Search

On December 16, 2020, the FDA granted regular approval to margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with HER2-positive (HER2+) metastatic breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Approval was based on data from SOPHIA, a multicenter, randomized, open-label, active controlled study comparing margetuximab with trastuzumab, in combination with chemotherapy. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review. SOPHIA demonstrated a 0.9-month difference in median PFS between the two treatment arms [5.8 vs. 4.9 months, respectively; stratified HR, 0.76 (95% confidence interval: 0.59–0.98; P = 0.0334)]. Overall survival (OS) was immature at the data cut-off date of September 10, 2019. Infusion-related reactions (IRR) are an important safety signal associated with margetuximab plus chemotherapy. In SOPHIA, 13% of patients treated with margetuximab plus chemotherapy reported IRRs, of which 1.5% were grade 3. The most commonly reported adverse drug reactions (>10%) with margetuximab in combination with chemotherapy were fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, IRR, palmar-plantar erythrodysesthesia, and extremity pain. Overall, the favorable risk-benefit profile for margetuximab when added to chemotherapy supported its approval for the intended indication.

BACKGROUND Physical therapy and hip arthroscopy are two viable treatment options for patients with nonarthritic hip pain (NAHP); however, patients may experience considerable decisional conflict when making a treatment decision. Interdisciplinary evaluation with a physical therapist and surgeon may better inform the decision-making process and reduce decisional conflict. OBJECTIVE To identify the extent to which an interdisciplinary evaluation between a surgeon, physical therapist, and patient influences treatment plans and decisional conflict of persons with NAHP. DESIGN Randomized controlled trial. SETTING Hip preservation clinic. PARTICIPANTS Adults with primary NAHP. INTERVENTIONS Participants were randomized to receive a standard (surgeon) or interdisciplinary (surgeon+physical therapist) evaluation. Surgeon evaluations included patient interview, strength and range-of-motion examination, palpation, gross motor observation, and special testing. Interdisciplinary evaluations started with the surgeon evaluation, then a physical therapist evaluated movement impairments during sitting, sit-to-stand, standing, single-leg stance, single-leg squat, and walking. All evaluations concluded with treatment planning with the respective provider(s). OUTCOME MEASURES Treatment plan and decisional conflict were collected pre- and postevaluation. Inclusion of physical therapy in participants' postevaluation treatment plans and postevaluation decisional conflict were compared between groups using chi-square tests and Mann-Whitney U tests, respectively. RESULTS Seventy-eight participants (39 in each group) met all eligibility criteria and were included in all analyses. Sixty-six percent of participants who received an interdisciplinary evaluation included physical therapy in their postevaluation treatment plan, compared to 48% of participants who received a standard evaluation (p = .10). Participants who received an interdisciplinary evaluation reported 6.3 points lower decisional conflict regarding their postevaluation plan (100-point scale; p = .04). The interdisciplinary and standard groups reduced decisional conflict on average 24.8 ± 18.9 and 23.6 ± 14.6 points, respectively. CONCLUSIONS Adding a physical therapist to a surgical clinic increased interest in physical therapy treatment, but this increase was not statistically significant. The interdisciplinary group displayed lower postevaluation decisional conflict; however, both groups displayed similar reductions in decisional conflict from pre- to postevaluation. This study also demonstrated the feasibility of an interdisciplinary evaluation in a hip preservation clinic.

