Pediatric Nasoorbitoethmoid Fractures: Cause, Classification, and Management.

BACKGROUND: Currently, there is a paucity of information on the presentation and proper management of pediatric nasoorbitoethmoid fractures. The purpose of this study was to examine the incidence, cause, associated injuries, and management of these fractures. Furthermore, the authors sought to assess outcomes after transnasal wiring or suture canthopexy for type III nasoorbitoethmoid fractures. METHODS: A retrospective cohort review was performed of all patients with nasoorbitoethmoid fractures who presented to a Level I trauma center from 1990 to 2010. Charts and computed tomographic imaging were reviewed, and nasoorbitoethmoid fractures were labeled based on the Markowitz-Manson classification system. Patient fracture patterns, demographics, characteristics, and outcomes were recorded. Univariate and multivariate methods were used to compare groups. RESULTS: A total of 63 pediatric patients were identified in the study period. The sample's mean age was 8.78 ± 4.08 years, and 28.6 percent were girls. The sample included 18 type I injuries, 28 type II injuries, and 17 type III injuries. No significant demographic differences were found between patients with type I, II, and III fractures (p > 0.05). Operative intervention was pursued in 16.7, 46.4, and 82.4 percent of type I, II, and III nasoorbitoethmoid fractures, respectively. In patients with type III nasoorbitoethmoid fractures, no patients with transnasal wiring developed telecanthus. CONCLUSIONS: Pediatric nasoorbitoethmoid fractures are uncommon injuries. Type I fracture can often be treated with close observation. However, type II and III injury patterns should be evaluated for operative intervention. Transnasal wiring is an effective method to prevent traumatic telecanthus deformity in type III fracture patterns.

Plastic Surgeons' Perceptions of Financial Conflicts of Interest and the Sunshine Act.

BACKGROUND: It is unknown whether recent legislation known as the Physician Payments Sunshine Act has affected plastic surgeons' views of conflicts of interest (COI). The purpose of this study was to evaluate plastic surgeons' beliefs about COI and their comprehension of the government-mandated Sunshine Act. METHODS: Plastic surgeon members of the American Society of Plastic Surgeons were invited to complete an electronic survey. The survey contained 27 questions that assessed respondents' past and future receipt of financial gifts from industry, awareness of the Sunshine Act, and beliefs surrounding the influence of COI on surgical practice. RESULTS: A total of 322 individuals completed the survey. A majority had previously accepted gifts from industry (n = 236; 75%) and would accept future gifts (n = 181; 58%). Most respondents believed that COI would affect their colleagues' medical practice (n = 190; 61%) but not their own (n = 165; 51%). A majority was aware of the Sunshine Act (n = 272; 89%) and supported data collection on surgeon COI (n = 224; 73%). A larger proportion of young surgeons believed patients would benefit from knowing their surgeon's COI (P = 0.0366). Surgeons who did not expect COI in the future believed financial COI could affect their own clinical practice (P = 0.0221). CONCLUSIONS: Most plastic surgeons have a history of accepting industry gifts but refute their influence on personal clinical practice. Surgeon age and anticipation of future COI affected beliefs about the benefits of COI disclosure to patients and the influence of COI on surgical practice.

The Accuracy of Conflict-of-Interest Disclosures Reported by Plastic Surgeons and Industry.

BACKGROUND: The purpose of this study was to analyze the frequency and nature of self-reported conflict-of-interest disclosures in the plastic surgery literature and to compare these findings to the Physician Payments Sunshine Act database. METHODS: All articles published from August of 2013 through December of 2013 in four major plastic surgery journals were analyzed. For every publication, the conflict-of-interest disclosure statement for each investigator was reviewed. These statements were then compared to transactions of value for each investigator as reported by biomedical companies in the Sunshine Act database. An analysis was performed to identify and characterize specific factors associated with conflict-of-interest disclosures. RESULTS: A total of 1002 independent investigators/authors were identified. Of these, 90 investigators (9 percent) self-reported a conflict of interest. In contrast, a total of 428 authors (42.7 percent) were found to have received transactions of value from a biomedical company according to the Sunshine Act database. Conversely, a total of 22 authors (2.2 percent) self-reported a conflict of interest but were not found to have received transactions of value in the Sunshine Act database. Our analysis found that (1) academic investigators, (2) transactions of value in excess of $500, and (3) publishing articles related to the sponsoring biomedical company were all statistically associated with reporting conflicts of interest (p < 0.0001). CONCLUSIONS: Discordance exists between investigator/authors self-reporting in scientific journals and the government-mandated reporting of conflicts of interest by industry. Factors associated with conflict-of-interest disclosure include academic status, transaction amount, and article content related to the sponsoring biomedical company.

Is Article Methodological Quality Associated With Conflicts of Interest?: An Analysis of the Plastic Surgery Literature.

