Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes.

PURPOSE: Where multiple in silico tools are concordant, the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework affords supporting evidence toward pathogenicity or benignity, equivalent to a likelihood ratio of ~2. However, limited availability of "clinical truth sets" and prior use in tool training limits their utility for evaluation of tool performance. METHODS: We created a truth set of 9,436 missense variants classified as deleterious or tolerated in clinically validated high-throughput functional assays for BRCA1, BRCA2, MSH2, PTEN, and TP53 to evaluate predictive performance for 44 recommended/commonly used in silico tools. RESULTS: Over two-thirds of the tool-threshold combinations examined had specificity of <50%, thus substantially overcalling deleteriousness. REVEL scores of 0.8-1.0 had a Positive Likelihood Ratio (PLR) of 6.74 (5.24-8.82) compared to scores <0.7 and scores of 0-0.4 had a Negative Likelihood Ratio (NLR) of 34.3 (31.5-37.3) compared to scores of >0.7. For Meta-SNP, the equivalent PLR = 42.9 (14.4-406) and NLR = 19.4 (15.6-24.9). CONCLUSION: Against these clinically validated "functional truth sets," there was wide variation in the predictive performance of commonly used in silico tools. Overall, REVEL and Meta-SNP had best balanced accuracy and might potentially be used at stronger evidence weighting than current ACMG/AMP prescription, in particular for predictions of benignity.

Item selection for 12-item short forms of the Knee injury and Osteoarthritis Outcome Score (KOOS-12) and Hip disability and Osteoarthritis Outcome Score (HOOS-12).

OBJECTIVE: To develop 12-item short forms (KOOS-12, HOOS-12) of the 42-item Knee injury and Osteoarthritis Outcome Score (KOOS) and 40-item Hip disability and Osteoarthritis Outcome Score (HOOS) that represent the full-length instruments sufficiently to provide joint-specific pain, function and quality of life (QOL) domain and summary joint impact scores. This paper describes KOOS-12 and HOOS-12 item selection. Subsequent papers will examine KOOS-12 and HOOS-12 reliability, validity and responsiveness. DESIGN: Items were selected based on qualitative information from patients, clinicians and KOOS/HOOS translators and analysis of data from 1,395 knee osteoarthritis (OA) and 1,281 hip OA patients from the FORCE-TJR cohort who completed KOOS or HOOS before and after total joint replacement (TJR). Item response theory models and computerized adaptive test (CAT) simulations were used to identify items that best measured patients' levels of pain and function pre- and post-TJR. KOOS-12/HOOS-12 items were selected based on content, coverage of a wide measurement range, high item information, item usage in CAT simulations, scale-level properties (reliability, validity, responsiveness), and qualitative information. RESULTS: KOOS-12 and HOOS-12 each included a pain frequency item and three items measuring pain during increasingly difficult activities (sitting/lying, walking, up/down stairs); function items about standing, rising from sitting, getting in/out of a car, and twisting/pivoting (KOOS-12) or walking on an uneven surface (HOOS-12); and the original 4-item QOL scale. CONCLUSIONS: This study demonstrated the benefits of examining patient-reported outcome measures using modern psychometric methods, to create short forms with diverse content that provide domain-specific and summary joint impact scores.

A 12-item short form of the Hip disability and Osteoarthritis Outcome Score (HOOS-12): tests of reliability, validity and responsiveness.