Objective Synthesize available evidence that have examined the relationship between physical therapy (PT) and opioid-use. Literature survey Data sources including Google scholar, Embase, PubMed, Cochrane Library, and CINAHL were searched for English articles up to 10-24-2019 using terms ("physical therapy"[Title/Abstract] OR physiotherapy[Title/Abstract] OR rehabilitation[Title/Abstract]) AND (opiate*[Title/Abstract] OR opioid*[Title/Abstract]). Methodology Included studies evaluated a PT intervention and reported an opioid-use outcome. Data were extracted to describe the PT intervention, patient sample, opioid-use measurement, and results of any time or group comparisons. Study quality was evaluated with Joanna Briggs checklists based on study design. Synthesis Thirty studies were included that evaluated PT in at least one of these seven categories: interdisciplinary program (n = 8), modalities (n = 3), treatment (n = 3), utilization (n = 2), content (n = 3), timing (n = 13), and location (n = 2). Mixed results were reported for reduced opioid-use after interdisciplinary care and after PT modalities. Utilizing PT was associated with lower odds (ranging from 0.2-0.8) to use opioid medication for persons with low back pain (LBP) and injured workers; however, guideline-adherent care did not further reduce opioid-use for persons with LBP. Early PT utilization after index visit for spine or joint pain and after orthopaedic surgery was also associated with lower odds to use opioid medications (ranging from 0.27-0.93). Emergency department PT care was not associated with fewer opioid prescriptions than standard emergency department care. PT in a rehabilitation center after total knee replacement was not associated with lower opioid use than inpatient PT. Conclusions The relationship between timing of PT and opioid use was evaluated in 13 of 30 studies for a variety of patient populations. Eight of these 13 studies reported a relationship between early PT and reduced subsequent opioid use, making the largest sample of studies in this scoping review with supporting evidence. There is limited and inconclusive evidence to establish whether the content and/or location of PT interventions improves outcomes due to heterogeneity between studies. This article is protected by copyright. All rights reserved.

Like most events that have taken place since March of last year, the Sundance Film Festival—normally hosted in the cozy ski town of Park City, Utah—was held virtually in 2021. But what it lacked in celebrity sightings and snowy ambiance was more than made up for in the festival's assortment of provocative and timely offerings—from gripping accounts of the COVID-19 pandemic and California's wildfire crisis to mind-bending meditations on the limits of perception and the nature of reality. Read on to see what our reviewers thought of nine of the films that featured strong science and technology themes.

Polytrauma clinical triad (PCT) is the comorbid occurrence of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and pain after trauma. No clinical practice guidelines for postacute care of patients with PCT currently exist; instead, clinical practice guidelines have been published for the three conditions (TBI, PTSD, and pain) as distinct clinical entities. Using multiple, individual practice guidelines for a patient with PCT may lead to unintended prescription of multiple and potentially adversely interacting medications (ie, polypharmacy). Polypharmacy, especially that which includes central nervous system-acting medications, may lead to overdose, suicidality, and chronic symptomatology. Current individual guidelines for each condition of PCT do not address how to coordinate care for the polytraumatic diagnosis. The purpose of this Practice Management piece is to describe the unintended consequences of polypharmacy in patients with PCT and to discuss mitigation approaches including rational prescribing, nonpharmacologic alternatives, and interdisciplinary coordination.

Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core-shell microneedles-which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics-for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.

BACKGROUND Outcomes for operative and nonoperative management of femoroacetabular impingement syndrome (FAIS) are variable. Understanding factors that inform patients' treatment decisions may optimize their outcomes. OBJECTIVE To identify factors that predict which patients with FAIS proceed to surgery within 90 days of their initial evaluation by an orthopedic surgeon. The study explored potential predictors of surgical intervention, including demographic factors, activity level, symptom duration, previous treatment, hip function, pain, presence of labral tear, and patient interest in surgical and physical therapy (PT) treatment. DESIGN Prospective cohort. SETTING Single-site academic medical center. PATIENTS Seventy-seven individuals with FAIS. INTERVENTION After evaluation in a hip preservation clinic, participants reported activity level, symptom duration, treatment history, hip function [Hip Outcome Score Activities of Daily Living(HOS-ADL)], pain severity and location, and treatment interests. These variables were evaluated based on univariate analysis for entry into a multiple binomial logistic regression to identify predictors of surgery within 90 days. Adjusted marginal prevalence ratios and 95% confidence interval estimates (PR [95% CI]) were reported (P ≤ .05). MAIN OUTCOME MEASURE(S) Ninety-day treatment (surgery or not). RESULTS Participants indicated initial interest in surgery (n = 27), PT (n = 22), both (n = 18), or neither (n = 10). Those only interested in PT had lower prevalence of diagnosed labral tear (P