PURPOSE: Conflicts of interest (COI) are an emerging area of discussion within the field of plastic surgery. Recently, several reports have found that research studies that disclose COI are associated with publication of positive outcomes. We hypothesize that this association is driven by higher-quality studies receiving industry funding. This study aimed to investigate the association between industry support and study methodological quality. METHODS: We reviewed all entries in Plastic and Reconstructive Surgery, Annals of Plastic Surgery, and Journal of Plastic, Reconstructive, and Aesthetic Surgery within a 1-year period encompassing 2013. All clinical research articles were analyzed. Studies were evaluated blindly for methodology quality based on a validated scoring system. An ordinal logistic regression model was used to examine the association between methodology score and COI. RESULTS: A total of 1474 articles were reviewed, of which 483 met our inclusion criteria. These articles underwent methodological quality scoring. Conflicts of interest were reported in 28 (5.8%) of these articles. After adjusting for article characteristics in the ordinal logistic regression analysis, there was no significant association between articles with COI and higher methodological scores (P = 0.7636). CONCLUSIONS: Plastic surgery studies that disclose COI are not associated with higher methodological quality when compared with studies that do not disclose COI. These findings suggest that although the presence of COI is associated with positive findings, the association is not shown to be driven by higher-quality studies.

Citation Rate Predictors in the Plastic Surgery Literature.

BACKGROUND: The purpose of this study is to determine and characterize the scientific and nonscientific factors that influence the rate of article citation in the field of plastic surgery. DESIGN: Cross-sectional study. SETTING: We reviewed all entries in Annals of Plastic Surgery and Journal of Plastic, Reconstructive, and Aesthetic Surgery from January 1, 2007 to December 31, 2007; and Plastic and Reconstructive Surgery from January 1, 2007 to December 31, 2008. All scientific articles were analyzed and several article characteristics were extracted. The number of citations at 5 years was collected as the outcome variable. A multivariable analysis was performed to determine which variables were associated with higher citations rates. RESULTS: A total of 2456 articles were identified of which only 908 fulfilled the inclusion criteria. Most studies were publications in the fields of reconstructive (26.3%) or pediatric/craniofacial (17.6%) surgery. The median number of citations 5 years from publication was 8. In the multivariable analysis, factors associated with higher citations rates were subspecialty field (p = 0.0003), disclosed conflict of interest (p = 0.04), number of authors (p = 0.04), and journal (p = 0.02). CONCLUSION: We have found that higher level of evidence (or other study methodology factors) is not associated with higher citation rates. Instead, conflict of interest, subspecialty topic, journal, and number of authors are strong predictors of high citation rates in plastic surgery.

Ear biometrics for patient identification in global health: a cross-sectional study to test the feasibility of a simplified algorithm.

BACKGROUND: One of the greatest public health challenges in low- and middle-income countries (LMICs) is identifying people over time and space. Recent years have seen an explosion of interest in developing electronic approaches to addressing this problem, with mobile technology at the forefront of these efforts. We investigate the possibility of biometrics as a simple, cost-efficient, and portable solution. Common biometrics approaches include fingerprinting, iris scanning and facial recognition, but all are less than ideal due to complexity, infringement on privacy, cost, or portability. Ear biometrics, however, proved to be a unique and viable solution. METHODS: We developed an identification algorithm then conducted a cross sectional study in which we photographed left and right ears from 25 consenting adults. We then conducted re-identification and statistical analyses to identify the accuracy and replicability of our approach. RESULTS: Through principal component analysis, we found the curve of the ear helix to be the most reliable anatomical structure and the basis for re-identification. Although an individual ear allowed for high re-identification rate (88.3%), when both left and right ears were paired together, our rate of re-identification amidst the pool of potential matches was 100%. CONCLUSIONS: The results of this study have implications on future efforts towards building a biometrics solution for patient identification in LMICs. We provide a conceptual platform for further investigation into the development of an ear biometrics identification mobile application.

The Impact of Financial Conflicts of Interest in Plastic Surgery: Are They All Created Equal?

