Accuracy of MRI in Assessment of High-Grade Partial Distal Biceps Tears.

BACKGROUND: Magnetic resonance imaging (MRI) is commonly used to diagnose and assess the extent of partial distal biceps injuries. The aim of this study was to report on the accuracy of MRI and the effect of injury history and study timing on its performance. METHODS: A retrospective review of all patients who underwent surgical treatment of partial thickness distal biceps tears at a single center by multiple surgeons was performed. Inclusion criteria consisted of the performance of a preoperative MRI and documentation of the intraoperatively visualized extent of the tear, and 68 patients met the criteria for inclusion. A chart review was completed to evaluate the symptom duration, injury history, and tear extent. RESULTS: All patients had distal biceps tears of greater than 50% intraoperatively. However, MRI did not indicate any tearing in 20 (29%) patients, and its sensitivity for high-grade tear was 44%. Magnetic resonance imaging was significantly less likely to be read as high-grade tears in patients with insidious onset of their symptoms in comparison with patients who reported a traumatic onset (27% vs 55%, P = .024). However, the time from symptom onset to MRI did not significantly correlate with diagnosis of a high-grade tear on MRI (r = -0.15, P = .21). CONCLUSIONS: These results indicate that MRI can underreport partial distal biceps tear extent, and this more commonly occurs in patients with insidious onset of pain.

The combination of PAC-1 and entrectinib for the treatment of metastatic uveal melanoma.

The treatment of metastatic uveal melanoma remains a major clinical challenge. Procaspase-3, a proapoptotic protein and precursor to the key apoptotic executioner caspase-3, is overexpressed in a wide range of malignancies, and the drug PAC-1 leverages this overexpression to selectively kill cancer cells. Herein, we investigate the efficacy of PAC-1 against uveal melanoma cell lines and report the synergistic combination of PAC-1 and entrectinib. This preclinical activity, tolerability data in mice, and the known clinical effectiveness of these drugs in human cancer patients led to a small Phase 1b study in patients with metastatic uveal melanoma. The combination of PAC-1 and entrectinib was tolerated with no treatment-related grade ≥3 toxicities in these patients. The pharmacokinetics of entrectinib were not affected by PAC-1 treatment. In this small and heavily pretreated initial cohort, stable disease was observed in four out of six patients, with a median progression-free survival of 3.38 months (95% CI 1.6-6.5 months). This study is an initial demonstration that the combination of PAC-1 and entrectinib may warrant further clinical investigation. Clinical trial registration: Clinical Trials.gov: NCT04589832.

Phase I dose-escalation study of procaspase-activating compound-1 in combination with temozolomide in patients with recurrent high-grade astrocytomas.

Background: Procaspase-3 (PC-3) is overexpressed in various tumor types, including gliomas. Targeted PC-3 activation combined with chemotherapy is a novel strategy for treating patients with high-grade gliomas, with promising preclinical activity. This study aimed to define safety and tolerability of procaspase-activating compound-1 (PAC-1) in combination with temozolomide (TMZ) for patients with recurrent high-grade astrocytomas. Methods: A modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered at increasing dose levels (DL; DL1 = 375 mg) on days 1-21, in combination with TMZ 150 mg/m2/5 days, per 28-day cycle. Dose-limiting toxicity was assessed during the first 2 cycles. Neurocognitive function (NCF) testing was conducted throughout the study. Results: Eighteen patients were enrolled (13 GBM, IDH-wild type; 2 astrocytoma, IDH-mutant, grade 3; 3 astrocytoma, IDH-mutant, grade 4). Dose escalation was discontinued after DL3 (ie, PAC-1, 625 mg) due to lack of additional funding. Grade 3 toxicity was observed in 1 patient at DL1 (elevated liver transaminases) and 1 at DL 2 (headache). Two partial responses were observed at DL1 in patients with GBM, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated. Two patients had stable disease, and 11 experienced progression. NCF testing did not show a clear relationship between PAC-1 dose, treatment duration, and declines in NCF. Conclusions: Combination of PAC-1 and TMZ was well tolerated up to 625 mg orally daily and TMZ orally 150 mg/m2/5 days per 28-day cycle. The maximum tolerated dose was not reached. Further dose escalation of PAC-1 in combination with TMZ is advised before conducting a formal prospective efficacy study in this patient population.

