Randomised, Phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer.

INTRODUCTION: Cisplatin and gemcitabine (CisGem) are standard chemotherapy for advanced biliary tract cancer (BTC). The MEK inhibitor selumetinib showed synergy with gemcitabine when administered sequentially in BTC. This randomised Phase 2 trial aimed to assess the efficacy of sequential or continuous selumetinib with CisGem. METHODS: Patients with advanced BTC received CisGem; arm A included selumetinib every day, arm B: selumetinib, days 1-5, 8-19 each cycle. Arm C received CisGem alone. Selumetinib was dosed at 75 mg BID but amended to 50 mg BID due to toxicity. RESULTS: In all, 51 participants were evaluable for response. No significant difference was seen in mean change in tumour size at 10 weeks between arms A and C (-7.8% vs -12.8%, P = 0.54) or arms B and C (-15% vs -12.8%, P = 0.78). There was no difference in median progression-free survival (6.0, 7.0, 6.3 months, P > 0.95) or overall survival (11.7, 11.7, 12.8 months, P = 0.70) for arms A, B and C, respectively. More participants experienced grade 3-4 toxicities in selumetinib-containing arms. More participants in arm A required chemotherapy dose reductions (P = 0.01) with lower chemotherapy dose intensity during the first 10 weeks. CONCLUSION: Adding sequential or continuous selumetinib to CisGem failed to improve efficacy and increased toxicity in patients with advanced BTC.

Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial.

BACKGROUND: Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. METHODS: Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. RESULTS: In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. CONCLUSIONS: This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013.

Similar Functional Gains Using Radial Versus Combined Shockwave Therapy in Management of Plantar Fasciitis.

Plantar fasciitis is a common condition that causes foot pain. While shockwave therapy has been shown to provide successful results, comparative outcomes from different forms of shockwave therapy have yet to be described for this condition. In this retrospective cohort study, we describe findings from a quality improvement initiative assessing safety and functional outcomes for patients with plantar fasciitis treated with radial shockwave therapy (n = 20) or radial and focused shockwave therapy (combined shockwave, n = 18). Most were runners (n = 31, 81.6%), mean age was 43.3 ± 12.9 years, and average symptom duration 12.1 ± 11.1 months. All patients were prescribed an exercise program focusing on foot intrinsic strengthening. We hypothesized both groups would have improvement in function using the foot and Ankle Ability Measure, with a similar safety profile. Both radial and combined groups received similar number of total treatments (4.9 ± 2.5 and 4.1 ± 2.4, respectively; p = .33). Within group score changes for the Activities of Daily Living and Sports subscales were observed for both the radial (16.5 ± 16.3, p < .001; 31.7 ± 23.1, p < .001) and combined groups (19.8 ± 10.8, p = .001; 26.0 ± 21.5, p = .003). There was no difference in proportion of patients meeting the minimal clinically important difference between radial and combined groups regarding the Activities of Daily Living (14 (70%) vs 14 (77.8%), p = .58) and Sports subscales (17 (85%) vs 12 (75%), p = .45). Collectively, these findings suggest that a majority of patients with chronic plantar fasciitis may achieve functional gains using either form of shockwave therapy.

Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2.

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion. Twelve metastatic melanoma patients were treated with non-myeloablative lymphodepleting chemotherapy, TIL, and low-dose subcutaneous IL-2 (125,000 IU/kg/day, maximum 9-10 doses over 2 weeks). All but one patient had previously progressed after treatment with immune checkpoint inhibitors. No unexpected adverse events were observed, and patients received an average of 6.8 doses of IL-2. By RECIST v1.1, two patients experienced a partial response, one patient had an unconfirmed partial response, and six had stable disease. Biomarker assessment confirmed an increase in IL-15 levels following lymphodepleting chemotherapy as expected and a lack of peripheral regulatory T-cell expansion following protocol treatment. Interrogation of the TIL infusion product and monitoring of the peripheral blood following infusion suggested engraftment of TIL. In one responding patient, a population of T cells expressing a T-cell receptor Vß chain that was dominant in the infusion product was present at a high percentage in peripheral blood more than 2 years after TIL infusion. This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.).

An N-terminal heterozygous missense CASK mutation is associated with microcephaly and bilateral retinal dystrophy plus optic nerve atrophy.