Background Physical therapy and surgery are viable treatment options for nonarthritic hip disease (NAHD). Interdisciplinary collaboration can help patients make informed treatment decisions. Understanding how each provider can contribute is a critical first step in developing collaborative evaluation efforts. Objective The objective of this study was to describe the current evaluation of NAHD by both physical therapists and physicians, and evaluate national use of expert-recommended evaluation guidelines. Design A national survey study distributed in the United States was implemented to accomplish the objective. Methods A survey was distributed to 25,027 potential physical therapist and physician respondents. Respondents detailed their evaluation content for patients with NAHD across the following domains: patient-reported outcomes, patient history, special tests, movement assessment, clinical tests, and imaging. Respondents ranked importance of each domain using a 5-point Likert scale (not important, slightly important, important, very important, or extremely important). Odds ratios (ORs [95% CIs]) were calculated to identify the odds that physical therapists, compared with physicians, would report each evaluation domain as at least very important. Fisher exact tests were performed to identify statistically significant ORs. Results Nine hundred and fourteen participants (3.6%) completed the survey. Physical therapists were more likely to indicate movement assessment (OR: 4.23 [2.99–6.02]) and patient-reported outcomes (OR: 2.56 [1.67–3.99]) as at least very important for determining a diagnosis and plan of care. Physical therapists had lower odds of rating imaging (OR: 0.09 [0.06–0.14]) and special tests (OR: 0.72 [0.53–0.98]) as at least very important compared with physicians. Limitations This survey study did not include many orthopedic surgeons and thus, primarily represents evaluation practices of physical therapists and nonsurgical physicians. Conclusions Physical therapists were more likely to consider movement assessment very important for the evaluation of patients with NAHD, whereas physicians were more likely to consider imaging and special testing very important.

Objective The purpose of this study was to describe movement impairments for persons with femoroacetabular impingement syndrome and their association with function, treatment recommendations, and treatment plans. Methods This report is a secondary, observational analysis of a clinical trial dataset in which participants received an interdisciplinary evaluation from a surgeon and physical therapist. The therapist documented frontal and sagittal plane movement impairments across 6 functional tasks. Associations between number of impairments in each plane and function (33-item International Hip Outcome Tool [iHOT33]) were evaluated using Pearson or Spearman correlations. Joint provider recommendations (physical therapist and surgeon) and participant-reported treatment plans were dichotomized based on the inclusion of physical therapy or not. Logistic regressions were used to examine the effects of (1) iHOT33, total movement impairments, and previous physical therapist treatment on joint provider recommendation and (2) these same variables along with joint provider recommendation on participant treatment plan; prevalence ratios and 95% CIs were reported for significant contributors. Results Thirty-nine participants demonstrated an average iHOT33 of 35.0 (SD = 19.5) and presented with a median 5 frontal and 3 sagittal plane impairments. More frontal plane impairments were associated with worse iHOT33 scores. Twenty-seven participants received a joint provider recommendation that included physical therapy; no significant contributors to these recommendations were identified. Twenty-four of the 27 participants with a physical therapist recommendation included physical therapy in their treatment plan. Two additional participants did not receive a physical therapist recommendation but included physical therapy in their plan. Joint provider recommendation was the only significant contributor to the participant-reported plan (prevalence ratio = 7.06; 95% CI = 3.25–7.97). Conclusion Persons with femoroacetabular impingement syndrome displayed clinically observable movement impairments that were associated with worse function. Joint provider recommendations strongly influenced participants’ treatment plans to pursue physical therapy. Impact Physical therapists contribute new information to surgical examinations regarding movement. Joint recommendations from the physical therapist and the surgeon can influence patients’ decisions to pursue physical therapy.