OBJECTIVE: To evaluate reliability, validity and responsiveness of HOOS-12, a 12-item short form of the 40-item Hip disability and Osteoarthritis Outcome Score (HOOS). HOOS-12 provides Pain, Function and Quality of Life (QOL) scale scores and a summary hip impact score. DESIGN: Data from 1,273 FORCE-TJR hip osteoarthritis (OA) patients who completed HOOS before and six and 12 months after total hip replacement (THR) were analyzed. HOOS-12 includes a pain frequency item and three items measuring pain during increasingly difficult (sitting/lying, walking, stairs) activities; function items about standing, rising from sitting, getting in/out of a car, and walking on an uneven surface; and the 4-item HOOS QOL scale. Percent computable scale scores, floor and ceiling effects, internal consistency reliability, validity (scale correlations, tests of known groups validity using one-way analysis of variance (ANOVA)), and responsiveness (effect sizes (ES), standardized response means (SRM)) were compared for HOOS-12, full-length HOOS, HOOS-PS and HOOS, JR. RESULTS: Internal consistency reliability was above 0.70 for all HOOS-12 scales and above 0.90 for the HOOS-12 Summary score. Validity and responsiveness of HOOS-12 Pain, Function and QOL scales were satisfactory and reached similar conclusions as comparable full-length HOOS scales. The HOOS-12 Summary score was highly responsive in discriminating between groups who differed in global ratings of post-THR change in physical capabilities and had high ES and SRM standardized response means. CONCLUSIONS: HOOS-12 was a reliable and valid alternative to HOOS in THR patients with moderate to severe OA and provided three domain-specific and summary hip impact scores with substantially reduced respondent burden.

A 12-item short form of the Knee injury and Osteoarthritis Outcome Score (KOOS-12): tests of reliability, validity and responsiveness.

OBJECTIVE: To evaluate reliability, validity and responsiveness of KOOS-12, a 12-item short form of the 42-item Knee injury and Osteoarthritis Outcome Score (KOOS) that provides Pain, Function and Quality of Life (QOL) scale scores and a summary knee impact score. DESIGN: Data from 1,392 knee osteoarthritis (OA) patients from the FORCE-TJR research cohort who completed KOOS before and 6 and 12 months after total knee replacement (TKR) were analyzed. KOOS-12 includes a pain frequency item and three items measuring pain during increasingly difficult (sitting/lying, walking, stairs) activities; function items about standing, rising from sitting, getting in/out of a car, and twisting/pivoting; and the 4-item KOOS QOL scale. Percent computable scale scores, floor and ceiling effects, internal consistency reliability, validity (scale correlations, tests of known groups validity using one-way analysis of variance (ANOVA)) and responsiveness (effect sizes, standardized response means) were compared for the KOOS-12, full-length KOOS, KOOS-PS and KOOS, JR. RESULTS: Internal consistency reliability was above 0.70 for all KOOS-12 scales and ≥0.90 for the KOOS-12 Summary score. Validity and responsiveness of KOOS-12 Pain, Function and QOL scales was satisfactory and reached similar conclusions as comparable full-length KOOS scales. The KOOS-12 Summary score was most responsive in discriminating between groups who differed in global ratings of post-TKR change in physical capabilities and had the highest effect sizes and standardized response means. CONCLUSIONS: KOOS-12 was a reliable and valid alternative to KOOS in TKR patients with moderate to severe OA and provided three domain-specific and summary knee impact scores with substantially reduced respondent burden.

Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome.

BACKGROUND: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES). METHODS: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 × 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study. RESULTS: Overall, imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36). CONCLUSIONS: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.

Sleep disorders and inflammatory disease activity: chicken or the egg?

Sleep dysfunction is a highly prevalent condition that has long been implicated in accelerating disease states characterized by having an inflammatory component such as systemic lupus erythematosus, HIV, and multiple sclerosis. Inflammatory bowel disease (IBD) is a chronic, debilitating disease that is characterized by waxing and waning symptoms, which are a direct result of increased circulating inflammatory cytokines. Recent studies have demonstrated sleep dysfunction and the disruption of the circadian rhythm to result in an upregulation of inflammatory cytokines. Not only does this pose a potential trigger for disease flares but also an increased risk of malignancy in this subset of patients. This begs to question whether or not there is a therapeutic role of sleep cycle and circadian rhythm optimization in the prevention of IBD flares. Further research is needed to clarify the role of sleep dysfunction and alterations of the circadian rhythm in modifying disease activity and also in reducing the risk of malignancy in patients suffering from IBD.

