A single-day polychemotherapy regimen with proteasome inhibitor combinations for relapsed/refractory myeloma in the era of novel therapies.

PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37-80), with a median of four (1-8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5-6.7) and 7.4 months (95% CI 6.4-10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6-13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4-39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.

Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Is it time to develop specific return to running criteria for ACL rehabilitation? An international survey of physiotherapists criteria for return to running following ACL injury.

OBJECTIVE: To determine return to running criteria currently used by physiotherapists following anterior cruciate ligament (ACL) injury. DESIGN: Self-reported online international survey. METHODS: An online survey of physiotherapists across Australia, the Netherlands and France. RESULTS: A total of 476 respondants participated in the survey across Australia (n = 153), the Netherlands (n = 162), and France (n = 161). For return to running criteria following a non-operative approach, the majority of respondents chose swelling (40.55%, n = 193/476), pain (38.24%, n = 182/476), knee extensor strength (34.34%, n = 163/476), single leg squat (31.93%, n = 152/476) and knee flexor strength (29.83%, n = 142/476). After ACL reconstruction, the highest responses were also swelling (41.18%, n = 196/476), pain (37.18%, n = 177/476), knee extensor strength (37.18%, n = 177/476) and single leg squat (33.19%, n = 158/476). From the identified themes the most common cutoff variables were pain between 0 and 3/10, swelling < grade 1+ and limb symmetry on strength and hop tests >70 %. CONCLUSION: Physiotherapists in Australia, France, and the Netherlands use many different return to running criteria and most of them use more than one criterion. Despite this, there was little consensus on the cut-off physiotherapists use to apply these criteria.

Neuromuscular Control and Resistance Training for People With Chronic Low Back Pain: A Randomized Controlled Trial.

OBJECTIVE: To determine if adding lumbar neuromuscular control retraining exercises to a 12-week program of strengthening exercises had greater effect for improving disability than 12 weeks of strengthening exercises alone in people with chronic low back pain (LBP). DESIGN: Single-center, participant- and assessor-blinded, comparative effectiveness randomized controlled trial. METHODS: Sixty-nine participants (31 females; 29 males; mean age: 46.5 years) with nonspecific chronic LBP were recruited for a 12-week program involving lumbar extension neuromuscular retraining in addition to resistance exercises (intervention) or 12 weeks of resistance exercises alone (control). The primary outcome measure was the Oswestry Disability Index. Secondary outcome measures included the Numeric Rating Scale, Tampa Scale for Kinesiophobia, Pain Self-Efficacy Questionnaire, and the International Physical Activity Questionnaire. Outcomes were measured at baseline, 6 weeks, and 12 weeks. RESULTS: Forty-three participants (22 control, 21 intervention) completed all outcome measures at 6 and 12 weeks. Fourteen participants were lost to follow-up, and 12 participants discontinued due to COVID-19 restrictions. Both groups demonstrated clinically important changes in disability, pain intensity, and kinesiophobia. The difference between groups with respect to disability was imprecise and not clinically meaningful (mean difference, -4.4; 95% CI: -10.2, 1.4) at 12 weeks. Differences in secondary outcomes at 6 or 12 weeks were also small with wide confidence intervals. CONCLUSIONS: Adding lumbar neuromuscular control retraining to a series of resistance exercises offered no additional benefit over resistance exercises alone over a 12-week period. J Orthop Sports Phys Ther 2024;54(5):1-10. Epub 18 March 2024. doi:10.2519/jospt.2024.12349.

Regression-Based Machine Learning for Predicting Lifting Movement Pattern Change in People with Low Back Pain.

