Incidence of ophthalmologic pathology and associated risk factors in orbital fractures at a level I trauma centre.

OBJECTIVE: To estimate the incidence of ophthalmologic pathology at presentation of patients with orbital fracture to a level I trauma centre and the most significant associated risk factors. METHODS: A total of 244 patients with 278 fractured orbits over a 2-year period at a level I trauma centre were reviewed. The primary outcome was the incidence of urgent ophthalmologic pathology, defined as requiring attention without delay. Patient demographics, history, findings on radiographic imaging, and physical examination findings at initial and follow-up examinations were recorded. Odds ratios with 95% confidence intervals were calculated. RESULTS: On initial examination and follow-up, 9.7% of orbits had ophthalmologic pathology. Only 3 patients (1.1%) had urgent pathology, including orbital compartment syndrome and globe rupture, whereas 22 patients (7.9%) had semiurgent pathology and 4 patients (1.4%) had nonurgent pathology. Subjective decreased vision (odds ratio [OR] = 3.5; p = 0.021), assault-related injuries (OR = 2.4; p = 0.036), work-related injuries (OR = 7.7; p = 0.004), afferent pupillary defect (OR = 19.2; p = 0.017), anisocoria (OR = 7.8; p = 0.001), and symmetrical extraocular movement limitation (OR = 5.2; p = 0.003) and fixed pupil (OR = 16.9; p < 0.001) had statistically significant odds ratios associated with pathology. Patient sex, eye involved, intoxication, anticoagulation, and antiplatelets, as well as previous ocular surgery, were not associated with pathology. CONCLUSIONS: Most orbital fractures do not present with ophthalmologic pathology. Subjective vision loss, history of assault or work trauma, and pupil abnormalities on examination were the greatest risk factors for pathology. Our results highlight the most important factors on patient presentation that should prompt first responders to seek urgent ophthalmologic consultation.

Significance of subconjunctival hemorrhage in predicting ocular pathology for patients with orbital fracture.

OBJECTIVE: Subconjunctival hemorrhage (SCH) is a common presentation in patients with orbital trauma and often warrants investigation of underlying ocular pathology. Our study aims to assess the significance of SCH severity, graded in a spatial 0-360° manner, as a predictor for ocular pathology in patients with orbital fracture. DESIGN: Retrospective chart review. PARTICIPANTS: Patients with fractured orbits (n = 265) presenting to a level 1 trauma centre between August 2015 and January 2018. METHODS: Key elements of ophthalmic assessment, including visual acuity, SCH (0-360°), anterior- and posterior-segment examination, Hertel exophthalmometry, and ocular pathology, were recorded. Simple logistic regression assessed for association between SCH severity and ocular pathology. Odds ratios (ORs) were calculated with 95% CI. RESULTS: Among the 265 fractured orbits, 158 (59.6%) presented with no SCH, and 107 (40.4%) had some degree of SCH. Ocular pathology was noted in 24 fractured orbits (9%). Most common pathologies included entrapment (22.2%), hyphema (16.7%), traumatic optic neuropathy (8.3%), and commotio retinae (8.3%). Simple logistic regression revealed a higher incidence of ocular pathology with increasing severity of SCH from 0-360° (OR = 1.004; 95% CI 1.001-1.007; p = 0.0085). In addition, χ2 analysis demonstrated a higher proportion of ocular pathology in 181-270° (25.0%; p = 0.0466) and 271-360° SCH subgroups (26.3%; p = 0.0031) compared with the 0° SCH subgroup (6.3%). CONCLUSIONS: Our findings suggest that there is some correlation between the extent of SCH and ocular pathology. However, patient care and investigations should continue to be directed by a full clinical assessment of patients with orbital trauma.

Clinical correlations of extraocular motility limitation pattern in orbital fracture cases: a retrospective cohort study in a level 1 trauma centre.