Clinical Outcomes of Surgical Repair for Partial Distal Biceps Tendon Tears.

PURPOSE: The purpose of this study was to describe the outcomes of patients treated with surgical repair of partial tears of the distal biceps tendon. METHODS: The study was a retrospective review of repairs of partial tears of the distal biceps tendon performed by multiple surgeons from January 1, 2015 to October 15, 2020. Inclusion criteria consisted of preoperative magnetic resonance imaging indicative of distal biceps pathology without a complete tear and surgical treatment with intraoperative confirmation of a partial tear. The presence of preceding trauma, duration of symptoms, and postoperative complications were documented. Patients were contacted for outcome assessment using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Patient-Reported Elbow Evaluation outcome measures. Clinical outcomes were obtained from 56 of 74 (76%) eligible patients with an average follow-up of 46 months (range: 15-85 months). RESULTS: After surgery, the median QuickDASH was 2.3 (interquartile range, 0-9.7), and the median Patient-Reported Elbow Evaluation score was 1 (interquartile range, 0-12). Postoperative QuickDASH scores were significantly lower than the preoperative scores. Known traumas preceding the symptoms and duration of symptoms before surgery were not significantly associated with the outcome. Of all eligible patients, 30 complications were reported in 25 (34%) patients and included 2 reruptures, 2 cases of heterotopic ossification, 1 deep infection, 1 case of implant irritation, 21 neuropraxias, and 3 hematomas. Five (7%) patients underwent 6 reoperations including 1 revision for a rerupture, 1 irrigation and debridement, 2 heterotopic ossification excisions, 1 hematoma evacuation, and 1 implant removal. CONCLUSIONS: The results suggest that the repair of partial distal biceps tendon tears is a viable treatment option with significant improvement in QuickDASH. There was no significant relationship between the postoperative outcome and duration of symptoms or known traumas preceding the symptoms. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.

BACKGROUND: Procaspase-3 (PC-3) is overexpressed in multiple tumour types and procaspase-activating compound 1 (PAC-1) directly activates PC-3 and induces apoptosis in cancer cells. This report describes the first-in-human, phase I study of PAC-1 assessing maximum tolerated dose, safety, and pharmacokinetics. METHODS: Modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered orally at 7 dose levels (DL) on days 1-21 of a 28-day cycle. Dose-limiting toxicity (DLT) was assessed during the first two cycles of therapy, and pharmacokinetics analysis was conducted on days 1 and 21 of the first cycle. Neurologic and neurocognitive function (NNCF) tests were performed throughout the study. RESULTS: Forty-eight patients were enrolled with 33 completing ≥2 cycles of therapy and evaluable for DLT. DL 7 (750 mg/day) was established as the recommended phase 2 dose, with grade 1 and 2 neurological adverse events noted, while NNCF testing showed stable neurologic and cognitive evaluations. PAC-1's t1/2 was 28.5 h after multi-dosing, and systemic drug exposures achieved predicted therapeutic concentrations. PAC-1 clinical activity was observed in patients with neuroendocrine tumour (NET) with 2/5 patients achieving durable partial response. CONCLUSIONS: PAC-1 dose at 750 mg/day was recommended for phase 2 studies. Activity of PAC-1 in treatment-refractory NET warrants further investigation. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov: NCT02355535.

Internal Fixation Construct and Defect Size Affect Healing of a Translational Porcine Diaphyseal Tibial Segmental Bone Defect.