Genetic and environmental effects on early growth and performance in purebred Holstein, Jersey, and reciprocal crossbred calves.

For this designed experiment, Holstein × Holstein (n=28), Jersey × Jersey (n=10), Holstein × Jersey (n=15), and Jersey × Holstein (n=15) bull and heifer calves were compared for body weight (BW), dry matter intake, feed efficiency, hip height, BW gain to 42 and 56 d, and days to weaning from birth to 8 wk. All traits were examined for purebred, maternal, and heterotic genetic effects. Purebred genetic effects significantly favored the Holstein breed for BW, dry matter intake, hip height, and BW gain to 42 and 56 d. Heterotic genetic effects were present for dry matter intake and hip height. Calf sex affected BW and BW gain to 56 d. Our results indicate that early calf growth is influenced primarily by purebred effects favoring the Holstein breed and to a lesser extent heterosis.

Geometric-phase interference in a Mn12 single-molecule magnet with fourfold rotational symmetry.

We study the magnetic relaxation rate Γ of the single-molecule magnet Mn(12)-tBuAc as a function of the magnetic field component H(T) transverse to the molecule's easy axis. When the spin is near a magnetic quantum tunneling resonance, we find that Γ increases abruptly at certain values of H(T). These increases are observed just beyond values of H(T) at which a geometric-phase interference effect suppresses tunneling between two excited energy levels. The effect is washed out by rotating H(T) away from the spin's hard axis, thereby suppressing the interference effect. Detailed numerical calculations of Γ using the known spin Hamiltonian accurately reproduce the observed behavior. These results are the first experimental evidence for geometric-phase interference in a single-molecule magnet with true fourfold symmetry.

Evaluation of a role functioning computer adaptive test (RF-CAT).

OBJECTIVES: To evaluate the validity and participants' acceptance of an online assessment of role function using computer adaptive test (RF-CAT). METHODS: The RF-CAT and a set of established quality of life instruments were administered in a cross-sectional study in a panel sample (n = 444) recruited from the general population with over-selection of participants with selected self-report chronic conditions (n = 225). The efficiency, score accuracy, validity, and acceptability of the RF-CAT were evaluated and compared to existing measures. RESULTS: The RF-CAT with a stopping rule of six items with content balancing used 25 of the available bank items and was completed on average in 66 s. RF-CAT and the legacy tools scores were highly correlated (.64-.84) and successfully discriminated across known groups. The RF-CAT produced a more precise assessment over a wider range than the SF-36 Role Physical scale. Patients' evaluations of the RF-CAT system were positive overall, with no differences in ratings observed between the CAT and static assessments. CONCLUSIONS: The RF-CAT was feasible, more precise than the static SF-36 RP and equally acceptable to participants as legacy measures. In empirical tests of validity, the better performance of the CAT was not uniformly statistically significant. Further research exploring the relationship between gained precision and discriminant power of the CAT assessment is needed.

Correlation of placental pathology with the postoperative outcomes and white matter injury in preterm infants following necrotizing enterocolitis.

BACKGROUND: To determine the association of placental pathologic lesions with postoperative outcomes, survival, and white matter injury (WMI) in preterm infants with NEC. METHODS: A retrospective chart review of 107 neonates with NEC (Bell stage > IIa) from Jan 2013- June 2020 was completed. Demographic, clinical, and outcome data were compared between infants with or without placental pathologic lesions. RESULTS: In this cohort, 59/107 (55%) infants had medical NEC, and 48 (45%) had surgical NEC. The infants had a mean gestational age of 28.1±3.7 weeks and a birth weight of 1103±647 g. Maternal vascular malperfusion (82/107, 76.6%) and acute histological chorioamnionitis (42, 39.3%) were the most common pathological placental lesions. Acute histologic chorioamnionitis with fetal inflammatory response was more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p = 0.02). The NEC Infants with WMI on brain MRI scans had a significantly higher incidence of acute histological chorioamnionitis (52% vs. 27.8%; P = 0.04). No significant differences in mortality, length of stay and postoperative outcomes in neonates with and without acute histologic chorioamnionitis with fetal inflammatory response were noted. On unadjusted logistic regression, acute histologic chorioamnionitis without fetal inflammatory response was also associated with higher odds of WMI (OR 2.81; 95% CI 1.05-7.54; p = 0.039). CONCLUSION: Acute histological chorioamnionitis without fetal inflammatory response was associated with higher odds of WMI in infants with NEC, with no significant impact on mortality and other postoperative outcomes.