Objective The purpose of the study was to synthesize studies of movement patterns and their association with hip pain, function/activity, and morphology in individuals with femoroacetabular impingement syndrome (FAIS). Methods PubMed, SPORTDiscus, CINAHL, Embase, and Scopus databases were searched using predefined terms. Two authors independently reviewed abstracts and full texts. Studies were included if they enrolled individuals with FAIS, reported kinematic or kinetic data during movement tasks, and tested the data’s associations with hip pain, function/activity, or morphology. Exclusion criteria were studies that did not evaluate associations between movement patters and pain, function/activity, or hip morphology. Additionally, studies with hip conditions other than FAIS, case reports, conference proceedings, review articles, and non-English studies were excluded. Descriptive consolidation and qualitative synthesis were performed for the included studies. Results Of the 1155 potential studies, 5 studies met all eligibility criteria. Movement patterns were evaluated during walking (n = 4) and squatting (n = 1). Studies reported multiple associations between variables of interest. Statistically significant associations were identified between movement patterns and hip pain (n = 2), function/activity (n = 2), or morphology (n = 3). Significant associations included increased hip flexion moment impulse during walking was associated with worse pain, increased hip flexion moment during walking was associated with worse hip function, decreased hip external rotation during gait and hip internal rotation during squat were associated with larger cam deformity, and increased hip flexion moment impulse during walking was also associated with more severe acetabular cartilage abnormalities. Conclusions Very little current evidence has evaluated the associations between altered movement patterns and hip pain, function/activity, or morphology in individuals with FAIS, and only low-intensity tasks have been tested. These studies found some preliminary associations between altered hip biomechanics and higher hip pain, worse hip function, and specific measures of hip morphology in individuals with FAIS. Impact This review is a first step in gaining a better understanding of movement patterns and their associations with hip pain, function/activity, and morphology, which could ultimately assist with the development of movement retraining interventions and potentially improve rehabilitation outcomes for those with FAIS.

To identify patient- and physical therapist-level predictors for therapeutic alliance at the end of an episode of physical therapy for knee or low back pain (LBP).Secondary analysis of observational cohort.Outpatient physical therapy clinics.Patients receiving physical therapy for knee (n=189) or LBP (n=252) and physical therapists (n=19). Candidate predictor variables included demographics, patient clinical characteristics, and physical therapist attitudes and beliefs (Pain Attitudes and Beliefs Scale for Physical Therapists) and confidence in providing patient-centered care (Self-Efficacy in Patient-Centeredness Questionnaire).Not applicable.Patient-reported therapeutic alliance was measured using the 12-item Work Alliance Inventory-Short Revised (WAI-SR).Final linear mixed models indicated different patient- and physical therapist-level factor contributions in predicting final WAI-SR scores across cohorts with knee and LBP. Female sex was a consistent patient-level predictor for both knee (estimated β=1.57, P.05) and LBP (β=1.42, P.05), with age (β=-0.07, P.01) and baseline function (β=0.06, P.01) contributing to cohorts with knee and LBP, respectively. Physical therapist-level predictors included female sex (β=6.04, P.05), Pain Attitudes and Beliefs Scale for Physiotherapists behavioral (β=0.65, P.01), and Self-Efficacy in Patient-Centeredness Questionnaire (SEPCQ) Exploring Patient Perspective (β=-0.75, P.01) subscale scores for LBP, with SEPCQ Sharing Information and Power subscale scores (β=0.56, P.05) contributing to both cohorts with knee (β=0.56, P.05) and LBP (β=0.74, P.01). Random effects for patients nested within physical therapists were observed for both cohorts.These findings provide preliminary evidence for inconsistent relationships among patient- and physical therapist-level factors and therapeutic alliance across cohorts with knee and LBP.

