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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.

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.

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.

(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 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.

Background: Femoroacetabular impingement (FAI) is a significant cause of disability in young adults. Hip arthroscopic surgery restores bony congruence and improves function in the majority of patients, but recent evidence indicates that women may experience worse pre- and postoperative function than men. Purpose/Hypothesis: The purpose of this study was to identify whether self-reported hip function differed between men and women with symptomatic FAI. The hypothesis was that mean self-reported hip function scores would improve after arthroscopic surgery but that women would report poorer function than men both before and up to 2 years after arthroscopic surgery. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 229 patients (68.4% women; mean [±SD] age, 31.6 ± 10.8 years; mean [±SD] body mass index, 26.8 ± 11.9 kg/m2) underwent hip arthroscopic surgery for unilateral symptomatic FAI. All eligible and consenting patients with radiologically and clinically confirmed FAI completed the International Hip Outcome Tool (iHOT-33) and the Hip Outcome Score activities of daily living subscale (HOS-ADL) before hip arthroscopic surgery and at 3, 6, 12, and 24 months after arthroscopic surgery. A linear mixed model for repeated measures was used to test for differences in self-reported hip function between men and women over the study period ( P ≤ .05). Results: There were no significant time × sex interactions for either the HOS-ADL ( P = .12) or iHOT-33 ( P = .64), but both measures showed significant improvements between the preoperative time point and each of the 4 follow-up points ( P < .0001); however, self-reported hip function did not improve between 6 and 24 months after arthroscopic surgery ( P ≥ .11). Post hoc independent t tests indicated that women reported poorer hip function than did men before surgery ( P ≤ .003) both on the HOS-ADL (mean ± standard error of the mean [SEM], 67.4 ± 1.9 [men] vs 60.5 ± 1.3 [women]) and iHOT-33 (mean ± SEM, 38.0 ± 1.9 [men] vs 30.9 ± 1.3 [women]); scores were not different between sexes at any other time point. Conclusion: These findings indicate improvements in self-reported hip function in patients with FAI, regardless of sex, until 6 months after hip arthroscopic surgery. Although women reported poorer preoperative function than did men, the differences were not significant 2 years after surgery.

Background Electronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study. 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. Qualitative research was incorporated in the PEARL study to examine participants’ views about data linkage and inform approaches to information sharing. This paper focusses on issues of consent. Methods Digitally recorded interviews were conducted with 55 participants aged 17–19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach. Results Participant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with ‘opt-in’ consent through which participants are ‘asked’ if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented with different scenarios, and were sometimes inconsistent. Conclusions Findings from this study question the validity of ‘informed consent’ as a cornerstone of good governance, and the extent to which potential research participants understand different types of consent and what they are consenting, or not consenting, to. Pragmatic, imaginative and flexible approaches are needed if research using data linkage is to successfully realise its potential for public good without undermining public trust in the research process.

The purpose of this study was to ascertain whether a measurable difference existed in normative scores for the American Shoulder and Elbow Surgeons (ASES) questionnaire between subjects who had an active workers' compensation claim (WC) with no known shoulder injury and subjects without a compensation claim (non-WC). Subjects with non-shoulder-related orthopaedic injuries were recruited from a suburban orthopaedic sports medicine clinic and an urban occupational medicine clinic. They were asked to complete a composite questionnaire that consisted of demographic information and the ASES questionnaire. There were no significant differences in the ASES scores between subject groups. There were significant differences between subject groups with regard to work hours (P = .0001), work demands (P = .0001), and tobacco use (P = .0001). Subject group was also significantly associated with education level (P = .0001), marital status (P = .0001), work demands (P = .0001), gender (P = .0001), and sports participation (P = .0314). The ASES score was significantly affected by marital status (P = .0476), sports participation (P = .0008), and age (P = .0129).

Background Attrition is an important problem in cohort studies. Tracing cohort members who have moved or otherwise lost contact with the study is vital. There is some debate about the acceptability and relative effectiveness of opt-in versus opt-out methods of contacting cohort members to re-engage them in this context. We conducted a randomised controlled trial to compare the two approaches in terms of effectiveness (tracing to confirm address and consenting to continue in the study), cost-effectiveness and acceptability. Methods Participants in this trial were individuals (young people and mothers) recruited to the Avon Longitudinal Study of Parents and Children (ALSPAC), who had not engaged with the study in the previous 5 years and for whom mail had been returned from their last known address. The sampling frame was restricted to those for whom database searching led to a potential new address being found in the Bristol area. 300 participants were randomly selected and assigned using stratified randomisation to the opt-in or opt-out arm. A tailored letter was sent to the potential new address, either asking participants to opt in to a home visit, or giving them the option to opt out of a home visit. Fieldworkers from Ipsos MORI conducted home visits to confirm address details. Results The proportion who were traced was higher in the opt-out arm (77/150 = 51 %) than the opt-in arm (6/150 = 4 %), as was the proportion who consented to continue in ALSPAC (46/150 = 31 % v 4/150 = 3 %). The mean cost per participant was £8.14 in the opt-in arm and £71.93 in the opt-out arm. There was no evidence of a difference in acceptability between the opt-in and opt-out approaches. Conclusion Since the opt-in approach yielded very low response rates, and there were no differences in terms of acceptability, we conclude that the opt-out approach is the most effective method of tracing disengaged study members. The gains made in contacting participants must be weighed against the increase in cost using this methodology. Electronic supplementary material The online version of this article (doi:10.1186/s12874-015-0041-y) contains supplementary material, which is available to authorized users.

Disability is as much a factor in interactional dynamics as ethnicity, age, gender or sexuality, and therefore its impact on the processes around qualitative research warrants much more systematic attention. Disabled researchers are not confined to disability studies research, although most accounts of the impact of disability on the research process have, thus far, been undertaken within this field. This paper moves beyond this narrow focus to consider the impact of disabled identities and the embodied experiences of impairment on studies involving, primarily, non-disabled people. By reflecting on our experiences as visibly disabled researchers, we highlight some of the practical, ethical and conceptual dilemmas we encountered. Impairments may assist rapport building with participants, but also introduce complex dilemmas concerning whether, when and how to disclose them, and the consequences of doing so. We highlight the centrality of the visibility of the disabled body in mediating these dilemmas, and its part in constraining our responses to them. While we value our commitment to positive readings of disability, we demonstrate that disabled researchers nevertheless undertake research in contexts where disability is assigned meanings disabled people may not share. We argue that all researchers should attend to their own ‘body signifiers’ (whether in relation to ethnicity, wealth, gender, age etc.) and embodied experiences of research processes, as these are integral to research outcomes, the ethics of research, and are a means by which to address power differentials between researcher and participant. This paper addresses a gap in the literature, using our experiences of research to highlight the negotiations and dilemmas faced by visibly disabled researchers. Negotiations of identity prompted by the disabled body in the research process require consideration and should not be ignored.\ud \ud