Clinical impact of analgesic-sedative agents and peri-operative clinical status on white matter brain injury in preterm infants following surgical NEC.

BACKGROUND: The potential influence of exposure to analgesic-sedative agents (ASA) before, during, and after surgical NEC and peri-operative clinical status on white matter injury (WMI) in preterm infants has not been fully defined, and a comprehensive evaluation may inform future research and clinical interventions. METHODS: A retrospective study comparing ASA exposure before/during /after surgical NEC and peri-operative clinical status in neonates with and without WMI. RESULTS: Infants with any WMI (grade 2-4, n = 36/67, 53.7%) had a higher number of surgical procedures receiving ASA (5 [IQR: 3, 8] vs. 3 [2, 4]; p = 0.002) and had a longer duration of hypotension during their first (48.0 hours [26.0, 48.0] vs. 15.5 [6, 48]; p = 0.009) and second surgery (20 hours [0, 48h] vs. 0 [0, 22]; p = 0.017), received more hydrocortisone (35% vs.13.3%,p = 0.04) than those without any WMI. There were no differences in fentanyl/morphine/midazolam exposure before/during/after the NEC onset in the two groups.Infants with severe WMI (19/67, 28.3%, grade 3/4) had a higher incidence of AKI (P = 0.004), surgical morbidity (p = 0.047), more surgical procedures (6.5 [3, 10] vs. 4 [2, 5]; p = 0.012), and received higher mean fentanyl doses(p = 0.03) from birth until NEC onset than those without severe WMI. The univariate associations between these factors and severe WMI remained insignificant after multivariable logistic regression. CONCLUSION: Infants with WMI had more surgical procedures receiving ASA and had a longer duration of hypotension during surgeries. A large multicenter prospective study is needed to understand the full impact of ASA.

Callosal dysgenesis in fetuses with ventriculomegaly: levels of agreement between imaging modalities and postnatal outcome.

OBJECTIVE: To assess neurodevelopmental outcome of fetuses diagnosed with callosal abnormalities after referral for ventriculomegaly. METHODS: This sub-analysis of a prospective study of 430 fetuses, which were referred for ventriculomegaly and underwent sonography and magnetic resonance imaging (MRI), included those fetuses with a diagnosis of corpus callosal abnormalities after recruitment into the main study. Between three and six radiologists independently reviewed ultrasound and MR images and recorded central nervous system (CNS) abnormalities, with final diagnoses being decided by consensus. Postnatal outcomes of fetuses with callosal abnormalities were compared between those with and those without other abnormalities. RESULTS: Callosal abnormalities were detected in 13% (58/430) of the fetuses referred with ventriculomegaly. Callosal dysgenesis was isolated in 24% (14/58) of these cases, with the remainder complicated by CNS, karyotypic or other major abnormalities. Five fetuses diagnosed prenatally as having isolated callosal abnormalities had additional CNS findings on postnatal assessment. Preconference kappa for callosal abnormalities was 0.76 for ultrasound and 0.78 for MRI, indicating that these investigations had a similar level of operator dependence. Neurodevelopmental outcome was normal or showed only mild delay that resolved in 67% (8/12) children with isolated callosal abnormalities compared to 7% (2/27) in those with non-isolated callosal abnormalities (P = 0.003). CONCLUSION: Callosal abnormalities are present in a significant proportion of fetuses with a diagnosis of ventriculomegaly. Isolated callosal abnormalities are associated with normal neurodevelopmental outcome in approximately two-thirds of fetuses.