BACKGROUND AND OBJECTIVE: Porcine translational models have become the gold-standard translational tool to study the effects of major injury and hemorrhagic shock because of their similarity to the human immunologic response to trauma. Segmental bone defects (SBDs) typically occur in warfighters with associated severe limb trauma. The purpose of this study was to develop a translational porcine diaphyseal SBD model in Yucatan minipigs (YMPs), which could be used in bone healing investigations that simulate injury-relevant conditions. We were specifically working toward developing a critical sized defect (CSD). METHODS: We used an adaptive experimental design in which both 25.0 mm and 40.0 mm SBDs were created in the tibial mid-diaphysis in skeletally mature YMPs. Initially, eight YMPs were subjected to a 25.0 mm SBD and treated with intramedullary nailing (intramedullary nail [IMN] 25mm). Due to unanticipated wound problems, we subsequently treated four specimens with identical 25.0 mm defect with dual plating (open reduction with internal fixation [ORIF] 25mm). Finally, a third group of four YMPs with 40.0 mm defects were treated with dual plating (ORIF 40mm). Monthly radiographs were made until sacrifice. Modified Radiographic Union Score for Tibia fractures (mRUST) measurements were made by three trauma-trained orthopedic surgeons. CT scans of the tibias were used to verify the union results. RESULTS: At 4 months post-surgery, mean mRUST scores were 11.7 (SD ± 1.8) in the ORIF 25mm YMPs vs. 8.5 (SD ± 1.4) in the IMN 25mm YMPs (P < .0001). All four ORIF 25mm YMPs were clinically healed. In contrast, none of the IMN 25mm YMPs were clinically healed and seven of eight IMN 25mm YMPs developed delayed wound breakdown. All four of the ORIF 40mm YMPs had flail nonunions with complete hardware failure by 3 months after surgery and were sacrificed early. CT scanning confirmed that none of the IMN 25mm YMPs, none of the ORIF 40mm YMPs, and two of four ORIF 25mm YMPs were healed. A third ORIF 25mm specimen was nearly healed on CT scanning. Inter-rater and intra-rater reliability interclass coefficients using the mRUST scale were 0.81 and 0.80, respectively. CONCLUSIONS: YMPs that had a 40 mm segment of bone removed from their tibia and were treated with dual plating did not heal and could be used to investigate interventions that accelerate bone healing. In contrast, a 25 mm SBD treated with dual plating demonstrated delayed but successful healing, indicating it can potentially be used to investigate bone healing adjuncts or conversely how concomitant injuries may impair bone healing. Pigs treated with IMN failed to heal and developed consistent delayed wound breakdown presumably secondary to chronic limb instability. The porcine YMP SBD model has the potential to be an effective translational tool to investigate bone healing under physiologically relevant injury conditions.

Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine and CDK4/6 inhibitor therapy.

PURPOSE: TTC-352 is a selective human estrogen receptor (ER) partial agonist developed for treatment of hormone-refractory ER + breast cancer. METHODS: This was an accelerated dose escalation study with the primary endpoint of maximum tolerated dose that evaluated five dose levels of TTC-352 in breast cancer progressing after at least two lines of hormonal therapy including one in combination with a CDK4/6 inhibitor. The secondary objectives were to determine treatment tolerability, pharmacokinetics of TTC-352, best response, progression-free survival (PFS), and PKCα expression in tumors. RESULTS: The study enrolled 15 patients. No dose-limiting toxicity was observed. Patients experienced the following grade 3 toxicities: asymptomatic pulmonary embolism, diarrhea, aspartate transaminase elevation, and myalgia, and one grade 4 toxicity of gamma glutamyltransferase elevation. Pharmacokinetic half-life was 7.6-14.3 h. The intra- and inter-individual variability for AUC0-∞ hampered assessment of the relationship between dose and AUC0-∞. Median PFS was 58 days (95% CI = 28,112). Higher PKCα expression in tumor stroma was associated with a trend toward longer PFS. CONCLUSIONS: TTC-352 demonstrates safety and early clinical evidence of antitumor activity against heavily pretreated hormone-refractory breast cancer. Based upon TTC-352 plasma concentrations and tolerability, the 180 mg twice a day is recommended for further testing. (ClinicalTrials.gov Identifier: NCT03201913).

Phase I Study of IGF-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R.