PURPOSE: Ocular pathology (OP) following orbital fracture can vary vastly in complexity and severity. Extra-ocular motility (EOM) limitations are frequently present in orbital trauma cases, with patterns of duction limitations being symmetrical or asymmetrical. The aim of this study was to identify if there was any association between increased OP following orbital fracture cases based on the pattern of EOM deficits. METHODS: This is a retrospective cohort study of patients with fractured orbits presenting with or without EOM limitations to a level 1 trauma center between August 2015 to January 2018. All pertinent elements of the ophthalmic examination were recorded. Outcome measures: Chi-square analyses assessed for association between symmetrical or asymmetrical EOM limitation and OP. Odds ratios were calculated with 95% confidence interval. RESULTS: 278 orbits with wall fractures were included in this study. A significant correlation between EOM limitation and increased OP following orbital trauma was found (p = 0.000081). Cases with symmetrical and asymmetrical EOM limitation were 7.9 (95%CI: 2.3-27.2) and 5.22 (95%CI: 1.9-13.9) times more likely to have OP than cases with no EOM limitation, respectively. With extraocular muscle entrapment excluded, cases with symmetrical limitations had a significantly higher incidence of OP than cases with asymmetrical limitations (p = 0.0161). CONCLUSIONS: OP is frequently observed in cases of orbital fracture. While any EOM limitations should prompt the clinicians to anticipate OP, intra-ocular injury may be more likely in cases of symmetrical EOM limitation. Future prospective studies are needed to further elucidate the relationship between EOM symmetricity and OP following orbital trauma.

Primary care assessment of orbital trauma at a level 1 trauma centre.

OBJECTIVE: With increasing constraints on our publicly funded health care system, appropriate triage of trauma patients is becoming pivotal, making the primary care assessment (PCA) invaluable. Our study aims to compare the initial assessment of patients with orbital fractures with that conducted by the ophthalmology service. DESIGN: Retrospective chart review. PARTICIPANTS: 243 patients with 277 fractured orbits presenting to a level 1 trauma centre seen between August 2015 and January 2018. METHODS: Key elements of the PCA, including subjective vision loss, visual acuity, intraocular pressure, pupil examination, and extraocular movements, were documented and compared with the assessment by the ophthalmology service as the control. The primary outcome was inter-rater reliability as estimated by Cohen's kappa (κ) coefficient. Secondary outcomes included the sensitivity and specificity, as well as the rate of completion of examination components. RESULTS: PCA examination findings agreed with the ophthalmology service on most components of the examination with the highest agreement with relative afferent pupillary defects and detection of hyphemas (κ = 1). Primary care physicians less often performed most aspects of the assessment. Among performed components of the examination, the average sensitivity was 60.6%, and the average specificity was 84.2%. CONCLUSIONS: Our results show good inter-rater reliability of the PCA compared with the ophthalmology examination but low rate of completion of examination components, suggesting a potential overdependence on the ophthalmology assessment. Given the limited resources of the public health care system, our study may highlight the PCA as a potential focus to improve effective and safe patient management.

Incidence and outcomes of retrobulbar hematoma diagnosed by computed tomography in cases of orbital fracture.

OBJECTIVE: Retrobulbar hemorrhage (RBH) is a potentially sight-threatening complication of orbital fractures causing an orbital compartment syndrome (OCS). RBH causing OCS is regarded as a clinical diagnosis when evidence of optic nerve compression is found. Nonetheless, many patients with facial trauma will have received imaging by computed tomography (CT) on which there is documented RBH, with or without signs of OCS. The aim of this study was to identify the incidence and describe the outcomes of these CT-diagnosed RBH. METHODS: This is a retrospective chart review of patients with orbital fractures for which ophthalmology was consulted. Confirmation of orbital fracture and presence of an RBH on facial-bones CT was recorded. Patient demographics, proptosis, visual acuity, intraocular pressure and interventions received at initial visit and follow-up were recorded. RESULTS: 292 orbits with wall fractures were identified. 94 (32.2%) were documented by CT to have RBH. Of these orbits, only one (1.1%) was diagnosed with OCS receiving canthotomy and cantholysis. 53 orbits with initial CT-diagnosed retrobulbar hematoma were seen in follow-up a week or more later, none of which had developed signs of OCS or needed medical or surgical intervention for OCS. CONCLUSIONS: RBH is a frequently reported finding on CT in cases of orbital fractures. In this study, almost all of these CT-diagnosed RBH did not develop OCS initially or by the time of follow-up. CT presence of RBH is not an accurate predictor for OCS, and the diagnosis and treatment of OCS should be directed clinically.