BACKGROUND Low back pain (LBP) has been associated with worse hip function for persons with femoroacetabular impingement syndrome (FAIS). Reports are limited to surgical populations and based on the presence or absence of LBP, regardless of pain severity. OBJECTIVES To report the prevalence of clinically significant LBP for persons with FAIS; compare demographics, pain, and function between those with and without clinically significant LBP; and evaluate relationships between hip function and both LBP-related disability and LBP severity. We hypothesized that participants with LBP would be older, have higher body mass index (BMI), and report worse groin pain, longer symptom duration, and worse hip function. We hypothesized that worse LBP-related disability and LBP severity would be related to worse hip function. DESIGN Observational cross-sectional study. SETTING Hip preservation clinic. PARTICIPANTS 158 persons with FAIS. INTERVENTIONS n/a MAIN OUTCOME MEASURE(S): Visual analog pain scales (VAS 0-100) were used to categorize participants with (≥30) and without (

Publications reporting discrete choice experiments of healthcare interventions rarely discuss whether patient and public involvement (PPI) activities have been conducted. This paper presents examples from the existing literature and a detailed case study from the National Institute for Health Research-funded PATHWAY programme that comprehensively included PPI activities at multiple stages of preference research. Reflecting on these examples, as well as the wider PPI literature, we describe the different stages at which it is possible to effectively incorporate PPI across preference research, including the design, recruitment and dissemination of projects. Benefits of PPI activities include gaining practical insights from a wider perspective, which can positively impact experiment design as well as survey materials. Further benefits included advice around recruitment and reaching a greater audience with dissemination activities, amongst others. There are challenges associated with PPI activities; examples include time, cost and outlining expectations. Overall, although we acknowledge practical difficulties associated with PPI, this work highlights that it is possible for preference researchers to implement PPI across preference research. Further research systematically comparing methods related to PPI in preference research and their associated impact on the methods and results of studies would strengthen the literature. Electronic supplementary material The online version of this article (10.1007/s40271-020-00439-2) contains supplementary material, which is available to authorized users.

This study assessed how seasonal transitions and coaching influence affect aerobic capacity (AC) and body composition across the annual training cycle (ATC). Eleven division 1 female soccer players were tested after five predesignated time blocks (B1&ndash, B5): post-season 2016 (B1), nine-week transition (B2), spring season (B3), pre-season (B4), and post-season 2017 (B5). Height, weight, and body composition (fat-free mass (FFM)) were measured prior to a standardized 5 min treadmill running and dynamic movement warm up before a maximal AC test. Statistical analysis included a 4 &times, 5 repeated-measures analysis of variance (ANOVA) (dependent variable &times, time) with the Fishers Least Significant Difference (LSD) post-hoc test when relevant, data are presented as mean &plusmn, standard deviation, effect size (ES), and percent change (%). The statistical analysis revealed that the ATC had a significant main effect on AC and FFM (F3,4 2.81, p = 0.001, &eta, 2 = 0.22). There were significant increases in AC across the transition period (B1&ndash, B2) with reduced training volume (∆ + 12.9%, p = 0.001, ES = 0.50) while AC and FFM peaked after the spring season with directed concurrent training paired with adequate rest B1&ndash, B3 (∆ + 16.4%, p &lt, 0.01, ES = 0.81). AC decreased across the pre-season with indirect training (B3&ndash, B4) (∆ &minus, 7.0%, p = 0.02, ES = 0.50) and remained suppressed without change (p &gt, 0.05) across the competitive season (B4&ndash, B5). Rest, concurrent training, and directed training positively affected AC, while indirect training and high training loads with little rest negatively affected AC.