OBJECTIVES: Insulin-like growth factor-methotrexate (IGF-MTX) is a conjugate of methotrexate and 765IGF, a variant of IGF-1 with high affinity for insulin-like growth factor type 1 receptor. The study aim was to determine the maximum tolerated dose of IGF-MTX in refractory solid organ and hematologic malignancies expressing insulin-like growth factor type 1 receptor. MATERIALS AND METHODS: This phase I trial used a modified toxicity probability interval design with 5 cohort dose levels, and expansion cohort at maximum tolerated dose. IGF-MTX was given intravenously over 90 minutes on days 1, 8, and 15 of a 28-day cycle. RESULTS: A total of 17 patients were enrolled. The highest tolerated dose tested was 0.80 µEq/kg with dose-limiting toxicity of grade 3 hypoglycemia. Drug-related grade 3 and 4 toxicities included abdominal pain (26%), hypoglycemia (10%), and hypotension (10%). Of the 15 evaluable for response, 3 patients (20%) had stable disease, including the patient with Hodgkin lymphoma with stable disease for 12 cycles of therapy. IGF-MTX concentrations declined rapidly, with half-lives of 5.2 to 14 minutes for the initial distribution phase and 6.5 to 7.5 hours for the terminal elimination phase. Higher IGF-R1 expression did not correlate with better outcome. CONCLUSIONS: IGF-MTX is well tolerated. IGF-MTX pharmacokinetics suggest rapid cellular uptake. The activity of IGF-MTX in Hodgkin lymphoma should be explored.

The effects of spaceflight and fracture healing on distant skeletal sites.

Spaceflight results in reduced mechanical loading of the skeleton, which leads to dramatic bone loss. Low bone mass is associated with increased fracture risk, and this combination may compromise future, long-term, spaceflight missions. Here, we examined the systemic effects of spaceflight and fracture surgery/healing on several non-injured bones within the axial and appendicular skeleton. Forty C57BL/6, male mice were randomized into the following groups: (1) Sham surgery mice housed on the earth (Ground + Sham); (2) Femoral segmental bone defect surgery mice housed on the earth (Ground + Surgery); (3) Sham surgery mice housed in spaceflight (Flight + Sham); and (4) Femoral segmental bone defect surgery mice housed in spaceflight (Flight + Surgery). Mice were 9 weeks old at the time of launch and were euthanized approximately 4 weeks after launch. Micro-computed tomography (µCT) was used to evaluate standard bone parameters in the tibia, humerus, sternebra, vertebrae, ribs, calvarium, mandible, and incisor. One intriguing finding was that both spaceflight and surgery resulted in virtually identical losses in tibial trabecular bone volume fraction, BV/TV (24-28% reduction). Another important finding was that surgery markedly changed tibial cortical bone geometry. Understanding how spaceflight, surgery, and their combination impact non-injured bones will improve treatment strategies for astronauts and terrestrial humans alike.

Phase I Study of Aurora A Kinase Inhibitor Alisertib (MLN8237) in Combination With Selective VEGFR Inhibitor Pazopanib for Therapy of Advanced Solid Tumors.

OBJECTIVES: Pazopanib is a multikinase angiogenesis inhibitor. Alisertib is a highly selective inhibitor of mitotic Aurora A kinase. There is preclinical evidence that mitosis-targeting agents exhibit antiangiogenic effects. Thus, the combination of these 2 agents may have a synergistic effect on tumor vasculature. The primary objective of this study is to determine the optimal tolerated dose (OTD) for alisertib and pazopanib. MATERIALS AND METHODS: This phase 1b study evaluated the OTD of alisertib twice a day, on days 1 to 7 with pazopanib, once a day, continuously in a 21-day cycle, both taken orally. Disease response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 every 2 cycles. OTD cohort was expanded to assure safety and perform pharmacokinetics analysis. RESULTS: A total of 27 patients received treatment. Seventy-seven percent of the patients had received at least 3 prior chemotherapy regimens. Dose-limiting toxicities occurred in dose level (DL) 2+ (grade 4 thrombocytopenia and grade 3 mucositis) and DL 3 (grade 3 liver transaminases elevation and grade 3 abdominal pain). The OTD was determined to be DL 2: alisertib 20 mg twice daily and pazopanib 600 mg daily. Pharmacokinetic analysis revealed that clearance of alisertib was reduced by ∼40% in the presence of pazopanib compared with clearance in the absence of pazopanib. Fourteen patients had stable disease and 2 patients had a partial response. CONCLUSIONS: The combination of alisertib with pazopanib demonstrates manageable safety and early clinical evidence of antitumor activity in patients with advanced malignancies (NCT01639911).