Heterozygous loss-of-function mutations in the X-linked gene CASK are associated with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) and ophthalmological disorders including optic nerve atrophy (ONA) and optic nerve hypoplasia (ONH). Recently, we have demonstrated that CASK(+/-) mice display ONH with 100% penetrance but exhibit no change in retinal lamination or structure. It is not clear if CASK loss-of-function predominantly affects retinal ganglion cells, or if other retinal cells like photoreceptors are also involved. Here, we report a heterozygous missense mutation in the N-terminal calcium/calmodulin-dependent kinase (CaMK) domain of the CASK protein in which a highly conserved leucine is mutated to the cyclic amino acid proline. In silico analysis suggests that the mutation may produce destabilizing structural changes. Experimentally, we observe pronounced misfolding and insolubility of the CASKL209P protein. Interestingly, the remaining soluble mutant protein fails to interact with Mint1, which specifically binds to CASK's CaMK domain, suggesting a mechanism for the phenotypes observed with the CASKL209P mutation. In addition to microcephaly, cerebellar hypoplasia and delayed development, the subject with the L209P mutation also presented with bilateral retinal dystrophy and ONA. Electroretinography indicated that rod photoreceptors are the most prominently affected cells. Our data suggest that the CASK interactions mediated by the CaMK domain may play a crucial role in retinal function, and thus, in addition to ONH, individuals with mutations in the CASK gene may exhibit other retinal disorders, depending on the nature of mutation.

Medical Rehabilitation: Guidelines to Advance the Field With High-Impact Clinical Trials.

The purpose of this Special Communication is to summarize guidelines and recommendations stemming from an expert panel convened by the National Institutes of Health, National Center for Medical Rehabilitation Research (NCMRR) for a workshop entitled The Future of Medical Rehabilitation Clinical Trials, held September 29-30, 2016, at the NCMRR offices in Bethesda, Maryland. The ultimate goal of both the workshop and this summary is to offer guidance on clinical trials design and operations to the medical rehabilitation research community, with the intent of maximizing the effect of future trials.

Multiple Treatments of Pediatric Constraint-Induced Movement Therapy (pCIMT): A Clinical Cohort Study.

Pediatric constraint-induced movement therapy (pCIMT) is one of the most efficacious treatments for children with cerebral palsy (CP). Distinctive components of pCIMT include constraint of the less impaired upper extremity (UE), high-intensity therapy for the more impaired UE (≥ 3 hr/day, many days per week, for multiple weeks), use of shaping techniques combined with repetitive task practice, and bimanual transfer. A critical issue is whether multiple treatments of pCIMT produce additional benefit. In a clinical cohort (mean age = 31 mo) of 28 children with asymmetrical CP whose parents sought multiple pCIMT treatments, the children gained a mean of 13.2 (standard deviation [SD] = 4.2) new functional skills after Treatment 1; Treatment 2 produced a mean of 7.3 (SD = 4.7) new skills; and Treatment 3, 6.5 (SD = 4.2). These findings support the conclusion that multiple pCIMT treatments can produce clinically important functional gains for children with hemiparetic CP.

Pulsed electromagnetic fields potentiate neurite outgrowth in the dopaminergic MN9D cell line.

Pulsed electromagnetic fields (PEMF) exert biological effects and are in clinical use to facilitate bone repair and wound healing. Research has demonstrated that PEMF can induce signaling molecules and growth factors, molecules that play important roles in neuronal differentiation. Here, we tested the effects of a low-amplitude, nonthermal, pulsed radiofrequency signal on morphological neuronal differentiation in MN9D, a dopaminergic cell line. Cells were plated in medium with 10% fetal calf serum. After 1 day, medium was replaced with serum-containing medium, serum-free medium, or medium supplemented with dibutyryl cyclic adenosine monophosphate (Bt2 cAMP), a cAMP analog known to induce neurite outgrowth. Cultures were divided into groups and treated with PEMF signals for either 30 min per day or continuously for 15 min every hour for 3 days. Both serum withdrawal and Bt2 cAMP significantly increased neurite length. PEMF treatment similarly increased neurite length under both serum-free and serum-supplemented conditions, although to a lesser degree in the presence of serum, when continuous treatments had greater effects. PEMF signals also increased cell body width, indicating neuronal maturation, and decreased protein content, suggesting that this treatment was antimitotic, an effect reversed by the inhibitor of cAMP formation dideoxyadenosine. Bt2 cAMP and PEMF effects were not additive, suggesting that neurite elongation was achieved through a common pathway. PEMF signals increased cAMP levels from 3 to 5 hr after treatment, supporting this mechanism of action. Although neuritogenesis is considered a developmental process, it may also represent the plasticity required to form and maintain synaptic connections throughout life.

