1 (0 to 3) at 0 g/l ethanol to 1 (0 to 11) at 1 g/l ethanol (P < 0.01). Mean (95% CI) VE55 decreased from 33.4 (27.9 to 39.0) l/min (control) to 18.6 (15.6 to 21.6) l/min (oxycodone, P < 0.01 vs. control) and to 15.7 (12.7 to 18.6) l/min (oxycodone combined with ethanol, 1 g/l; P < 0.01 vs. oxycodone).

Conclusions
Ethanol together with oxycodone causes greater ventilatory depression than either alone, the magnitude of which is clinically relevant. Elderly participants were more affected than younger volunteers.
Association of the Hospital Volume of Frail Surgical Patients Cared for with Outcomes after Elective, Major Noncardiac Surgery
Authors: McIsaac Daniel I. , Wijeysundera Duminda N. , Huang Allen , Bryson Gregory L. , van Walraven Carl 
Published: February 2017

Abstract

Background
Frailty is a risk factor for adverse postoperative outcomes. Hospitals that perform higher volumes of surgery have better outcomes than low-volume providers. We hypothesized that frail patients undergoing elective surgery at hospitals that cared for a higher volume of similarly frail patients would have improved outcomes.

Methods
We conducted a retrospective, population-based cohort study using linked administrative data in Ontario, Canada. We identified all adult major, elective noncardiac surgery patients who were frail according to the validated Johns Hopkins Adjusted Clinical Groups (ACG®) frailty-defining diagnoses indicator. Hospitals were categorized into frailty volume quintiles based on volumes of frail surgical patients cared for. Multilevel, multivariable modeling measured the association of frailty volume with 30-day survival (primary outcome), complications, failure to rescue (secondary outcomes), and costs (tertiary outcome).

Results
Of 63,381 frail patients, 708 (1.1%) died after surgery. The thirty-day mortality rate in the lowest volume quintile was 1.1% compared to 0.9% in the highest. After adjustment for surgical risk, demographic characteristics, comorbidities, and clustering within hospitals, we found a significant association between frailty volume and improved survival (highest volume vs. lowest volume quintile: hazard ratio 0.51; 95% CI, 0.35 to 0.74; P < 0.0001). Although complication rates did not vary significantly between hospitals, failure-to-rescue rates were inversely related to volume.

Conclusions
Frail patients have reduced survival and increased failure to rescue when they undergo operations at hospitals having a lower volume of frail surgical patients. Concentration of perioperative care in centers that frequently treat high-risk frail patients could improve population outcomes.
Predictors of Hospital Readmission and Surgical Site Infection in the United States, Denmark, and Japan
Authors: Glassman Steven , Carreon Leah Y. , Andersen Mikkel , Asher Anthony , Eiskjær Soren , Gehrchen Martin , Imagama Shiro , Ishii Ken , Kaito Takahashi , Matsuyama Yukihiro , Moridaira Hiroshi , Mummaneni Praveen , Shaffrey Christopher , Matsumoto Morio 
Published: February 2017

Study Design.
Retrospective review of three spine surgery databases.

Objectives.
The purpose of the present study is to determine whether predictors of hospital readmission and surgical site infection (SSI) after lumbar fusion will be the same in United States, Denmark, and Japan.

Summary of Background Data.
Because clinical decision making becomes more data driven, risk stratification will be crucial to minimize complications. Spine surgeons worldwide face this issue, leading to parallel efforts to address risk stratification. This raises the question as to whether pooled data would be valuable and whether models generated in one country would be applicable to other populations.

Methods.
Predictors of SSI and 30-day readmission from three prospective databases (National Neurosurgery Quality and Outcomes Database [N2QOD] N = 2653, DaneSpine N = 1993, Japan Multicenter Spine Database [JAMSD] N = 3798) were determined and compared to identify common or divergent predictive risks.