(1) To determine the prevalence of depression in patients undergoing hip arthroscopy for the treatment of femoroacetabular impingement (FAI) syndrome and (2) to determine whether depression has a statistically significant and clinically relevant effect on preoperative and postoperative patient-reported outcome scores.Consecutive subjects undergoing hip arthroscopy for FAI syndrome were retrospectively reviewed. The Beck Depression Inventory-II (BDI-II), Hip Outcome Score (HOS), and 33-item International Hip Outcome Tool (iHOT-33) were administered preoperatively and postoperatively. Clinically relevant differences were defined by the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptom state. Comparisons between preoperative and postoperative scores were completed. The Spearman correlation coefficient (r) was used to determine the degree of correlation between the BDI-II score, HOS, and iHOT-33 score preoperatively and postoperatively.We analyzed 77 patients (72.7% female patients; mean age, 35.2 ± 12.5 years). Depressive symptoms were reported as minimal (75.3%), mild (11.7%), moderate (6.5%), or severe (6.5%). Patients with minimal or mild depression had a superior HOS Activities of Daily Living (Δ17.3 preoperatively [P.001] and Δ37.8 postoperatively [P.001]), HOS Sport-Specific Subscore (Δ12.8 preoperatively [P = .002] and Δ52.1 postoperatively [P.0001]), and iHOT-33 score (Δ15.4 preoperatively [P.0001] and Δ51.3 postoperatively [P.0001]) compared with patients with moderate or severe depression. There was a weak to moderate negative correlation between the BDI-II score and iHOT-33 score (r = -0.4614, P.0001 preoperatively; r = -0.327, P.0001 at 1 year), HOS Activities of Daily Living (r = -0.531, P.0001 preoperatively), and HOS Sport-Specific Subscore (r = -0.379, P.0017 at 1 year).Most patients undergoing hip arthroscopy for FAI have minimal depressive symptoms with the overall prevalence higher than the general population. Patients with minimal or mild depressive symptoms have statistically and clinically better preoperative and postoperative patient-reported outcomes, are more likely to obtain substantial clinical benefit from surgery, and are more likely to reach a patient acceptable symptom state after surgery than patients with moderate to severe depressive symptoms.Level III, case-control study.

Background Suboptimal patient-reported function and movement impairments often persist after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Individuals with FAIS with preoperative cartilage pathology (ie. chondropathy) demonstrate distinct movement patterns and have worse post-operative outcomes. It is unknown whether the presence of chondropathy after surgery negatively affects movement and function. Research question Do sagittal plane gait mechanics differ based on chondropathy severity following arthroscopy for FAIS? Methods A cross-sectional walking gait analysis was performed for 25 participants post-arthroscopy (2.48 ± 1.38y) and 12 healthy controls (HCs). Peak total support moment (TSM) and relative contributions of the hip, knee, and ankle were calculated during loading response. The Hip Osteoarthritis MRI Scoring System was used to categorize the FAIS group into no-mild or moderate-severe chondropathy groups based on 3 T magnetic resonance imaging of their surgical hip. The interactions of group by limb were evaluated for kinetic variables, covaried by gait speed. Results Groups did not differ based on age, BMI and sex distribution (P ≥ 0.14). 13 participants with FAIS presented with moderate-severe chondropathy and 12 presented with no-mild chondropathy. Participants with moderate-severe chondropathy walked significantly slower than both other groups (P = 0.006) and demonstrated lower peak TSM than those with no-mild chondropathy (P = 0.002). Participants with no-mild chondropathy demonstrated lower hip (61.5 %) and greater ankle (17.7 %) contributions to the TSM on the involved limb compared to the moderate-severe group (hip:73.4 %, P = 0.07; ankle:10.5 %, P = 0.007). Significance Slower gait speed alone did not explain the lower TSM strategy in participants with moderate-severe chondropathy. Interestingly, the joint contribution strategy of this group was not different than HCs. Participants with no-mild chondropathy demonstrated a TSM strategy that shifted the demand away from their hip and toward their ankle. Given the small sample size, and large variability in joint strategies, future work needs to examine whether these alterations in gait strategy, with or without advanced chondropathy, impact patient function.

Postoperative gait mechanics in persons with femoroacetabular impingement syndrome (FAIS) remain understudied as a treatment outcome despite observed, yet inconclusive, preoperative gait abnormalities. Females with FAIS demonstrate worse preoperative patient-reported hip function and altered hip mechanics when compared with males; it is unknown whether these sex differences persist postarthroscopy. The purpose of this study was to compare sex-specific gait kinematics between persons at least 1 year postarthroscopy for FAIS and healthy comparisons. General linear models with estimating equations were used to evaluate the effect of (a) limb and sex within each group, and (b) limb and group within each sex for peak sagittal and frontal plane trunk, pelvis, and hip kinematics during stance phase of gait. Analyses were covaried by gait speed. Seventeen females and eight males an average 2.5 years postarthroscopy (1.1-7.2 year) for FAIS were compared with healthy females (n = 7) and males (n = 5). Females in the FAIS group presented with an average of 4.6° more anterior pelvic tilt, and 4.8° less hip extension compared with healthy females (P ≤ .03) and 8.6° less trunk flexion, 4.8° more anterior pelvic tilt, 3.1° more pelvic drop, and 7.5° more hip flexion than males with FAIS (P ≤ .03). Males in the FAIS group presented with 2.9° less pelvic drop, and 3.2° less hip adduction than healthy males. Preoperative gait mechanics were not collected and thus changes in mechanics could not be evaluated. This study is significant to clinicians who treat patients postarthroscopy to consider sex-specific gait impairments.