Machine learning (ML) algorithms are crucial within the realm of healthcare applications. However, a comprehensive assessment of the effectiveness of regression algorithms in predicting alterations in lifting movement patterns has not been conducted. This research represents a pilot investigation using regression-based machine learning techniques to forecast alterations in trunk, hip, and knee movements subsequent to a 12-week strength training for people who have low back pain (LBP). The system uses a feature extraction algorithm to calculate the range of motion in the sagittal plane for the knee, trunk, and hip and 12 different regression machine learning algorithms. The results show that Ensemble Tree with LSBoost demonstrated the utmost accuracy in prognosticating trunk movement. Meanwhile, the Ensemble Tree approach, specifically LSBoost, exhibited the highest predictive precision for hip movement. The Gaussian regression with the kernel chosen as exponential returned the highest prediction accuracy for knee movement. These regression models hold the potential to significantly enhance the precision of visualisation of the treatment output for individuals afflicted with LBP.

Machine Learning Derived Lifting Technique in People without Low Back Pain.

This paper presents a method for determining the number of lifting techniques used by healthy individuals through the analysis of kinematic data collected from 115 participants utilizing an motion capture system. The technique utilizes a combination of feature extraction and Ward's method to analyse the range of motion in the sagittal plane of the knee, hip, and trunk. The findings identified five unique lifting techniques in people without low back pain. The multivariate analysis of variance statistical analysis reveals a significant difference in the range of motion in the trunk, hip and knee between each cluster for healthy people (F (12, 646) = 125.720, p < 0.0001).Clinical Relevance- This information can assist healthcare professionals in choosing effective treatments and interventions for those with occupational lower back pain by focusing rehabilitation on specific body parts associated with problematic lifting techniques, such as the trunk, hip, or knee, which may lead to improved pain and disability outcomes, exemplifying precision medicine.

Impaired Lumbar Extensor Force Control Is Associated with Increased Lifting Knee Velocity in People with Chronic Low-Back Pain.

The ability of the lumbar extensor muscles to accurately control static and dynamic forces is important during daily activities such as lifting. Lumbar extensor force control is impaired in low-back pain patients and may therefore explain the variances in lifting kinematics. Thirty-three chronic low-back pain participants were instructed to lift weight using a self-selected technique. Participants also performed an isometric lumbar extension task where they increased and decreased their lumbar extensor force output to match a variable target force within 20-50% lumbar extensor maximal voluntary contraction. Lifting trunk and lower limb range of motion and angular velocity variables derived from phase plane analysis in all planes were calculated. Lumbar extensor force control was analyzed by calculating the Root-Mean-Square Error (RMSE) between the participants' force and the target force during the increasing (RMSEA), decreasing (RMSED) force portions and for the overall force error (RMSET) of the test. The relationship between lifting kinematics and RMSE variables was analyzed using multiple linear regression. Knee angular velocity in the sagittal and coronal planes were positively associated with RMSEA (R2 = 0.10, ß = 0.35, p = 0.046 and R2 = 0.21, ß = 0.48, p = 0.004, respectively). Impaired lumbar extensor force control is associated with increased multiplanar knee movement velocity during lifting. The study findings suggest a potential relationship between lumbar and lower limb neuromuscular function in people with chronic low-back pain.

Is quadriceps strength associated with patellofemoral joint loading after anterior cruciate ligament reconstruction?

OBJECTIVE: To test whether quadriceps strength is associated with measures of patellofemoral (PF) joint loading during running and hopping in people after an anterior cruciate ligament reconstruction (ACLR). DESIGN: Cross-sectional study. SETTING: Biomechanics laboratory. PARTICIPANTS: Sixty-five participants (24 women; 41 men) 1-2 years post-ACLR. MAIN OUTCOME MEASURES: Peak isometric quadriceps strength for the surgical limb was measured using a dynamometer. Motion analysis and ground reaction force data were combined with musculoskeletal modelling to measure PF joint loading variables for the reconstructed knee (peak knee flexion angle; peak/impulse of the PF joint contact force; time to peak PF joint contact force) during the stance phase of running and during the landing phase of a standardised forward hop. Linear regression analysis (adjusting for age and sex) assessed the association between quadriceps strength and PF joint loading variables. RESULTS: Two significant, albeit modest, associations were revealed. Quadriceps strength was associated with the time to peak PF joint contact force during running (ß = -0.001; 95%CI -0.002 to -0.000; R2 = 0.179) and the impulse of the PF joint contact force during hopping (ß = 0.014; 95%CI 0.003 to 0.024; R2 = 0.159). CONCLUSIONS: A strong link between quadriceps strength and PF joint loading was not evident in people 1-2 years post-ACLR.