Posterior vitreous detachment and incidence of delayed retinal breaks: a retrospective, 2-year study at an academic centre.

OBJECTIVE: Posterior vitreous detachment (PVD) is common in older patients, particularly postcataract surgery. Patients are typically followed 4 to 6 weeks after the initial presentation. The study goal was to assess the rate of new retinal tears for patients without new symptoms on routine follow-up. METHODS: This is a multisite, retrospective cohort study of all patients presenting to the emergency departments at an academic health centre in a 2-year period diagnosed with uncomplicated PVD. Patient demographics, pastocular surgery, retinal findings at the first and second examinations, and the identity of the examiner were recorded. The primary outcome was absence of new retinal tears or pathology on follow-up. RESULTS: One hundred sixty-six patients were identified, and 105 patients were present for both an initial and follow-up examination (median, 6 weeks). No patients had any new pathology on the follow-up examination. Most patients (n = 62) were seen initially by one of 15 residents alone, and most patients (n = 80) were seen at follow-up by one of 10 staff from specialties of comprehensive, uveitis, neuro-ophthalmology, cornea, and retina. The remaining 25 patients were seen in follow-up by residents. CONCLUSION: To our knowledge, this is the first study on the incidence of delayed retinal breaks with the examination performed by a variety of residents and comprehensive and subspecialist staff. Our results suggest there may be limited benefit to routine follow-up of PVD patients without new symptoms, including when followed by nonretina ophthalmologists. These findings could allow for better health care resources management.

Co-existing feedback loops generate tissue-specific circadian rhythms.

Gene regulatory feedback loops generate autonomous circadian rhythms in mammalian tissues. The well-studied core clock network contains many negative and positive regulations. Multiple feedback loops have been discussed as primary rhythm generators but the design principles of the core clock and differences between tissues are still under debate. Here we use global optimization techniques to fit mathematical models to circadian gene expression profiles for different mammalian tissues. It turns out that for every investigated tissue multiple model parameter sets reproduce the experimental data. We extract for all model versions the most essential feedback loops and find auto-inhibitions of period and cryptochrome genes, Bmal1-Rev-erb-α loops, and repressilator motifs as possible rhythm generators. Interestingly, the essential feedback loops differ between tissues, pointing to specific design principles within the hierarchy of mammalian tissue clocks. Self-inhibitions of Per and Cry genes are characteristic for models of suprachiasmatic nucleus clocks, whereas in liver models many loops act in synergy and are connected by a repressilator motif. Tissue-specific use of a network of co-existing synergistic feedback loops could account for functional differences between organs.

Genomes of ubiquitous marine and hypersaline Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira spp. encode a diversity of mechanisms to sustain chemolithoautotrophy in heterogeneous environments.

Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1-3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb3 cytochrome c oxidase, some also encode cytochrome bd-type quinol oxidase or ba3 -type cytochrome c oxidase, which could facilitate growth under different oxygen tensions, or maintain redox balance. Carboxysome operons are present in most, with genes downstream encoding transporters from four evolutionarily distinct families, which may act with the carboxysomes to form CO2 concentrating mechanisms. These adaptations to habitat variability likely contribute to the cosmopolitan distribution of these organisms.

Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National Commercially Insured Population: The ABOUT Study.