Pharmacokinetics of 17 alpha hydroxyprogesterone caproate in singleton pregnancy and its influence of maternal body size measures.

BACKGROUND: Reducing spontaneous preterm deliveries is a worldwide public health priority. Although many interventions have been studied, 1 of the most effective treatments to decrease recurrent preterm birth is the use of weekly 17 alpha hydroxy progesterone caproate. Previous studies on the influence of excessive adipose tissue and obesity on the use of 17 alpha hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm deliveries have shown conflicting findings. OBJECTIVE: To estimate the pharmacokinetics of weekly17 alpha hydroxyprogesterone caproate in singleton and to evaluate the effect of maternal body size on the pharmacokinetics parameters. STUDY DESIGN: A prospective, open-label, longitudinal design was implemented for this population pharmacokinetic study. Plasma samples and clinical variables were collected in pregnant women between 16 and 36 weeks' gestational age, carrying a singleton pregnancy and receiving 17 alpha hydroxyprogesterone caproate, 250 mg intramuscularly weekly for the prevention of recurrent spontaneous preterm birth. Pharmacokinetics parameters and significant clinical covariates were estimated using mixed effect modeling. Four body size indicators were used in the model to predict pharmacokinetics parameters: lean body weight, total body weight, body mass index, and body surface area. RESULTS: A total of 56 pregnant women, aged 18-44 years with body mass index of 14.5-54.6 kg/m2, provided 114 17 alpha hydroxyprogesterone caproate plasma samples concentration for analysis. A 1-compartment model with first-order absorption satisfactorily described 17 alpha hydroxyprogesterone caproate pharmacokinetics. Compared to other body size indicators, lean body weight best explained intersubject variability. Age, race, and gestational age did not influence 17 alpha hydroxyprogesterone caproate pharmacokinetics. Lean body weight was the best descriptor for the influence of body size on 17 alpha hydroxyprogesterone caproate apparent clearance. Simulations showed that administration of a standard fixed dose of 250 mg intramuscularly produced substantially lower 17 alpha hydroxyprogesterone caproate plasma concentrations in pregnant women with body mass index >30 kg/m2 compared to those with body mass index <30 kg/m2. Conversely, adjustment of the standard dose for differences in total body weight among women resulted in markedly higher 17 alpha hydroxyprogesterone caproate concentrations in women with body mass index >30 kg/m2 compared to women with lower body mass index. Administration of doses adjusted for lean body weight produced nearly identical 117 alpha hydroxyprogesterone caproate plasma concentrations in both the low- and high-body mass index groups. CONCLUSION: Population pharmacokinetics analysis indicates the clearance significantly increases with increasing lean body mass. Higher 17 alpha hydroxyprogesterone caproate doses, adjusted by maternal lean body mass, may be required in patients with a body mass index >30 to achieve equivalent plasma concentrations in pregnant women with a body mass index <30. Adjustment of 17 alpha hydroxyprogesterone caproate doses for lean body weight produces equivalent systemic 17 alpha hydroxyprogesterone caproate exposure in pregnant women regardless of body size.

Comparative Analysis of Bibliometric, Authorship, and Collaboration Trends Over the Past 30-Year Publication History of the Journal of Orthopaedic Trauma and Injury.