Health-seeking behaviors, management practices, and return to play decisions after an ankle sprain in netball: An international cross-sectional survey of 1592 non-elite netballers.

OBJECTIVES: Evaluate if non-elite netballers sought health care, treatments received, and return-to-play decisions after an ankle sprain, including intercountry differences. DESIGN: Cross-sectional survey. METHODS: Non-elite netballers aged >14 years were recruited from Australia, United Kingdom, and New Zealand. Participants completed an online survey regarding their last ankle sprain and were queried regarding health care sought, health professionals consulted, treatments received, time missed, and return-to-play clearance. Data were described using number (proportion) for the overall cohort and countries. Between-country differences in health care use were compared using chi-square tests. Descriptive statistics were presented for management practices. RESULTS: We received 1592 responses from Australian (n = 846), United Kingdom (n = 454), and New Zealand (n = 292) netballers. Three in five (n = 951, 60 %) sought health care. Of those, most consulted a physiotherapist (n = 728, 76 %), received strengthening exercises (n = 771, 81 %), balance exercises (N = 665, 70 %) and taping (n = 636, 67 %). Few received return-to-play clearance (n = 362, 23 %). Comparing countries, fewer United Kingdom netballers sought health care than Australian and New Zealand netballers (Australia: 60 % vs United Kingdom: 53 % vs New Zealand: 68 %, p < 0.001), consulted a physiotherapist (Australia: 79 %, United Kingdom: 63 %, New Zealand: 87 %), received strengthening (Australia: 84 %, United Kingdom: 73 %, New Zealand: 84 %) or balance exercises (Australia: 71 %, United Kingdom: 60 %, New Zealand: 80 %) or taping (Australia: 74 %, United Kingdom: 39 %, New Zealand: 82 %). More Australian netballers returned to play within 1-7 days (Australia: 25 %, United Kingdom: 15 %, New Zealand: 21 %) and fewer United Kingdom netballers received return-to-play clearance (Australia: 28 %, United Kingdom: 10 %, New Zealand: 28 %). CONCLUSIONS: Health-seeking behaviours are adopted by some, but not all netballers after an ankle sprain. For those who sought care, most consulted a physiotherapist and were prescribed exercise-based interventions and external ankle support, but few received return-to-play clearance. Comparing countries, United Kingdom netballers had lower health-seeking behaviours and received less best-practice management than Australian and New Zealand netballers.

Limiting the Use of Electromyography and Ground Reaction Force Data Changes the Magnitude and Ranking of Modelled Anterior Cruciate Ligament Forces.

Neuromusculoskeletal models often require three-dimensional (3D) body motions, ground reaction forces (GRF), and electromyography (EMG) as input data. Acquiring these data in real-world settings is challenging, with barriers such as the cost of instruments, setup time, and operator skills to correctly acquire and interpret data. This study investigated the consequences of limiting EMG and GRF data on modelled anterior cruciate ligament (ACL) forces during a drop-land-jump task in late-/post-pubertal females. We compared ACL forces generated by a reference model (i.e., EMG-informed neural mode combined with 3D GRF) to those generated by an EMG-informed with only vertical GRF, static optimisation with 3D GRF, and static optimisation with only vertical GRF. Results indicated ACL force magnitude during landing (when ACL injury typically occurs) was significantly overestimated if only vertical GRF were used for either EMG-informed or static optimisation neural modes. If 3D GRF were used in combination with static optimisation, ACL force was marginally overestimated compared to the reference model. None of the alternative models maintained rank order of ACL loading magnitudes generated by the reference model. Finally, we observed substantial variability across the study sample in response to limiting EMG and GRF data, indicating need for methods incorporating subject-specific measures of muscle activation patterns and external loading when modelling ACL loading during dynamic motor tasks.