IMPORTANCE: BRCA genetic testing has substantial public health impact, yet little is known of the real-world experiences of the more than 100 000 Americans undergoing testing annually. OBJECTIVE: To identify factors associated with use of BRCA testing, assess whether delivery of genetic counseling and testing services adheres to professional guidelines, and measure the impact on patient-reported outcomes. DESIGN, SETTING, AND PARTICIPANTS: The American BRCA Outcomes and Utilization of Testing (ABOUT) Study analyzed data from a consecutive national series of 11 159 women whose clinicians ordered BRCA testing between December 2011 and December 2012. Aetna mailed recruitment information across the United States to commercial health plan members whose clinicians had ordered BRCA testing. A total of 3874 women (34.7%) completed questionnaires. Deidentified clinician-reported data from all respondents and a random sample of 2613 nonrespondents were also analyzed. MAIN OUTCOMES AND MEASURES: The proportion of eligible participants who met testing criteria and respondents' report of receiving genetic counseling by a genetics clinician and its association with BRCA knowledge, understanding, and satisfaction were assessed. RESULTS: Among 3628 women respondents whose clinicians ordered comprehensive BRCA testing, most were white non-Hispanic (2502 [69.0%]), college educated (2953 [81.4%]), married (2751 [75.8%]), and had higher incomes (2011 [55.4%]). Approximately 16.4% (596) did not meet testing criteria. Mutations were identified in 161 (5.3%) of these women who received comprehensive testing. Only 1334 (36.8%) reported receiving genetic counseling from a genetics clinician prior to testing; the lowest rates (130 [12.3%]) were among patients of obstetrician/gynecologists. The most commonly reported reason for not receiving this clinical service was lack of clinician recommendation. Those who received it demonstrated greater knowledge about BRCA (mean score difference adjusted for demographics and clinician specialty, ß = 0.99 [95% CI, 0.83-1.14]; P < .001) and expressed greater understanding (ß = 0.47 [95% CI, 0.41-0.54]; P < .001) and satisfaction (ß = 2.21 [95% CI, 1.60-2.81]; P < .001). CONCLUSIONS AND RELEVANCE: Despite improved patient knowledge, understanding, and satisfaction among patients who receive genetic counseling provided by a genetics clinician, as well as multiple guidelines emphasizing the importance of genetic counseling, most US women undergoing BRCA genetic testing do not receive this clinical service. Lack of physician recommendation is the most commonly reported reason. These findings demonstrate important gaps in clinical genetics services. Recently mandated coverage of genetic counseling services as a preventive service without patient cost sharing should contribute to improving clinical genetics services and associated outcomes in the future.

American BRCA Outcomes and Utilization of Testing (ABOUT) study: a pragmatic research model that incorporates personalized medicine/patient-centered outcomes in a real world setting.

Research to date regarding identification and management of hereditary breast and ovarian cancer syndrome (HBOC) in the U.S. has been confined primarily to academic center-based studies with limited patient engagement. To begin to understand and address the current gaps and disparities in delivery of services for the appropriate identification and optimal risk management of individuals with HBOC, we designed and have initiated the American BRCA Outcomes and Utilization of Testing (ABOUT) Study. ABOUT relies on a collaborative patient advocacy, academic and industry partnership to recruit and engage U.S. individuals who are at increased risk for HBOC and investigate their experiences, decisions and outcomes. It utilizes an extensive research infrastructure, including an interactive web-based data system and electronic interfaces for secure online participation and automated data exchange. We describe the novel recruitment approach that was designed for collaboration with a national commercial health plan partner to identify all individuals for whom a healthcare provider orders a BRCA test and mail to each individual an invitation to participate and study packet. The study packet contains detailed information about the study, a baseline questionnaire and informed consent for participation in the study, for release of relevant medical and health plan records and for ongoing research engagement. This approach employs patient-reported, laboratory-reported and health plan-reported outcomes and facilitates longitudinal engagement. We believe that the type of innovative methodology and collaborative framework we have developed for ABOUT is an ideal foundation for a patient-powered research network. This approach can make substantial contributions to identifying current and best practices in HBOC, leading to improved strategies for clinical care and optimal health outcomes among individuals with high inherited risk for cancer.