Patient-reported outcomes during telehealth versus in-person follow-up visits for patients treated with extracorporeal shockwave therapy.

BACKGROUND: The limited research describing clinical outcomes using telehealth for management of musculoskeletal conditions is primarily within orthopedic surgery care. OBJECTIVE: To characterize differences in patient reported outcomes using telehealth compared with in-person follow-up visits in patients with Achilles tendinopathy (AT) or plantar fasciitis (PF) treated using extracorporeal shockwave therapy (ESWT). DESIGN: Retrospective chart review. SETTING: Outpatient sports medicine clinic. PATIENTS: 82 patients with AT and 46 patients with PF. INTERVENTIONS: In-person (n = 76) and telehealth (n = 52) follow-up visits. MAIN OUTCOME MEASUREMENTS: Victorian Institute of Sports Assessment-Achilles (VISA-A) for AT and Foot and Ankle Ability Measure (FAAM) for PF as well as billing level. RESULTS: There was significant improvement from baseline to final VISA-A (p < .01) and FAAM (p < .01) following ESWT. No significant difference existed in the proportion of patients who met the minimal clinically important difference based on in-person (71.1%) versus telehealth (71.2%) follow-up (p = .99). The in-person group demonstrated higher billing levels compared to the telehealth group (Level: 3.5 ± 0.6 vs. 2.8 ± 0.7, p < .01). CONCLUSIONS: Given no significant differences in outcomes between two modes of follow-ups, telehealth may serve as an alternative method to guide management of musculoskeletal injuries with ESWT and other procedures.

The effect of constraint-induced movement therapy for children with hemiplegic cerebral palsy in Vietnam.

PURPOSE: Pediatric constraint-induced movement therapy (CIMT) is an evidence-based treatment that has a long history of demonstrating efficacy for children with hemiparesis. The purpose of this study is to determine the effectiveness of a culturally responsive CIMT program for children with hemiplegic cerebral palsy (CP) developed for the Vietnam healthcare system. METHODS: Thirty children with hemiplegic CP (mean age = 2.88 years, age range: 1 to 8 yrs, 60% male) were recruited to a CIMT program (7.5 h/week, 4 weeks) developed for the cultural context of Vietnam. Motor abilities of the affected arm and participation in daily activities were evaluated at 3 time points (one-week prior to CIMT (baseline), one-week before (pre) and after (post) CIMT) using the Quality of Upper Extremity Skill Test (QUEST) and Pediatric Motor Activity Log-Revised (PMAL-R). Individual goals were measured using the Goal Attainment Scale (GAS). RESULTS: There were significant increases in the "How often scale" and "How Well" scales of the PMAL-R (0.75 and 0.75, p < 0.00)). Score of Grasp and Dissociated Movement items on the QUEST increased significantly (6.47 and 7.63, p < 0.001). Group GAS T-Scores were 52.19 indicating that children met individual goals. CONCLUSIONS: A model of CIMT was successfully developed and delivered within the Vietnamese healthcare system. Future studies should explore the optimal model for CIMT in various regions of world where the delivery of rehabilitation services may vary.

This is the first study to investigate the effectiveness of a pediatric constraint-induced movement therapy (PCIMT), which was specially designed to be contextually and culturally relevant for Vietnam.The program was delivered by trained therapists and parents educated about the essential elements of PCIMT.The results provide important guidance on how to adapt current evidence-based components of PCIMT models to meet the needs of children globally in settings where culture, values, and models of healthcare may differ.Future global studies on PCIMT should continue to explore the optimal implementation model for CIMT to support all children with unilateral motor weakness in various regions of the world where the delivery of rehabilitation services may vary.

Ligand-mimicking receptor variant discloses binding and activation mode of prolactin-releasing peptide.

The prolactin-releasing peptide receptor and its bioactive RF-amide peptide (PrRP20) have been investigated to explore the ligand binding mode of peptide G-protein-coupled receptors (GPCRs). By receptor mutagenesis, we identified the conserved aspartate in the upper transmembrane helix 6 (Asp(6.59)) of the receptor as the first position that directly interacts with arginine 19 of the ligand (Arg(19)). Replacement of Asp(6.59) with Arg(19) of PrRP20 led to D6.59R, which turned out to be a constitutively active receptor mutant (CAM). This suggests that the mutated residue at the top of transmembrane helix 6 mimics Arg(19) by interacting with additional binding partners in the receptor. Next, we generated an initial comparative model of this CAM because no ligand docking was required, and we selected the next set of receptor mutants to find the engaged partners of the binding pocket. In an iterative process, we identified two acidic residues and two hydrophobic residues that form the peptide ligand binding pocket. As all residues are localized on top or in the upper part of the transmembrane domains, we clearly can show that the extracellular surface of the receptor is sufficient for full signal transduction for prolactin-releasing peptide, rather than a deep, membrane-embedded binding pocket. This contributes to the knowledge of the binding of peptide ligands to GPCRs and might facilitate the development of GPCR ligands, but it also provides new targeting of CAMs involved in hereditary diseases.