Do biomechanical foot-based interventions reduce patellofemoral joint loads in adults with and without patellofemoral pain or osteoarthritis? A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of biomechanical foot-based interventions (eg, footwear, insoles, taping and bracing on the foot) on patellofemoral loads during walking, running or walking and running combined in adults with and without patellofemoral pain or osteoarthritis. DESIGN: Systematic review with meta-analysis. DATA SOURCES: MEDLINE, CINAHL, SPORTdiscus, Embase and CENTRAL. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: English-language studies that assessed effects of biomechanical foot-based interventions on peak patellofemoral joint loads, quantified by patellofemoral joint pressure, reaction force or knee flexion moment during gait, in people with or without patellofemoral pain or osteoarthritis. RESULTS: We identified 22 footwear and 11 insole studies (participant n=578). Pooled analyses indicated low-certainty evidence that minimalist footwear leads to a small reduction in peak patellofemoral joint loads compared with conventional footwear during running only (standardised mean difference (SMD) (95% CI) = -0.40 (-0.68 to -0.11)). Low-certainty evidence indicated that medial support insoles do not alter patellofemoral joint loads during walking (SMD (95% CI) = -0.08 (-0.42 to 0.27)) or running (SMD (95% CI) = 0.11 (-0.17 to 0.39)). Very low-certainty evidence indicated rocker-soled shoes have no effect on patellofemoral joint loads during walking and running combined (SMD (95% CI) = 0.37) (-0.06 to 0.79)). CONCLUSION: Minimalist footwear may reduce peak patellofemoral joint loads slightly compared with conventional footwear during running only. Medial support insoles may not alter patellofemoral joint loads during walking or running and the evidence is very uncertain about the effect of rocker-soled shoes during walking and running combined. Clinicians aiming to reduce patellofemoral joint loads during running in people with patellofemoral pain or osteoarthritis may consider minimalist footwear.

Patellofemoral joint loading and early osteoarthritis after ACL reconstruction.

Patellofemoral joint (PFJ) osteoarthritis is common following anterior cruciate ligament reconstruction (ACLR) and may be linked with altered joint loading. However, little is known about the cross-sectional and longitudinal relationship between PFJ loading and osteoarthritis post-ACLR. This study tested if altered PFJ loading is associated with prevalent and worsening early PFJ osteoarthritis post-ACLR. Forty-six participants (mean ± 1 SD age 26 ± 5 years) approximately 1-year post-ACLR underwent magnetic resonance imaging (MRI) and biomechanical assessment of their reconstructed knee. Trunk and lower-limb kinematics plus ground reaction forces were recorded during the landing phase of a standardized forward hop. These data were input into a musculoskeletal model to calculate the PFJ contact force. Follow-up MRI was completed on 32 participants at 5-years post-ACLR. Generalized linear models (Poisson regression) assessed the relationship between PFJ loading and prevalent early PFJ osteoarthritis (i.e., presence of a PFJ cartilage lesion at 1-year post-ACLR) and worsening PFJ osteoarthritis (i.e., incident/progressive PFJ cartilage lesion between 1- and 5-years post-ACLR). A lower peak PFJ contact force was associated with prevalent early PFJ osteoarthritis at 1-year post-ACLR (n = 14 [30.4%]; prevalence ratio: 1.37; 95% confidence interval [CI]: 1.02-1.85) and a higher risk of worsening PFJ osteoarthritis between 1- and 5-years post-ACLR (n = 9 [28.1%]; risk ratio: 1.55, 95% CI: 1.13-2.11). Young adults post-ACLR who exhibited lower PFJ loading during hopping were more likely to have early PFJ osteoarthritis at 1-year and worsening PFJ osteoarthritis between 1- and 5-years. Clinical interventions aimed at mitigating osteoarthritis progression may be beneficial for those with signs of lower PFJ loading post-ACLR.