BACKGROUND: Recently, several studies have demonstrated that articles that disclose conflicts of interests (COI) are associated with publication of positive results. The purpose of this study was to learn more about the different types of COI as they relate to the general topic of COI in plastic surgery. Specifically, we aimed to examine whether different types of COI are more likely than others to be associated with the presentation of positive findings. METHODS: We reviewed all original articles in Annals of Plastic Surgery, Journal of Plastic, Reconstructive, and Aesthetic Surgery, and Plastic & Reconstructive Surgery from January 1, 2012, to December 31, 2013. All scientific articles were analyzed, and several article characteristics were extracted. Disclosed COI were categorized into the following categories: consultant/employee, royalties/stock options, and research support. The findings reported in each article abstract were blindly graded as reporting a positive, negative, neutral, or not applicable result. A multivariable analysis was performed to determine whether an association existed between certain types of COI and publication of positive conclusions. RESULTS: A total of 3124 articles were identified of which 1185 fulfilled the inclusion criteria. Financial COI were reported in 153 studies (12.9%). The most common type of COI was "research support" (7.3%), whereas the least common was "royalties/stock options" (1.2%). Rates of different types of COI varied significantly by plastic surgery subspecialty field (P < 0.001). In the multivariable analysis, authors who disclosed COI related to research support, consultant/employee, and royalties/stock options were 1.31, 6.62, and 8.72 times more likely, respectively, to publish positive findings when compared with authors that disclosed no COI after correcting for potential confounding factors. However, consultancy/employee status was the only COI category statistically associated with publication of positive results (P < 0.001). CONCLUSIONS: Self-reported COI are uncommon in plastic surgery research. Our results provide evidence that certain types of financial COI are more likely than others to be associated with the presentation of positive findings. This analysis suggests that certain investigators may be more biased, consciously or unconsciously, by the type of financial benefit offered by industry.

Financial Conflicts of Interest: An Association between Funding and Findings in Plastic Surgery.

BACKGROUND: Despite a growing interest in examining the effects of industry funding on research in plastic surgery, no study to date has comprehensively examined the effects of financial conflicts of interest on publication outcomes. The authors investigated the association between financial conflicts of interest and reported study findings in plastic surgery research. METHODS: The authors reviewed all entries in Plastic and Reconstructive Surgery, Annals of Plastic Surgery, and Journal of Plastic, Reconstructive & Aesthetic Surgery from January 1, 2012, to December 31, 2012. All clinical and basic science articles were analyzed. The following article characteristics were extracted: self-reported financial conflicts of interest, sample size, level of evidence, study design, and prospectiveness. The findings reported in each abstract were blindly graded as not applicable, negative, or positive. RESULTS: Of the 1650 abstracts that resulted from the authors' initial search, 568 fulfilled the inclusion criteria. The majority of the included articles covered breast (20.8 percent), experimental (19.7 percent), and general reconstruction (31.69 percent). Financial conflicts of interest were disclosed in only 17.6 percent of the articles. Of the total studies that met inclusion criteria, 66.2 percent were reviewed as having positive outcomes, and 33.8 percent were reviewed as having negative or not applicable results. Studies that disclosed a financial conflict of interest were 7.12 times more likely (p < 0.0001) to present a positive outcome over a negative outcome compared with studies with no financial conflict of interest. CONCLUSION: Investigators with a financial conflict of interest are significantly more likely to publish plastic surgery studies with a positive conclusion compared with investigators with no conflicts of interest.

Rare genetic variant analysis on blood pressure in related samples.

The genetic variants associated with blood pressure identified so far explain only a small proportion of the total heritability of this trait. With recent advances in sequencing technology and statistical methodology, it becomes feasible to study the association between blood pressure and rare genetic variants. Using real baseline phenotype data and imputed dosage data from Genetic Analysis Workshop 18, we performed a candidate gene association analysis. We focused on 8 genes shown to be associated with either systolic or diastolic blood pressure to identify the association with both common and rare genetic variants, and then did a genome-wide rare-variant analysis on blood pressure. We performed association analysis for rare coding and splicing variants within each gene region and all rare variants in each sliding window, using either burden tests or sequence kernel association tests accounting for familial correlation. With a sample size of only 747, we failed to find any novel associated genetic loci. Consequently, we performed analyses on simulated data, with knowledge of the underlying simulating model, to evaluate the type I error rate and power for the methods used in real data analysis.

The impact of conflicts of interest in plastic surgery: an analysis of acellular dermal matrix, implant-based breast reconstruction.

BACKGROUND: Although conflicts of interest in biomedical research have received significant attention, the impact of conflicts of interest on surgical outcomes has not been fully explored. METHODS: A systematic electronic search of the literature was performed for studies that evaluated surgical outcomes in acellular dermal matrix and non-acellular dermal matrix implant-based breast reconstruction. Surgical complications, including infection, seroma, hematoma, necrosis, and explantation, were used as outcome metrics and extracted from studies. Surgical outcomes were then pooled and compared between studies that disclosed conflicts of interest and those that did not disclose conflicts of interest. RESULTS: A total of 776 abstracts were identified, of which only 35 fulfilled the authors' inclusion criteria. Conflicts of interest were reported in 14 of these abstracts (40 percent). The pooled data from studies that reported no conflicts of interest and studies that reported conflicts of interest included a total of 8241 and 5384 breasts and 2852 and 1864 patients, respectively. Considered collectively, surgical complications were less common in studies that reported a conflict of interest than in studies that reported no conflicts of interest. When surgical outcome data were further stratified by acellular dermal matrix use, surgical complications were less common in studies with conflicts of interest when acellular dermal matrix was used. However, when acellular dermal matrix was not used, surgical complications were similar between authors that reported a conflict of interest and those that did not report a conflict of interest. CONCLUSIONS: Self-reported conflicts of interest are common in implant-based breast reconstruction research. Studies authored by groups with conflicts of interest are significantly associated with reporting lower surgical complications and therefore describing positive research findings, especially when industry-marketed products are being used in the study. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Prediction of fetal hemoglobin in sickle cell anemia using an ensemble of genetic risk prediction models.