The activity of prolactin releasing peptide correlates with its helicity.

The prolactin releasing peptide (PrRP) is involved in regulating food intake and body weight homeostasis, but molecular details on the activation of the PrRP receptor remain unclear. C-terminal segments of PrRP with 20 (PrRP20) and 13 (PrRP8-20) amino acids, respectively, have been suggested to be fully active. The data presented herein indicate this is true for the wildtype receptor only; a 5-10-fold loss of activity was found for PrRP8-20 compared to PrRP20 at two extracellular loop mutants of the receptor. To gain insight into the secondary structure of PrRP, we used CD spectroscopy performed in TFE and SDS. Additionally, previously reported NMR data, combined with ROSETTANMR, were employed to determine the structure of amidated PrRP20. The structural ensemble agrees with the spectroscopic data for the full-length peptide, which exists in an equilibrium between α- and 3(10)-helix. We demonstrate that PrRP8-20's reduced propensity to form an α-helix correlates with its reduced biological activity on mutant receptors. Further, distinct amino acid replacements in PrRP significantly decrease affinity and activity but have no influence on the secondary structure of the peptide. We conclude that formation of a primarily α-helical C-terminal region of PrRP is critical for receptor activation.

Evidence for Using ACQUIRE Therapy in the Clinical Application of Intensive Therapy: A Framework to Guide Therapeutic Interactions.

Intensive therapies have become increasingly popular for children with hemiparesis in the last two decades and are specifically recommended because of high levels of scientific evidence associated with them, including multiple randomized controlled trials and systematic reviews. Common features of most intensive therapies that have documented efficacy include: high dosages of therapy hours; active engagement of the child; individualized goal-directed activities; and the systematic application of operant conditioning techniques to elicit and progress skills with an emphasis on success-oriented play. However, the scientific protocols have not resulted in guiding principles designed to aid clinicians with understanding the complexity of applying these principles to a heterogeneous clinical population, nor have we gathered sufficient clinical data using intensive therapies to justify their widespread clinical use beyond hemiparesis. We define a framework for describing moment-by-moment therapeutic interactions that we have used to train therapists across multiple clinical trials in implementing intensive therapy protocols. We also document outcomes from the use of this framework during intensive therapies provided clinically to children (7 months-20 years) from a wide array of diagnoses that present with motor impairments, including hemiparesis and quadriparesis. Results indicate that children from a wide array of diagnostic categories demonstrated functional improvements.

Dietary Supplement Intake and Factors Associated with Increased Use in Preadolescent Endurance Runners.

BACKGROUND: The prevalence of dietary supplement intake among preadolescent endurance runners is currently unknown. OBJECTIVE: Our aim was to describe use of dietary supplements, higher-risk supplements, and sport foods among preadolescent endurance athletes and identify associated characteristics of dietary supplement users in this population. DESIGN: This was a retrospective, cross-sectional study. PARTICIPANTS/SETTING: Participants were 2,113 preadolescent endurance runners (male: n = 1,255, female: n = 858; mean age ± standard deviation = 13.2 ± 0.9 years). MAIN OUTCOME MEASURES: Use of dietary supplements, higher-risk dietary supplements, and sport foods on 2 or more days per week during the past year. STATISTICAL ANALYSES PERFORMED: Mann-Whitney U tests, χ2 tests, univariate and multivariate analyses. RESULTS: Twenty-six percent (n = 551) of preadolescent runners used dietary supplements on 2 or more days per week during the past year; 1.3% (n = 27) reported taking higher-risk supplements. Compared with male runners, female runners reported higher use of 1 or more supplements (32.5% vs 21.7%; P < .001) and 4 or more supplements (4.0% vs 1.9%; P = 0.005), multivitamin/minerals (24.2% vs 14.4%; P < .001), vitamin D (12.4% vs 5.6%; P < .001), calcium (8.9% vs 4.8%; P < .001), iron (3.1 vs 1.1%; P < .001), probiotic supplements (8.2% vs 1.3%; P < .001), and diet pills (0.5% vs 0.0%; P = .02). Male runners reported higher use of creatine (1.3% vs 0.0%; P < .001) and sport foods, including protein bars and drinks (19.5% vs 8.4%; P < .001), energy bars (23.5% vs 9.7%; P < .001), and carbohydrate-electrolyte drinks (27.9% vs 13.3%; P < .001) than female runners. Factors independently associated with a higher likelihood for dietary supplement use included weight loss in the past year, female (vs male) gender, following a vegetarian diet, skipping meals, attempting to gain weight, and history of a running-related bone stress injury. CONCLUSIONS: More than one-quarter of preadolescent runners regularly consumed dietary supplements. Behaviors consistent with dietary restriction and history of bone stress injury were associated with higher likelihood for supplement use. Further work to understand supplement use patterns and potential value for nutrition education is advised to optimize health of preadolescent runners.