Phase I Study of Safety and Pharmacokinetics of RO7297089, an Anti-BCMA/CD16a Bispecific Antibody, in Patients with Relapsed, Refractory Multiple Myeloma.

INTRODUCTION: This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody. METHODS: RO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model. RESULTS: Overall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%). CONCLUSIONS: RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www. CLINICALTRIALS: gov/ct2/show/NCT04434469 .

External Ankle Support and Ankle Biomechanics in Chronic Ankle Instability: Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically review the literature to determine whether external ankle supports influence ankle biomechanics in participants with chronic ankle instability (CAI) during sport-related tasks. DATA SOURCES: A literature search of MEDLINE, SPORTDiscus, and CINAHL databases was conducted in November 2021. STUDY SELECTION: Included studies were randomized crossover or parallel-group controlled trials in which researchers assessed ankle biomechanics during landing, running, or change of direction in participants with CAI using external ankle supports compared with no support. DATA EXTRACTION: Two authors independently identified studies, extracted data, and assessed risk of bias (Cochrane risk-of-bias tool version 2) and quality of evidence (Grading of Recommendations Assessment, Development and Evaluation). Random-effects meta-analysis was used to compare between-groups mean differences with 95% CIs. Grading of Recommendations Assessment, Development and Evaluation recommendations were used to determine the certainty of findings. DATA SYNTHESIS: A total of 13 studies of low to moderate risk of bias were included. During landing, very low-grade evidence indicated external ankle supports reduce frontal-plane excursion (mean difference [95% CI] = -1.83° [-2.97°, -0.69°], P = .002), plantar-flexion angle at initial contact (-3.86° [-6.18°, -1.54°], P = .001), and sagittal-plane excursion (-3.45° [-5.00°, -1.90°], P < .001) but not inversion angle at initial contact (-1.00° [-3.59°, 1.59°], P = .45). During running, very low- to low-grade evidence indicated external ankle supports reduce sagittal-plane excursion (-5.21° [-8.59°, -1.83°], P = .003) but not inversion angle at initial contact (0.32° [-2.11°, 1.47°], P = .73), frontal-plane excursion (-1.31° [-3.24°, 0.63°], P = .19), or plantar-flexion angle at initial contact (-0.12° [-3.54°, 3.29°], P = .94). Studies investigating changes of direction were insufficient. CONCLUSIONS: Very low-grade evidence indicated external ankle supports reduce frontal-plane excursion but not inversion angle at initial contact in participants with CAI during landing. Limiting frontal-plane excursion may reduce ankle-sprain risk. Frontal-plane ankle kinematics were not influenced by external ankle supports during running. Sagittal-plane reductions were observed with external ankle supports during landing and running with low to very low certainty, but their influence on ankle-sprain risk is undetermined.

The effect of biomechanical foot-based interventions on patellofemoral joint loads during gait in adults with and without patellofemoral pain or osteoarthritis: a systematic review protocol.