Results.
Predictive variables differed in the three databases, for both readmission and SSI. Factors predictive for hospital readmission were American Society of Anesthesiologists (ASA) grade in N2QOD (P = 0.013, odds ratio [OR] 2.08), fusion levels in DaneSpine (P = 0.005, OR 1.67), and sex in JAMSD (P = 0.001, OR = 2.81). Associated differences in demographics and procedural factors included mean ASA grade (N2QOD = 2.45, JAMSD = 1.72) and fusion levels (N2QOD = 1.39, DaneSpine = 1.52, JAMSD = 1.34). For SSI, sex (P = 0.000, OR = 3.30), diabetes (P = 0.000, OR = 2.90), and length of stay (P = 0.000, OR = 1.02) were predictive in JAMSD. No predictors were identified in N2QOD or DaneSpine.

Conclusion.
Predictors of SSI and hospital readmission differ in the United States, Denmark, and Japan, suggesting that risk stratification models may need to be population specific or adjusted. Some differences in measured parameters exist in the three databases analyzed; however, patient and procedure selection also appear to differ and may limit the ability to directly pool data from different regions. Therefore, risk stratification models developed in one country may not be directly applicable to other countries.

Level of Evidence: 2
Generalized Leishmanides in an Immunodeprived Man
Authors: Fernandez-Flores Angel , Boada Aram , Fernández-Figueras Maria T. 
Published: February 2017

Abstract:
Leishmanides have been rarely reported in the literature. In this study, the authors present a case of a 50-year-old HIV-positive man who developed a generalized cutaneous eruption of papules and plaques in which no microorganism was demonstrated by culture, microscopical examination, immunohistochemistry, or polymerase chain reaction. The patient was eventually diagnosed with laryngeal leishmaniasis, and when treated, the cutaneous lesions greatly improved.
Combined Jessner Solution and Trichloroacetic Acid Versus Trichloroacetic Acid Alone in the Treatment of Melasma in Dark-Skinned Patients
Authors: Abdel-Meguid Azza M. , Taha Emad A. , Ismail Sahar A. 
Published: February 2017

BACKGROUND
Melasma is a common challenging pigmentary skin disorder especially in dark-skinned females urging them to seek medical help. Many modalities of treatment are available, but none is satisfactory.

OBJECTIVE
To compare safety and efficacy of combined trichloroacetic acid (TCA) (20%–25%) and Jessner's solution versus TCA (20%–25%) alone in dark patients with melasma.

MATERIALS AND METHODS
The study design was a split face, right-left, assessor-blinded, randomized controlled study. Twenty-four adult female patients (skin phototypes IV–V) with bilateral melasma were treated for 6 sessions at 2 weeks intervals. Clinical assessment of the 2 sides of the face with Melasma Area and Severity Index (MASI) score was performed, and photographs were taken before and after the peeling course.

RESULTS
Both therapeutic modalities showed significant decrease in MASI score, which was significantly lower on the side treated with both Jessner solution and TCA. There were significant negative correlations between the percentage of improvement of MASI score and both age of the patients and duration of the melasma.

CONCLUSION
Dark skin melasma can be treated with both regimens safely and effectively; however, combined Jessner solution and TCA is more effective.
High Frequency of Bone Marrow Depression During Congenital Toxoplasmosis Therapy in a Cohort of Children Identified by Neonatal Screening in Minas Gerais, Brazil
Authors: Carellos Ericka Viana Machado , de Andrade Juliana Queiroz , Romanelli Roberta Maia Castro , Tibúrcio Jacqueline Domingos , Januário José Nélio , Vasconcelos-Santos Daniel Vítor , Figueiredo Rosângela Maria , de Andrade Gláucia Manzan Queiroz 
Published: February 2017

Background:
There are few studies reporting frequency and control of adverse events associated with congenital toxoplasmosis treatment. The objective of this study is to describe treatment adherence and adverse hematologic events in a cohort of children identified with congenital toxoplasmosis in Minas Gerais, Brazil.