OBJECTIVES: In the scientific and medical field, authorship has become increasingly important for tenure and career advancement in addition to improvement in medical care. It was the purpose of this study to investigate changes in bibliometric variables, authorship, and collaboration trends in the Journal of Orthopaedic Trauma (JOT) and Injury over a 30-year period. METHODS: A bibliometric analysis was completed for all manuscripts meeting the inclusion criteria and published throughout 1 representative year of each decade over the past 30 years. A total of 444 and 1105 manuscripts for JOT and Injury, respectively, met the inclusion criteria. Standard statistical analyses were performed with nonparametric methods for continuous variables and Pearson χ and Cochran linear trend tests for categorical variables. A P < 0.05 was considered statistically significant. RESULTS: There were significant increases over time in all bibliometric variables for both journals, except in the number of countries and pages in JOT. For JOT, the overall percentage of female first authors increased 2.3 times from 1987 to 2015 (P = 0.021). The overall percentage of female corresponding authors was 7.3%. For Injury, the overall percentage of female first authors increased 1.5 times (P = 0.007). The overall percentage of female corresponding authors was 13.1%. CONCLUSIONS: Understanding changes in publishing characteristics over time and by region is critical with the rising demands of publishing in academic medicine. JOT and Injury have showed an increase in most variables analyzed. However, female authorship in JOT is climbing at a higher rate than Injury.

Authorship trends in the Journal of Orthopaedic Research: A bibliometric analysis.

Publications are an important tool to measure one's success and achievement in academia. They can help propel a career forward and move one into a position of leadership. The overall purpose of this study was to investigate changes in bibliometric variables, authorship, and collaboration trends in the Journal of Orthopaedic Research (JOR®), since its inception in 1983. A bibliometric analysis was completed for all manuscripts meeting the inclusion criteria (638), which were published throughout the inaugural year plus one representative year of each decade. Several parameters were investigated including numbers of manuscripts, authors, collaborating institutions/countries, references, pages, and citations; region of origin and gender of authors over time and by region were main focuses. Significant increases over time were observed in all bibliometric variables analyzed except in the number of pages and citations. There was an approximate 27% point increase for both female first and corresponding authors from 1983 to 2015. While this is most likely due to the increase in the number of women that have entered the field over time, similar increases in the percentage of women holding positions on the JOR editorial board or in leadership positions within in the field may have also contributed to improvements in gender parity. Understanding changes in publishing characteristics over time, by region, and by gender are critical, especially with the rising demands of publishing in academia. JOR has seen increase in most variables analyzed, including improvements in authorship by women in the field of orthopaedic research. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3071-3080, 2018.

Bibliometric Analysis of Gender Authorship Trends and Collaboration Dynamics Over 30 Years of Spine 1985 to 2015.

STUDY DESIGN: A bibliometric analysis. OBJECTIVE: The aim of this article was to study bibliometric changes over the last 30 years of Spine. These trends are important regarding academic publication productivity. SUMMARY OF BACKGROUND DATA: Inflation in authorship number and other bibliometric variables has been described in the scientific literature. The issue of author gender is taking on increasing importance, as efforts are being made to close the gender gap. METHODS: From 1985 to 2015, 10-year incremental data for several bibliometric variables were collected, including author gender. Standard bivariate statistical analyses were performed. Trends over time were assessed by the Cochran linear trend. A P < 0.05 was considered statistically significant. RESULTS: Inclusion criteria were met for 1566 manuscripts. The majority of the manuscripts were from North America (51.2%), Europe (25.2%), and Asia (20.8%). The number of manuscripts, authors, countries, pages, and references all increased from 1985 to 2015. There was a slight increase in female first authors over time (17.5% to 18.4%, P = 0.048). There was no gender change over time for corresponding authors (14.3% to 14.0%, P = 0.29). There was an 88% increase in the percentage of female first authors having male corresponding authors (P = 0.00004), and a 123% increase in male first authors having female corresponding authors (P = 0.0002). The 14% to 18% of female authors in Spine is higher than the ∼5% female membership of the Scoliosis Research Society and North American Spine Society. CONCLUSION: Manuscripts in Spine over the past 30 years have shown a significant increase in the number of authors, collaborating institutions and countries, printed pages, references, and number of times each manuscript was cited. There has been a mild increase in female first authorship, but none in corresponding authorship. Increases in female authorship will likely require recruitment of more females into the discipline rather than providing females in the discipline with authorship opportunities. LEVEL OF EVIDENCE: N/A.