The black summer bushfires: impacts and risk factors for livestock bushfire injury in south-eastern Australia.

BACKGROUND: The 2019/2020 Australian bushfires were the largest bushfire event in modern Australian history. While actions to mitigate risk to homes from bushfires are well reported, there is very little research reported on the impacts of bushfires on livestock. With an increasing incidence of bushfires predicted, there is an urgent need to identify how farmers can best protect their livestock. OBJECTIVES: Compare bushfire affected farms with and without injured livestock to identify associations between risk factors and bushfire injury. Infer management approaches that can be used to reduce bushfire injury in livestock. METHOD: A case-control study using a structured interview questionnaire, delivered in late 2020 to cattle and sheep farmers in south-eastern Australia (New South Wales and Victoria) whose farmland was burnt in the 2019/2020 Australian bushfires. Case farms were farms with bushfires injured or killed livestock. Control farms were farms that had no bushfire injured livestock but that still had fire present on the farm. Interview responses were summarised and information theoretical approaches were used to identify potential risk factors for livestock bushfire injury and protective actions that could inform future fire-preparation recommendations. RESULTS AND DISCUSSION: Of 46 farms in the case-control study, 21 (46%) reported bushfire injured or killed livestock. Apparent protective factors identified included: preparation (having a bushfire plan and more than two farm bushfire fighting units), backburning and receiving assistance from fire authorities. Combined beef and sheep grazing enterprises appeared to have an increased risk of bushfire injury to livestock.

Early success of the arthroscopic-assisted locked loop suprapectoral biceps tenodesis.

Background: There is wide variability in surgical technique for biceps tenodesis. Prior biomechanical studies have demonstrated superior ultimate and fatigue strength with a Krakow-type locked loop when compared with simple suture and lasso-loop configurations; however, this had not yet been clinically studied. The purpose of this study was to assess the short-term results an arthroscopic-assisted locked loop (ALL) suprapectoral biceps tenodesis technique. Methods: All patients who underwent an ALL suprapectoral biceps tenodesis by a single surgeon from 2012 and 2019 with a minimum of 12-month follow-up were analyzed. Data collected included demographics, surgical indications, concomitant operative procedures, and postoperative complications of anterior shoulder "groove" pain, "Popeye deformity," biceps muscle cramping pain, and need for revision surgery. Results: Forty patients who underwent an ALL suprapectoral biceps tenodesis met inclusion criteria. Patients were 55.6 ± 8.6 years of age, consisting of 28 men (57%) and 21 women (43%). The median follow-up was 19.3 months. At the latest follow-up, 1 (2%) patient had anterior shoulder "groove" pain, and no patients had a Popeye deformity or biceps muscle cramping. There were no revision biceps tenodesis procedures. Conclusion: The ALL suprapectoral biceps tenodesis technique results in a low incidence of postoperative complications. At a short-term follow-up of 1 year, no patients had reoperations or revisions for failed biceps tenodesis. Groove pain was nearly absent in this series of patients.

Neurodevelopmental outcome of fetuses referred for ventriculomegaly.