BACKGROUND: Non-arthritic hip disease (NAHD) is a clinical condition often accompanied by painful movement. Current literature is lacking regarding how movement abnormalities are evaluated and treated in this population, which may be key to identifying which patients may respond to non-operative versus operative treatment. Combining the expertise of a hip arthroscopist and physical therapist may better inform treatment decisions for persons with NAHD. The primary objective of this study is to identify the extent to which an interdisciplinary evaluation between a physical therapist and surgeon influences treatment decisions of persons presenting to a hip preservation clinic. RATIONALE FOR STUDY DESIGN: A prospective, randomized controlled trial provides the ability to identify cause and effect of this new evaluation type. METHODS: Ninety-six adults with unilateral, NAHD presenting to a hip preservation clinic for initial evaluation will be randomized to receive either a standard evaluation with a surgeon or an interdisciplinary evaluation by a physical therapist and surgeon. Regardless of group, the surgeon conducts a standard-care examination. For participants in the interdisciplinary group, the physical therapist conducts an assessment of 6 postures and movements to identify asymmetrical, abnormal, or painful strategies. Treatment selection(s) and decisional conflict will be compared between groups after the evaluations. DISCUSSION: Persons with NAHD may experience considerable decisional conflict because of prolonged duration of symptoms and minimal evidence to compare operative and non-operative treatment for this population. The findings of this study have the potential to improve patient experience and produce more informed and supported treatment decisions for persons considering surgical treatment for NAHD.

Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core-shell microneedles-which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics-for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.

TIR domain containing proteins are important immune associated proteins shared among Toll-like and interleukin-1/18 receptor family members. In a recent discovery select bacterial, plant and human TIR proteins exhibit enzymatic activity in binding and processing nicotinamide adenine dinucleotide (NAD+). Based on their abilities to facilitate signaling across biology, we hypothesize that TIR proteins represent unique therapeutic targets for modulating infection, inflammation and disease. Our previous structural studies of bacterial-host TIR proteins B. melitensis (TcpB) and uropathogenic E. coli CFT073 (TcpC) with human host TIRAP and MyD88 characterized peptides that negatively regulate signaling and infection. From these studies we identified interactions that are at or near reported biological TIR protein interfaces. In particular, we identified a functionally important motif found conserved on the C helix of most bacterial, human host and NAD+ consuming TIR proteins. As proof of concept for select targeting of TIR proteins and this region in particular we have used the TLR4 antagonist, TAK-242, which selectively binds within this motif. Treatment with TAK-242 or TLR4-C747S blocks LPS signaling. Additionally, TAK-242 protected mice from lethal influenza challenge similar to an extracellular TLR4 antagonist, Eritoran. Bioinformatic analysis of the region targeted by TAK242 show that it is located within the WxxxE structural motif identified to be important for protecting against microtubule destabilization and includes a catalytically essential glutamic acid (E) residue conserved among nearly all NAD+ consuming TIR proteins. These studies provide a framework for future studies targeting TIR protein function.