Historical Analysis of Bibliometric Trends in the Journal of Pediatric Orthopaedics With a Particular Focus on Sex.

BACKGROUND: Orthopaedics is the clinical discipline with the lowest percentage of female residents and faculty. Pediatric orthopaedics has a higher percentage of women than other orthopaedic subspecialties. It was the purpose of this study to examine bibliometric trends in the Journal of Pediatric Orthopaedics (JPO) with a specific focus on sex. METHODS: A bibliometeric analysis for the years 2015, 2005, 1995, 1985, 1981 was performed. The names of first and corresponding authors; corresponding author position; country of origin; number of institutions, countries, authors, printed pages, and references was tabulated. Author sex was identified for the first and corresponding authors using the "Baby Name Guesser" (www.gpeters.com/names/baby-names.php). A P<0.05 was considered significant. RESULTS: There were 746 publications; 68.7% were from North America. The average number of authors, corresponding author position, collaborating institutions, countries, and number of references increased, whereas the number of printed pages decreased. Asia had the greatest number of authors (4.4), with Australia/New Zealand the fewest (3.4). Sex was determined for 98.3% of the first authors and 98.5% of the corresponding authors. There was a significant increase in the number of female first authors over time (5.9% to 25.6%, P<10), especially in Europe and North America. There were significant increase in the number of female corresponding authors over time (5.8% to 17.6%, P=0.000009). There was a significant trend to have a greater percentage of both female first and corresponding authors over time (P=0.0005) with a reverse trend for both male first and corresponding authors (P<10). CONCLUSIONS: In this study, we noted that the number of female first and corresponding authors in Journal of Pediatric Orthopaedics has been steadily increasing. This should result in more female pediatric orthopaedic surgeons in academic faculty positions.

Bibliometric analysis of authorship trends and collaboration dynamics over the past three decades of BONE's publication history.

The existence of a gender gap in academia has been a hotly debated topic over the past several decades. It has been argued that due to the gender gap, it is more difficult for women to obtain higher positions. Manuscripts serve as an important measurement of one's accomplishments within a particular field of academia. Here, we analyzed, over the past 3 decades, authorship and other trends in manuscripts published in BONE, one of the premier journals in the field of bone and mineral metabolism. For this study, one complete year of manuscripts was evaluated (e.g. 1985, 1995, 2005, 2015) for each decade. A bibliometric analysis was then performed of authorship trends for those manuscripts. Analyzed fields included: average number of authors per manuscript, numerical position of the corresponding author, number of institutions collaborating on each manuscript, number of countries involved with each manuscript, number of references, and number of citations per manuscript. Each of these fields increased significantly over the 30-year time frame (p<10-6). The gender of both the first and corresponding authors was identified and analyzed over time and by region. There was a significant increase in the percentage of female first authors from 23.4% in 1985 to 47.8% in 2015 (p=0.001). The percentage of female corresponding authors also increased from 21.2% in 1985 to 35.4% in 2015 although it was not significant (p=0.07). With such a substantial emphasis being placed on publishing in academic medicine, it is crucial to comprehend the changes in publishing characteristics over time and geographical region. These findings highlight authorship trends in BONE over time as well as by region. Importantly, these findings also highlight where challenges still exist.

Bibliometric Analysis of Female Authorship Trends and Collaboration Dynamics Over JBMR's 30-Year History.