OBJECTIVE: To characterize the delivery and postnatal neurodevelopmental outcomes of fetuses referred for ventriculomegaly (VM). METHODS: Under an internal review board-approved protocol, pregnant women were referred for magnetic resonance imaging (MRI) after sonographic diagnosis of VM and classified into one of four diagnostic groups: Group 1, normal central nervous system (CNS); Group 2, isolated mild VM (10-12 mm); Group 3, isolated VM > 12 mm; and Group 4, other CNS findings. Pregnancy outcome was obtained. Follow-up visits were offered with assessment of neurodevelopmental, adaptive and neurological functioning at 6 months and 1 year and/or 2 years of age. Atrial diameter and VM group differences in developmental outcomes were evaluated using repeated measures logistic regression and Fishers exact test, respectively. RESULTS: Of 314 fetuses, 253 (81%) were liveborn and survived the neonatal period. Fetuses in Groups 4 and 3 were less likely to progress to live delivery and to survive the neonatal period (60% and 84%, respectively) than were those in Groups 2 or 1 (93% and 100%, respectively, P < 0.001). Of the 143 fetuses followed postnatally, between 41% and 61% had a Bayley Scales of Infant Development (BSID-II) psychomotor developmental index score in the delayed range (< 85) at the follow-up visits, whereas the BSID-II mental developmental index and Vineland Adaptive Behavior composite scores were generally in line with normative expectations. Among those that were liveborn, neither VM group nor prenatal atrial diameter was related to postnatal developmental outcome. CONCLUSIONS: Diagnostic category and degree of fetal VM based on ultrasound and MRI measurements are associated with the incidence of live births and thus abnormal outcome. Among those undergoing formal postnatal testing, VM grade is not associated with postnatal developmental outcome, but motor functioning is more delayed than is cognitive or adaptive functioning.

Enhancement of endothelial cell migration and in vitro tube formation by TAP20, a novel beta 5 integrin-modulating, PKC theta-dependent protein.

Migration, proliferation, and tube formation of endothelial cells are regulated by a protein kinase C isoenzyme PKCtheta. A full-length cDNA encoding a novel 20-kD protein, whose expression was PKCtheta-dependent, was identified in endothelial cells, cloned, characterized, and designated as theta-associated protein (TAP) 20. Overexpression of TAP20 decreased cell adhesion and enhanced migration on vitronectin and tube formation in three-dimensional culture. An antiintegrin alphavbeta5 antibody prevented these TAP20 effects. Overexpression of TAP20 also decreased focal adhesion formation in alphavbeta3-deficient cells. The interaction between TAP20 and beta5 integrin cytoplasmic domain was demonstrated by protein coprecipitation and immunoblotting. Thus, the discovery of TAP20, which interacts with integrin beta5 and modulates cell adhesion, migration, and tube formation, further defines a possible pathway to angiogenesis dependent on PKCtheta.

Work pattern causes bias in self-reported activity duration: a randomised study of mechanisms and implications for exposure assessment and epidemiology.

BACKGROUND: Self-reported activity duration is used to estimate cumulative exposures in epidemiological research. OBJECTIVE: The effects of work pattern, self-reported task dullness (a measure of cognitive task demand), and heart rate ratio and perceived physical exertion (measures of physical task demands) on error in task duration estimation were investigated. METHODS: 24 participants (23-54 years old, 12 males) were randomly assigned to execute three tasks in either a continuous (three periods of 40 continuous minutes, one for each task) or a discontinuous work pattern (40 min tasks each divided into four periods of 4, 8, 12 and 16 min). Heart rate was measured during tasks. After completing the 2 h work session, subjects reported the perceived duration, dullness and physical exertion for each of the three tasks. Multivariate models were fitted to analyse errors and their absolute value to assess the accuracy in task duration estimation and the mediating role of task demands on the observed results. RESULTS: Participants overestimated the time spent shelving boxes (up to 38%) and filing journals (up to 9%), and underestimated the time typing articles (up to -22%). Over- and underestimates and absolute errors were greater in the discontinuous work pattern group. Only the self-reported task dullness mediated the differences in task duration estimation accuracy between work patterns. CONCLUSIONS: Task-related factors can affect self-reported activity duration. Exposure assessment strategies requiring workers to allocate work time to different tasks could result in biased measures of association depending on the demands of the tasks during which the exposure of interest occurs.

Sleep apnea and kidney transplant outcomes: findings from a 20-year (1997-2017) historical cohort study.