BACKGROUND: Fetal hemoglobin (HbF) is the major modifier of the clinical course of sickle cell anemia. Its levels are highly heritable, and its interpersonal variability is modulated in part by 3 quantitative trait loci that affect HbF gene expression. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) in these quantitative trait loci that are highly associated with HbF but explain only 10% to 12% of the variance of HbF. Combining SNPs into a genetic risk score can help to explain a larger amount of the variability of HbF level, but the challenge of this approach is to select the optimal number of SNPs to be included in the genetic risk score. METHODS AND RESULTS: We developed a collection of 14 models with genetic risk score composed of different numbers of SNPs and used the ensemble of these models to predict HbF in patients with sickle cell anemia. The models were trained in 841 patients with sickle cell anemia and were tested in 3 independent cohorts. The ensemble of 14 models explained 23.4% of the variability in HbF in the discovery cohort, whereas the correlation between predicted and observed HbF in the 3 independent cohorts ranged between 0.28 and 0.44. The models included SNPs in BCL11A, the HBS1L-MYB intergenic region, and the site of the HBB gene cluster, quantitative trait loci previously associated with HbF. CONCLUSIONS: An ensemble of 14 genetic risk models can predict HbF levels with accuracy between 0.28 and 0.44, and the approach may also prove useful in other applications.

A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia.

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21-5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry.

Evaluation of an ensemble of genetic models for prediction of a quantitative trait.

Many genetic markers have been shown to be associated with common quantitative traits in genome-wide association studies. Typically these associated genetic markers have small to modest effect sizes and individually they explain only a small amount of the variability of the phenotype. In order to build a genetic prediction model without fitting a multiple linear regression model with possibly hundreds of genetic markers as predictors, researchers often summarize the joint effect of risk alleles into a genetic score that is used as a covariate in the genetic prediction model. However, the prediction accuracy can be highly variable and selecting the optimal number of markers to be included in the genetic score is challenging. In this manuscript we present a strategy to build an ensemble of genetic prediction models from data and we show that the ensemble-based method makes the challenge of choosing the number of genetic markers more amenable. Using simulated data with varying heritability and number of genetic markers, we compare the predictive accuracy and inclusion of true positive and false positive markers of a single genetic prediction model and our proposed ensemble method. The results show that the ensemble of genetic models tends to include a larger number of genetic variants than a single genetic model and it is more likely to include all of the true genetic markers. This increased sensitivity is obtained at the price of a lower specificity that appears to minimally affect the predictive accuracy of the ensemble.

Genome-wide meta-analysis of systolic blood pressure in children with sickle cell disease.

In pediatric sickle cell disease (SCD) patients, it has been reported that higher systolic blood pressure (SBP) is associated with increased risk of a silent cerebral infarction (SCI). SCI is a major cause of neurologic morbidity in children with SCD, and blood pressure is a potential modulator of clinical manifestations of SCD; however, the risk factors underlying these complications are not well characterized. The aim of this study was to identify genetic variants that influence SBP in an African American population in the setting of SCD, and explore the use of SBP as an endo-phenotype for SCI. We conducted a genome-wide meta-analysis for SBP using two SCD cohorts, as well as a candidate screen based on published SBP loci. A total of 1,617 patients were analyzed, and while no SNP reached genome-wide significance (P-value<5.0 x 10(-8)), a number of suggestive candidate loci were identified. The most significant SNP, rs7952106 (P-value=8.57 x 10(-7)), was in the DRD2 locus on chromosome 11. In a gene-based association analysis, MIR4301 (micro-RNA4301), which resides in an intron of DRD2, was the most significant gene (P-value=5.2 x 10(-5)). Examining 27 of the previously reported SBP associated SNPs, 4 SNPs were nominally significant. A genetic risk score was constructed to assess the aggregated genetic effect of the published SBP variants, demonstrating a significant association (P=0.05). In addition, we also assessed whether these variants are associated with SCI, validating the use of SBP as an endo-phenotype for SCI. Three SNPs were nominally associated, and only rs2357790 (5' CACNB2) was significant for both SBP and SCI. None of these SNPs retained significance after Bonferroni correction. Taken together, our results suggest the importance of DRD2 genetic variation in the modulation of SBP, and extend the aggregated importance of previously reported SNPs in the modulation of SBP in an African American cohort, more specifically in children with SCD.