Running-related injuries in middle school cross-country runners: Prevalence and characteristics of common injuries.

BACKGROUND: Understanding the prevalence and factors associated with running-related injuries in middle school runners may guide injury prevention. OBJECTIVE: To determine the prevalence of running-related injuries and describe factors related to a history of injury. DESIGN: Retrospective cross-sectional study. SETTING: Survey distributed online to middle school runners. METHODS: Participants completed a web-based survey regarding prior running-related injuries, training, sleep, diet, and sport participation. MAIN OUTCOME MEASUREMENTS: Prevalence and characteristics differentiating girls and boys with and without running-related injury history adjusted for age. PARTICIPANTS: Youth runners (total: 2113, average age, 13.2 years; boys: n = 1255, girls: n = 858). RESULTS: Running-related injuries were more prevalent in girls (56% vs. 50%, p = .01). Ankle sprain was the most common injury (girls: 22.5%, boys: 21.6%), followed by patellofemoral pain (20.4% vs. 7.8%) and shin splints (13.6% vs. 5.9%); both were more prevalent in girls (p < .001). Boys more frequently reported plantar fasciitis (5.6% vs. 3.3%, p = .01), iliotibial band syndrome (4.1% vs. 1.4%, p = .001) and Osgood-Schlatter disease (3.8% vs. 1.2%, p = .001). Runners with history of running-related injuries were older, ran greater average weekly mileage, ran faster, had fewer average hours of sleep on weekends, skipped more meals, missed breakfast, and consumed less milk (all p < .05). Girls with history of running-related injuries reported higher dietary restraint scores, later age of menarche, more menstrual cycle disturbances, and higher likelihood of following vegetarian diets and an eating disorder diagnosis (all p < .05). Runners with no history of running-related injuries were more likely to have participated in ≥2 years of soccer or basketball (p < .001). CONCLUSIONS: Most middle school runners reported a history of running-related injuries and certain injuries differing by gender. Modifiable factors with the greatest association with running-related injuries included training volume, dietary restraint, skipping meals, and less sleep. Sport sampling, including participation in ball sports, may reduce running-related injury risk in this population.

Prevalence and factors associated with bone stress injury in middle school runners.

BACKGROUND: Bone stress injury (BSI) in youth runners is clinically important during times of skeletal growth and is not well studied. OBJECTIVE: To evaluate the prevalence, anatomical distribution, and factors associated with running-related BSI in boy and girl middle school runners. DESIGN: Retrospective cross-sectional study. SETTING: Online survey distributed to middle school runners. METHODS: Survey evaluated BSI history, age, grade, height, weight, eating behaviors, menstrual function, exercise training, and other health characteristics. MAIN OUTCOME MEASUREMENTS: Prevalence and characteristics associated with history of BSI, stratified by cortical-rich (eg, tibia) and trabecular-rich (pelvis and femoral neck) locations. PARTICIPANTS: 2107 runners (n = 1250 boys, n = 857 girls), age 13.2 ± 0.9 years. RESULTS: One hundred five (4.7%) runners reported a history of 132 BSIs, with higher prevalence in girls than boys (6.7% vs 3.8%, p = .004). The most common location was the tibia (n = 51). Most trabecular-rich BSIs (n = 16, 94% total) were sustained by girls (pelvis: n = 6; femoral neck: n = 6; sacrum: n = 4). In girls, consuming <3 daily meals (odds ratio [OR] = 18.5, 95% confidence interval [CI] = 7.3, 47.4), eating disorder (9.8, 95% CI = 2.0, 47.0), family history of osteoporosis (OR = 6.9, 95% CI = 2.6, 18.0), and age (OR = 1.6, 95% CI = 1.0, 2.6) were associated with BSI. In boys, family history of osteoporosis (OR = 3.2, 95% CI = 1.2, 8.4), prior non-BSI fracture (OR = 3.2, 95% CI = 1.6, 6.7), and running mileage (OR = 1.1, 95% CI = 1.0, 1.1) were associated with BSI. Participating in soccer or basketball ≥2 years was associated with lower odds of BSI for both sexes. CONCLUSION: Whereas family history of osteoporosis and prior fracture (non-BSI) were most strongly related to BSI in the youth runners, behaviors contributing to an energy deficit, such as eating disorder and consuming <3 meals daily, also emerged as independent factors associated with BSI. Although cross-sectional design limits determining causality, our findings suggest promoting optimal skeletal health through nutrition and participation in other sports including soccer and basketball may address factors associated with BSI in this population.