OBJECTIVE/BACKGROUND: A historic cohort single-center study of kidney transplant recipients with graft loss examined the associations between sleep apnea and two transplant outcomes, death with a functioning graft (DWFG), and graft survival time. PATIENT/METHODS: Adult patients who received transplants and experienced graft failure or DWFG from January 1, 1997 to January 1, 2017 constituted the cohort (n = 322). Data for the study were obtained by merging two secondary data sources: the Organ Procurement and Transplantation Network (OPTN) database and the transplant center's medical records. A Cox regression modeled the association of diagnosed sleep apnea, stratified by year-of transplant surgery, with graft survival time. Using backward elimination, this model was adjusted for recipient age, race/ethnicity, gender, functional status, donor age, and antigen mismatch. RESULTS: No statistically significant differences were found for proportions of DWFG in those with, versus without, sleep apnea, informing our censoring approach. When examining graft survival time, the Cox regression model was stratified given a sleep apnea and year-of-transplant interaction (p < 0.01, adjusted model). For patients transplanted between 1997 and 2008, sleep apnea was statistically significantly associated with a decreased risk of graft failure or cardiovascular-related DWFG [adjusted Hazard Ratio (aHR) = 0.63, 95%CI, 0.42-0.94]. For patients transplanted between 2009 and 2017, sleep apnea statistically significantly increased the risk of graft failure or cardiovascular-related DWFG (aHR = 2.61, 95%CI, 1.13-6.00). CONCLUSIONS: In a cohort of transplant recipients with graft loss, sleep apnea increased the risk of graft loss nearly three-fold among patients transplanted between 2009 and 2017. Similar DWFG proportions by sleep apnea presence indicate this risk is likely driven by renal failure, not mortality. Further research on whether treatment of sleep apnea can improve graft survival is warranted.

Intrinsic modifiable risk factors in ballet dancers: Applying evidence based practice principles to enhance clinical applications.

INTRODUCTION: The risk of musculoskeletal injury is multifactorial (Bahr 2005). Injury risk is a composite of intrinsic and extrinsic risk factors that can be modifiable or non-modifiable. Ballet dancers have unique risk factors, due to the nature of their art and sport. The purpose of this literature review is to identify intrinsic modifiable risk factors for injury in ballet dancers. The secondary purpose is to investigate potential screening tools which can be used to identify these risk factors. METHODS: The authors performed a review of the literature in October 2017 within the databases of MEDLINE Complete, SPORTDiscus, and PubMed Central following a list of inclusion and exclusion criteria. RESULTS: A review of the available literature identified seven intrinsic modifiable factors specifically for ballet dancers and seven appropriate screening tools. DISCUSSION: The literature identified the most common intrinsic modifiable risk factors associated with ballet dancers to be: hypermobility, fatigue, overuse, neuromuscular dysfunction, degree of turnout, weakness of core and lower extremity musculature, and lower extremity range of motion (ROM) discrepancies. CONCLUSION: Sports medicine professionals who manage these performing artists can use this literature review to help develop injury prevention programs and enhance return to sport decision.

Evaluation of a preliminary physical function item bank supported the expected advantages of the Patient-Reported Outcomes Measurement Information System (PROMIS).

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS) was initiated to improve precision, reduce respondent burden, and enhance the comparability of health outcomes measures. We used item response theory (IRT) to construct and evaluate a preliminary item bank for physical function assuming four subdomains. STUDY DESIGN AND SETTING: Data from seven samples (N=17,726) using 136 items from nine questionnaires were evaluated. A generalized partial credit model was used to estimate item parameters, which were normed to a mean of 50 (SD=10) in the US population. Item bank properties were evaluated through Computerized Adaptive Test (CAT) simulations. RESULTS: IRT requirements were fulfilled by 70 items covering activities of daily living, lower extremity, and central body functions. The original item context partly affected parameter stability. Items on upper body function, and need for aid or devices did not fit the IRT model. In simulations, a 10-item CAT eliminated floor and decreased ceiling effects, achieving a small standard error (< 2.2) across scores from 20 to 50 (reliability >0.95 for a representative US sample). This precision was not achieved over a similar range by any comparable fixed length item sets. CONCLUSION: The methods of the PROMIS project are likely to substantially improve measures of physical function and to increase the efficiency of their administration using CAT.