BACKGROUND: Patellofemoral pain is highly prevalent across the lifespan, and a significant proportion of people report unfavourable outcomes years after diagnosis. Previous research has implicated patellofemoral joint loading during gait in patellofemoral pain and its sequelae, patellofemoral osteoarthritis. Biomechanical foot-based interventions (e.g., footwear, insoles, orthotics, taping or bracing) can alter patellofemoral joint loads by reducing motions at the foot that increase compression between the patella and underlying femur via coupling mechanisms, making them a promising treatment option. This systematic review will summarise the evidence about the effect of biomechanical foot-based interventions on patellofemoral joint loads during gait in adults with and without patellofemoral pain and osteoarthritis. METHODS: MEDLINE (Ovid), the Cumulative Index to Nursing and Allied Health Literature CINAHL, The Cochrane Central Register of Controlled Trials (CENTRAL), SPORTdiscus (EBSCO) and Embase (Ovid) will be searched. Our search strategy will include terms related to 'patellofemoral joint', 'loads' and 'biomechanical foot-based interventions'. We will include studies published in the English language that assess the effect of biomechanical foot-based interventions on patellofemoral joint loads, quantified by patellofemoral joint pressure, patellofemoral joint reaction force and/or knee flexion moment. Two reviewers will independently screen titles and abstracts, complete full-text reviews, and extract data from included studies. Two reviewers will assess study quality using the Revised Cochrane Risk of Bias (RoB 2) tool or the Cochrane Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool. We will provide a synthesis of the included studies' characteristics and results. If three or more studies are sufficiently similar in population and intervention, we will pool the data to conduct a meta-analysis and report findings as standardised mean differences with 95% confidence intervals. If a meta-analysis cannot be performed, we will conduct a narrative synthesis of the results and produce forest plots for individual studies. DISCUSSION: This protocol outlines the methods of a systematic review that will determine the effect of biomechanical foot-based interventions on patellofemoral joint loads. Our findings will inform clinical practice by identifying biomechanical foot-based interventions that reduce or increase patellofemoral joint loads, which may aid the treatment of adults with patellofemoral pain and osteoarthritis. TRIAL REGISTRATION: Registered with PROSPERO on the 4th of May 2022 (CRD42022315207).

Ballistic resistance training has a similar or better effect on mobility than non-ballistic exercise rehabilitation in people with a traumatic brain injury: a randomised trial.

QUESTIONS: In people recovering from traumatic brain injury, is a 3-month ballistic resistance training program targeting three lower limb muscle groups more effective than non-ballistic exercise rehabilitation for improving mobility, strength and balance? Does improved mobility translate to better health-related quality of life? DESIGN: A prospective, multicentre, randomised trial with concealed allocation, intention-to-treat analysis and blinded measurement. PARTICIPANTS: A total of 144 people with a neurological movement disorder affecting mobility as a result of traumatic brain injury. INTERVENTION: For 3 months, the experimental group had three 60-minute sessions of non-ballistic exercise rehabilitation per week replaced by ballistic resistance training. The control group had non-ballistic exercise rehabilitation of equivalent time. The non-ballistic exercise rehabilitation consisted of balance exercises, lower limb stretching, conventional strengthening exercises, cardiovascular fitness training and gait training. OUTCOME MEASURES: The primary outcome was mobility measured using the High-Level Mobility Assessment Tool (HiMAT). Secondary outcomes were walking speed, strength, balance and quality of life. They were measured at baseline (0 months), after completion of the 3-month intervention (3 months) and 3 months after cessation of intervention (6 months). RESULTS: After 3 months of ballistic resistance training, the experimental group scored 3 points (95% CI 0 to 6) higher on the 54-point HiMAT than the control group and remained 3 points (95% CI -1 to 6) higher at 6 months. Although there was a transient decrement in balance at 3 months in the experimental group, the interventions had similar effects on all secondary outcomes by 6 months. Participants with a baseline HiMAT < 27 gained greater benefit from ballistic training: 6 points (1 to 10) on the HiMAT. CONCLUSION: This randomised trial shows that ballistic resistance training has a similar or better effect on mobility than non-ballistic training in people with traumatic brain injury. It may be better targeted towards those with more severe mobility limitations. TRIAL REGISTRATION: ACTRN12611001098921.

Incomplete chimerism following myeloablative and anti-thymocyte globulin-conditioned hematopoietic cell transplantation is a risk factor for relapse and chronic graft-versus-host disease.