In academia, authorship is considered a currency and is important for career advancement. As the Journal of Bone and Mineral Research (JBMR) is the highest-ranked journal in the field of bone, muscle, and mineral metabolism and is the official publication of the American Society for Bone and Mineral Research, we sought to examine authorship changes over JBMR's 30-year history. Two bibliometric methods were used to collect the data. The "decade method" included all published manuscripts throughout 1 year in each decade over the past 30 years starting with the inaugural year, yielding 746 manuscripts for analysis. The "random method" examined 10% of published manuscripts from each of the 30 years, yielding 652 manuscripts for analysis. Using both methods, the average number of authors per manuscript, numerical location of the corresponding author, number of collaborating institutions, number of collaborating countries, number of printed manuscript pages, and the number of times each manuscript was cited all significantly increased between 1986 and 2015 (p < 10-4 ). Using the decade method, there was a significant increase in the percentage of female first authors over time from 35.8% in 1986 to 47.7% in 2015 (p = 0.02), and this trend was confirmed using the random method. The highest percentage of female first authors in 2015 was in Europe (60.0%), and Europe also had the most dramatic increase in female first authors over time (more than double in 2015 compared with 1986). Likewise, the overall number of female corresponding authors significantly increased during the past 30 years. With the increasing demands of publishing in academic medicine, understanding changes in publishing characteristics over time and by geographical region is important. These findings highlight JBMR's authorship trends over the past 30 years and demonstrate those countries having the most changes and where challenges still exist. © 2017 American Society for Bone and Mineral Research.

Eprinomectin pour-on (EPRINEX® Pour-on, Merial): efficacy against gastrointestinal and pulmonary nematodes and pharmacokinetics in sheep.

BACKGROUND: The anthelmintic efficacy of the 0.5% w/v topical formulation of eprinomectin (EPN), EPRINEX® Pour-on (Merial) when administered at 1 mg/kg body weight was evaluated in sheep in two dose confirmation laboratory studies and one multicenter field study. In addition, the pharmacokinetics of EPN when administered at that dosage to adult sheep was determined. RESULTS: In the two dose confirmation studies, which included 10 sheep each, sheep treated with topical EPN had significantly (p < 0.05) fewer of the following nematodes than the untreated sheep with overall reduction of nematode counts by >99%: adult Dictyocaulus filaria, Haemonchus contortus, Teladorsagia circumcincta(pinnata/trifurcata), Trichostrongylus axei, T. colubriformis, T. vitrinus, Cooperia curticei, Nematodirus battus, Strongyloides papillosus, Chabertia ovina and Oesophagostomum venulosum, and inhibited fourth-stage Teladorsagia larvae. A total of 196 sheep harboring naturally acquired gastrointestinal nematode infections were included in the field efficacy study at two sites each in Germany (48 Merino x Ile de France lambs, 52 adult Merino females) and in Italy (adult male and female Bagnolese, Lacaune, Lacaune x Bagnolese, Bagnolese x Sarda sheep; 48 animals per site). Animals were blocked on pre-treatment body weight and within each block, one animal was randomly assigned to the control (untreated) group and three animals were randomly assigned to be treated with topical EPN. Examination of feces 14 days after treatment demonstrated that, relative to the controls, topical EPN-treated sheep had significantly (p < 0.0001) lower strongylid egg counts. Reduction was ≥97% at each site and 98.6% across all sites. Pharmacokinetics of EPN following single treatment with topical EPN were determined in eight ~4.5 year old female Merino cross sheep based on the analysis of plasma samples which were collected from two hours to 21 days following treatment. The main pharmacokinetic parameters were: Cmax 6.20 ± 1.71 ng/mL, AUClast 48.8 ± 19.2 day*ng/mL, Tmax 3.13 ± 2.99 days and T1/2 6.40 ± 2.95 days. No treatment-related health problems or adverse drug events were observed in any study. CONCLUSION: These studies demonstrated 0.5% w/v EPN administered topically at 1 mg/kg body weight to be highly efficacious against a broad range of ovine gastrointestinal nematodes and D. filaria lungworms and well tolerated by sheep of different ages, breeds, gender and physiological status.

Effects of Regulatory Support Services on Institutional Review Board Turnaround Times.

We evaluated how regulatory support services provided by University of Illinois at Chicago's Center for Clinical and Translational Science may reduce Institutional Review Board (IRB) turnaround times. IRB applications were categorized by receipt of any regulatory support and amount of support received. Turnaround time included total turnaround time, time for IRB review, and time for investigators to modify protocols. There were no differences in any turnaround times for supported versus nonsupported applications. However, for supported applications, those receiving more intensive support had total turnaround times 16.0 days ( SE 7.62, p < .05) faster than those receiving less intensive support. Receiving higher regulatory support may be associated with faster approval of IRB submissions.