Methods:
Children were treated with sulfadiazine, pyrimethamine and folinic acid and were evaluated clinically and by laboratory tests at regular intervals.

Results:
Of 146,307 live newborns who participated in the Neonatal Screening Program in Minas Gerais in 2006–2007, 190 had congenital toxoplasmosis. Among the 171 children whose treatment data were available, 73.1% completely adhered to antiparasitic therapy. Hematologic adverse events (macrocytic anemia and/or neutropenia and/or thrombocytopenia) were diagnosed in 44% of them. The most common adverse event was neutropenia (31%). In most cases, it was not severe and reversed after increase in folinic acid dosage (25.7%) or temporary treatment suspension (1.8%). No infections were observed in association with neutropenic events. Significant associations were detected between macrocytic anemia and lower weight Z score at first medical appointment (P = 0.03), and between severe neutropenia (<500/mm3) and lower weight Z score toward the end of treatment (P = 0.04).

Conclusions:
The high frequency of hematologic adverse events found, especially in malnourished children, highlight the importance of careful monitoring of these children throughout treatment, as well as considering nutritional aspects and the need for higher doses of folinic acid. With adequate monitoring, antiparasitic treatment was feasible and relatively safe in the setting of this large screening program for congenital toxoplasmosis.
Impact of Percutaneous Drainage on Outcome of Intra-abdominal Infection Associated With Pediatric Perforated Appendicitis
Authors: Bonadio William , Langer Miriam , Cueva Julie , Haaland Astrid 
Published: February 2017

Background:
Perforated appendicitis can result in potentially serious complications requiring prolonged medical care. The optimal approach to successfully managing this condition is controversial.

Methods:
Review of 80 consecutive cases of pediatric acute perforated appendicitis with intra-abdominal infection (IAI) medically managed with parenteral antibiotics and percutaneous drainage (PD) during a 7-year period.

Results:
All patients received broad spectrum parenteral antibiotic therapy. One-third were hospitalized for >2 weeks. IAI was identified on admission in 60% compared with developing during hospitalization in 40% of cases. Before performing PD, the mean duration of antibiotic therapy in those who developed IAI during hospitalization was 6 days. IAI cultures yielded 127 bacterial isolates; polymicrobial infection occurred in 65% of cases. Only 7% of aspirates were sterile. The most common pathogens were Escherichia coli (82%), of which 5 isolates exhibited extended-spectrum β-lactamase production, and streptococci (40%). At the time of PD, 60% were febrile (mean duration of in-hospital fever, 7.5 days); 67% defervesced within 24 hours after the procedure. Posthospitalization abdominal complications (recurrent IAI or appendicitis) occurred in one-third of patients.

Conclusions:
Children with perforated appendicitis and IAI often have a complicated and prolonged clinical course. Medical management consisting solely of parenteral antibiotic therapy is frequently ineffective in resolving IAI. Rapid clinical improvement commonly follows PD.
Upper Eyelid Reconstruction Using a Blepharoplasty Flap
Authors: McVeigh Katherine Anne , Caesar Richard 
Published: February 2017

Purpose:The blepharoplasty flap is a relatively simple but under-recognized surgical technique for repairing defects that result from excision of broad-based lesions on the upper eyelid that lie between the eyelid crease and the eyelashes. As this has not been previously published in the literature, the authors aim to increase the awareness of this technique.Methods:The eyelid crease is marked. A line is drawn perpendicular to the crease line along the aspect of the lesion closest to the centre of the eyelid, dividing the eyelid into 4 quarters. The lesion is excised along with the area lying diagonally. An advancement flap is then fashioned from excess skin of the upper eyelid and moved inferiorly to close the defect.Results:The resulting cosmetic results seen postoperatively have been excellent.Conclusions:The blepharoplasty flap is a style of surgical advancement flap that utilizes the tissue that would normally be excised during blepharoplasty. This straightforward technique can prove useful in the surgical repertoire due to its potential to be widely adopted in surgical practice.
Recommendations for a first Core Outcome Measurement set for complex regional PAin syndrome Clinical sTudies (COMPACT)
Authors: Grieve Sharon , Perez Roberto S.G.M. , Birklein Frank , Brunner Florian , Bruehl Stephen , Harden R. Norman , Packham Tara , Gobeil Francois , Haigh Richard , Holly Janet , Terkelsen Astrid , Davies Lindsay , Lewis Jennifer , Thomassen Ilona , Connett Robyn , Worth Tina , Vatine Jean-Jacques , McCabe Candida S. 
Published: February 2017