Pilot Study on the Use of a Video-Based Metric Goal Attainment Assessment.

The scientific investigation of developmental neurorehabilitation has been negatively impacted by a lack of outcome measures sensitive to interventional effect, and is currently in need of assessment measures that can be used during social distancing protocols. Here we report on the usability and feasibility from a pilot test of a novel assessment methodology. This preliminary data demonstrate the usability and feasibility of this assessment system, suggests that it is sensitive to change, and supports the further development and testing of this assessment. The assessment methodology, here presented, generates a percent change score based on the metric measurement of individualized goals before and after intervention, thereby facilitating comparisons between groups and across goals. Moreover, it can be conducted remotely and introduces the novel element of goal appropriacy assessment such that goal selection, as well as goal attainment, are assessed via metric measurement.

A Narrative Review Evaluating Extracorporeal Shockwave Therapy as a Potential Regenerative Treatment for Musculoskeletal Conditions in Military Personnel.

INTRODUCTION: Extracorporeal shockwave therapy (ESWT) has a wide variety of clinical applications ranging from urology to orthopedics. Extracorporeal shockwave therapy is of particular interest to military medicine in the treatment of diverse musculoskeletal injuries, including recalcitrant tendinopathy. Much of the evidence for ESWT is from studies in the civilian population, including athletes. A few investigations have been conducted within military personnel. Musculoskeletal conditions within military personnel may contribute to pain and physical limitations. Optimal functional outcomes could be achieved through ESWT. The purpose of this narrative review is to summarize the current evidence on the efficacy of ESWT the in management of lower extremity musculoskeletal injuries in the military. Further, we explore the relative efficacy of ESWT compared to regenerative medicine procedures, including studies with treatment using platelet-rich plasma. MATERIALS AND METHODS: A literature review was performed in April 2020 to identify studies evaluating the use of ESWT for lower extremity conditions commonly observed in military personnel, including plantar fasciitis, Achilles tendinopathy, patellar tendinopathy, medial tibial stress syndrome, and knee arthritis. The literature search was completed by two researchers independently, using PubMed and Embase databases and same search terms. Disagreements were adjudicated by a senior author. Due to the paucity of relevant search results, the search term parameters were expanded to incorporate active participants. RESULTS: Two studies evaluated the use of ESWT in a military population for lower extremity injuries. This included a randomized control trial in active military with medial tibial stress syndrome and an unblinded retrospective study for the chronic plantar fasciitis condition. Both studies in the military had favorable outcomes in the use of ESWT compared to other treatment arms. The remaining studies predominantly included athletes. Although heterogeneity on the quality of the studies may prevent meta-analysis and limit the generalization of the findings, the majority of studies demonstrated an improvement in pain and return to activity using ESWT. Two studies using platelet-rich plasma as a treatment arm identified similar short-term outcomes compared to ESWT for Achilles tendinopathy and patellar tendinopathy. CONCLUSION: Our findings suggest that ESWT is a safe and well-tolerated intervention with positive outcomes for lower extremity conditions commonly seen in the military. The few studies comparing ESWT to PRP suggest regenerative benefits similar to orthobiologics in the shorter term. More robust quality designed research may enable the evaluation of ESWT efficacy within the military population. In summary, the use of ESWT may provide pain reduction and improved function in active populations with lower extremity musculoskeletal injuries. Further research in the military is needed to evaluate shockwave efficacy in order to advance musculoskeletal care and improve outcomes.