BACKGROUND AIMS: The value of routine chimerism determination after myeloablative hematopoietic cell transplantation (HCT) is unclear, particularly in the setting of anti-thymocyte globulin (ATG)-based graft-versus-host disease (GVHD) prophylaxis. METHODS: Blood samples were collected at 3 months post-HCT from 558 patients who received myeloablative conditioning and ATG-based GVHD prophylaxis. Chimerism was assessed using multiplex polymerase chain reaction of short tandem repeats in sorted T cells (CD3+) and leukemia lineage cells (CD13+CD33+ for myeloid malignancies and CD19+ for B-lymphoid malignancies). ATG exposure was determined using a flow cytometry-based assay. The primary outcomes of interest were relapse and chronic GVHD (cGVHD). RESULTS: Incomplete (<95%) T-cell chimerism and leukemia lineage chimerism were present in 17% and 4% of patients, respectively. Patients with incomplete T-cell chimerism had a significantly greater incidence of relapse (36% versus 22%, subhazard ratio [SHR] = 2.03, P = 0.001) and lower incidence of cGVHD (8% versus 25%, SHR = 0.29, P < 0.001) compared with patients with complete chimerism. In multivariate modeling, patients with high post-transplant ATG area under the curve and any cytomegalovirus (CMV) serostatus other than donor/recipient seropositivity (non-D+R+) had an increased likelihood of incomplete T-cell chimerism. Patients with incomplete leukemia lineage chimerism had a significantly greater incidence of relapse (50% versus 23%, SHR = 2.70, P = 0.011) and, surprisingly, a greater incidence of cGVHD (45% versus 20%, SHR = 2.64, P = 0.003). CONCLUSIONS: High post-transplant ATG exposure and non-D+R+ CMV serostatus predispose patients to incomplete T-cell chimerism, which is associated with an increased risk of relapse. The increased risk of cGVHD with incomplete B-cell/myeloid chimerism is a novel finding that suggests an important role for recipient antigen-presenting cells in cGVHD pathogenesis.

Machine Learning Derived Lifting Techniques and Pain Self-Efficacy in People with Chronic Low Back Pain.

This paper proposes an innovative methodology for finding how many lifting techniques people with chronic low back pain (CLBP) can demonstrate with camera data collected from 115 participants. The system employs a feature extraction algorithm to calculate the knee, trunk and hip range of motion in the sagittal plane, Ward's method, a combination of K-means and Ensemble clustering method for classification algorithm, and Bayesian neural network to validate the result of Ward's method and the combination of K-means and Ensemble clustering method. The classification results and effect size show that Ward clustering is the optimal method where precision and recall percentages of all clusters are above 90, and the overall accuracy of the Bayesian Neural Network is 97.9%. The statistical analysis reported a significant difference in the range of motion of the knee, hip and trunk between each cluster, F (9, 1136) = 195.67, p < 0.0001. The results of this study suggest that there are four different lifting techniques in people with CLBP. Additionally, the results show that even though the clusters demonstrated similar pain levels, one of the clusters, which uses the least amount of trunk and the most knee movement, demonstrates the lowest pain self-efficacy.

Effects of Footwear on Anterior Cruciate Ligament Forces during Landing in Young Adult Females.

Rates of anterior cruciate ligament (ACL) rupture in young people have increased markedly over the past two decades, with females experiencing greater growth in their risk compared to males. In this study, we determined the effects of low- and high-support athletic footwear on ACL loads during a standardized drop-land-lateral jump in 23 late-/post-pubertal females. Each participant performed the task unshod, wearing low- (Zaraca, ASICS) or high- (Kayano, ASICS) support shoes (in random order), and three-dimensional body motions, ground-reaction forces, and surface electromyograms were synchronously acquired. These data were then used in a validated computational model of ACL loading. One-dimensional statistical parametric mapping paired t-tests were used to compare ACL loads between footwear conditions during the stance phase of the task. Participants generated lower ACL forces during push-off when shod (Kayano: 624 N at 71-84% of stance; Zaraca: 616 N at 68-86% of stance) compared to barefoot (770 N and 740 N, respectively). No significant differences in ACL force were observed between the task performed wearing low- compared to high-support shoes. Compared to barefoot, both shoe types significantly lowered push-off phase peak ACL forces, potentially lowering risk of ACL injury during performance of similar tasks in sport and recreation.