Abstract
Complex regional pain syndrome (CRPS) is a persistent pain condition that remains incompletely understood and challenging to treat. Historically, a wide range of different outcome measures have been used to capture the multidimensional nature of CRPS. This has been a significant limiting factor in the advancement of our understanding of the mechanisms and management of CRPS. In 2013, an international consortium of patients, clinicians, researchers, and industry representatives was established, to develop and agree on a minimum core set of standardised outcome measures for use in future CRPS clinical research, including but not limited to clinical trials within adult populations. The development of a core measurement set was informed through workshops and supplementary work, using an iterative consensus process. “What is the clinical presentation and course of CRPS, and what factors influence it?” was agreed as the most pertinent research question that our standardised set of patient-reported outcome measures should be selected to answer. The domains encompassing the key concepts necessary to answer the research question were agreed as follows: pain, disease severity, participation and physical function, emotional and psychological function, self-efficacy, catastrophizing, and patient's global impression of change. The final core measurement set included the optimum generic or condition-specific patient-reported questionnaire outcome measures, which captured the essence of each domain, and 1 clinician-reported outcome measure to capture the degree of severity of CRPS. The next step is to test the feasibility and acceptability of collecting outcome measure data using the core measurement set in the CRPS population internationally.
Effect of Methylphenidate on Emotional Dysregulation in Children With Attention-Deficit/Hyperactivity Disorder + Oppositional Defiant Disorder/Conduct Disorder
Authors: Kutlu Ayse , Akyol Ardic Ulku , Ercan Eyup Sabri 
Published: February 2017

Abstract

Background and Aim
Emotional dysregulation (ED) is a frequent feature of attention-deficit/hyperactivity disorder (ADHD). It can be observed as a dysregulation profile or a deficient emotional self-regulation (DESR) profile. Oppositional defiant disorder/conduct disorder (ODD/CD) comorbidity is prevalent in ADHD and known to be related with ED. The first-line treatment of ADHD includes psychostimulants, but their effects on ED are not well studied. This study aimed to evaluate the outcomes of methylphenidate (MPH) treatment on ED in ADHD + ODD/CD cases.

Methods
A total of 118 ADHD + ODD/CD patients with a mean age of 9.0 ± 1.9 years were treated with MPH for 1 year. Also, parents of cases were recruited for a parent-training program, which initiated after first month of MPH treatment. Symptom severity was assessed at baseline and 12th month by Turgay Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–Based Child and Adolescent Behavior Disorders Screening and Rating Scale–Parent Form, Children Depression Inventory, Child Behavior Checklist 4–18 years, and Parental Acceptance and Rejection Questionnaire–Mother Form.

Results
Emotional dysregulation (DESR + DP) was present in 85.6% of cases. Conduct disorder was significantly higher in patients with DP, whereas ODD was significantly higher in the DESR and non-ED groups (P < 0.0001). Symptoms of ADHD and ED were significantly improved with 1-year of MPH treatment (P < 0.05). The improvement in ED was independent of improvement in ADHD symptoms and parent training (P < 0.05).

Conclusions
Emotional dysregulation is highly prevalent in disruptive behavioral disorders as ODD and CD, which are comorbid with ADHD. The MPH treatment is effective on ED independently from other clinical determinants.