A recurring single amino acid somatic mutation associated with human diffuse large B cell lymphomas (DLBCLs), correlates with tumor cell proliferation and survival involving spontaneous and sustained activation of MyD88-dependent NF-κB and Janus Kinase (JAK) signaling pathways. MyD88 acts as a central signaling adapter for mediating innate and cytokine driven inflammation for the Interleukin-1 (IL-1R) and Toll-like receptors (TLRs). Computer aided molecular modeling of MyD88 and in silico screening have identified and functionally characterized MyD88 specific small molecule compounds shown to protect against Staphylococcal enterotoxin B (SEB) induced death in animal models. We hypothesize that MyD88 specific small molecule compounds may also be useful in treating DLBCLs bearing the oncogenic mutation MYD88L265P. Using in vitro and in vivo studies we evaluate MyD88 specific small molecule compounds for the ability to inhibit tumor cell proliferation and signaling in human patient cancer cells OCI Ly3 bearing the oncogenic mutation MYD88 L265P and OCI Ly19 DLBCLs. Previously we identified differences in the ability of MyD88 small molecule compounds to inhibit cell proliferation in activated human B cell lymphoma cells bearing the MyD88 L265P mutation. We now correlate these differences with a reduction of MyD88 interaction with IRAK in small molecule treated OCI-Ly3 cells bearing the MYD88 L265P mutation in comparison to OCI-Ly19 (wt-MyD88) and treated controls, as measured by CoIP. We continue to characterize MyD88 specific small molecule compounds that target MyD88 dimerization for their ability to reduce MyD88 containing signaling complexes in DLBCLs bearing MYD88 L265P mutation.

Background Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study within which the Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. PEARL incorporated qualitative research to seek the views of young people about data linkage, including their opinions about appropriate safeguards and research governance. In this paper we focus on views expressed about the purpose and composition of research ethics committees. Methods Digitally recorded interviews were conducted with 48 participants aged 17–19 years. Participants were asked about whether medical research should be monitored and controlled, their knowledge of research ethics committees, who should sit on these committees and what their role should be. Interview recordings were fully transcribed and anonymised. Thematic analysis was undertaken, assisted by the Framework approach to data management. Results The majority of interviewees had little or no specific knowledge of ethics committees. Once given basic information about research ethics committees, only three respondents suggested there was no need for such bodies to scrutinise research. The key tasks of ethics committees were identified as monitoring the research process and protecting research participants. The difficulty of balancing the potential to inhibit research against the need to protect research participants was acknowledged. The importance of relevant research and professional expertise was identified but it was also considered important to represent wider public opinion, and to counter the bias potentially associated with self-selection possibly through a selection process similar to ‘jury duty’. Conclusions There is a need for more education and public awareness about the role and composition of research ethics committees. Despite an initial lack of knowledge, interviewees were able to contribute their ideas and balance the rights of individuals with the wider benefits from research. The suggestion that public opinion should be represented through random selection similar to jury duty may be worth pursuing in the light of the need to ensure diversity of opinion and establish trust amongst the general public about the use of ‘big data’ for the wider public good.

This study examined the impact of an afterschool program on resilience in youth at an elementary school in Central NY. The goals of the program were to: (a) increase resiliency among participants, and (b) reduce the occurrence of aggressive behaviors (i.e., bullying) in 5th and 6th graders. Of the 79 students who completed the survey, 19 participants were able to be matched with pre- and posttests. In the study, 13 as participants in the afterschool program, and six as non-participants. Results of paired samples t-tests indicated that those who participated in the afterschool program showed a significant increase (p= 0.05) in resiliency scores. The program also had a positive impact on decreasing discipline-related referrals.

The purpose of this study was to adapt and experimentally test the effectiveness of a research-based, employment-focused group counseling intervention (OPTIONS). OPTIONS was designed to increase male inmates’ exploration and identification of employment interests and options, identification and development of employment-search skills, and knowledge of vocational options, goal planning, and identification and use of contextual supports. A randomized block design and measurements at pretest, posttest, and 1-month follow-up were used to examine the effects of OPTIONS. Participants included 77 ( n = 38 treatment, n = 39 control) adult male inmates. Results indicated that OPTIONS participants had higher career search self-efficacy, problem solving, and hopefulness scores at posttest and follow-up than did treatment-as-usual control group participants.