Real-world data confirming the efficacy and safety of decitabine in acute myeloid leukaemia - results from a retrospective Belgian registry study.

Objectives: Currently, there is no standard treatment for patients with acute myeloid leukaemia (AML) ineligible for standard induction chemotherapy (IC). This study aimed to report real-world evidence data on the efficacy and safety of decitabine in this patient group.Methods: This study was a Belgian, retrospective, non-interventional, multicentre registry of patients ≥ 65 years, with newly-diagnosed de novo or secondary AML ineligible for IC. Patients were treated according to routine clinical practice. Overall survival (OS), progression-free survival (PFS) and transfusion independence for ≥8 consecutive weeks were evaluated.Results: Forty-five patients were enrolled, including 67% (n = 30) with secondary AML. Median OS and PFS were 7.3 months (95% CI: 2.2-11.1) and 4.1 months (95% CI: 2.1-7.6) respectively. A subpopulation analysis showed that patients treated with ≥4 cycles (n = 21) had significantly better outcomes compared to patients receiving <4 cycles (median OS 17.5 vs 1.6 months; median PFS 17.5 vs. 1.4 months). Twenty-five percent and 58% of patients that were respectively RBC or platelet transfusion-dependent at baseline became transfusion independent during treatment.Conclusion: This real-world data confirms that decitabine can lead to transfusion independence and longer OS in AML patients, particularly after administering ≥4 cycles, as indicated in the summary of product characteristics.

Is knee neuromuscular activity related to anterior cruciate ligament injury risk? A pilot study.

BACKGROUND: There is limited evidence on neuromuscular risk factors for anterior cruciate ligament (ACL) injuries, with most work mainly focusing on hamstrings and quadriceps muscle strength. This prospective pilot study explored if neuromuscular activation patterns of the quadriceps and hamstrings during a drop vertical jump influence ACL injury risk. METHODS: Forty-six female athletes performed a drop vertical jump at baseline. Injuries were monitored throughout a one-year follow-up. Neuromuscular activation patterns of the vastus medialis, vastus lateralis, hamstrings medialis and hamstrings lateralis, and selected landing kinematic and kinetic profiles (knee flexion, knee abduction and hip flexion angles, and knee abduction moments), were compared between athletes who sustained a non-contact ACL injury and those who remained injury free. Electromyogram vector fields were created to represent neuromuscular activation patterns of muscle pairs around the knee joint rather than only considering individual muscle activations, and compared using Statistical Parametric Mapping. RESULTS: Four athletes sustained an ACL injury. Significantly greater {hamstrings medials, hamstrings lateralis}, {vastus lateralis, hamstrings lateralis} and {hamstrings lateralis, vastus medialis} activations, mainly due to greater hamstrings lateralis activation, were found in the injured group around peak loading and just before take-off (P < 0.001). No group differences were found in knee flexion, knee abduction and hip flexion angles, or knee abduction moments. CONCLUSIONS: This pilot study revealed initial evidence that athletes already showed altered neuromuscular activation patterns prior to sustaining an ACL injury, namely increased lateral and posterior muscle activations.

Treatment continuation of four long-acting antipsychotic medications in the Netherlands and Belgium: A retrospective database study.

Achieving greater continuation of treatment is a key element to improve treatment outcomes in schizophrenia patients. However, reported treatment continuation can differ markedly depending on the study design. In a retrospective setting, treatment continuation remains overall poor among patients using antipsychotics. This study aimed to document the difference in treatment continuation between four long-acting injectable antipsychotics based on the QuintilesIMS LRx databases, national, longitudinal, panel based prescription databases of retail pharmacies, in the Netherlands and Belgium. Paliperidone palmitate once monthly, risperidone microspheres, haloperidol decanoate, and olanzapine pamoate were studied. This study demonstrated significantly higher treatment continuation of paliperidone palmitate once monthly compared to risperidone microspheres (p-value<0,01) and haloperidol decanoate (p-value<0,01) in both countries, a significantly higher treatment continuation of paliperidone palmitate once monthly compared to olanzapine pamoate in the Netherlands (p-value<0,01), and a general trend towards better treatment continuation versus olanzapine pamoate in Belgium. Analysing the subgroup of patients without previous exposure to long-acting antipsychotic treatment revealed the positive impact of previous exposure on treatment continuation with a subsequent long acting treatment. Additionally, the probability of restarting the index therapy was higher among patients treated with paliperidone palmitate once monthly compared to patients treated with risperidone microspheres and haloperidol decanoate. The data source used and the methodology defined ensured for the first time a comparison of treatment continuation in a non-interventional study design for the four long-acting injectable antipsychotics studied.

Knee and Hip Joint Kinematics Predict Quadriceps and Hamstrings Neuromuscular Activation Patterns in Drop Jump Landings.

PURPOSE: The purpose was to assess if variation in sagittal plane landing kinematics is associated with variation in neuromuscular activation patterns of the quadriceps-hamstrings muscle groups during drop vertical jumps (DVJ). METHODS: Fifty female athletes performed three DVJ. The relationship between peak knee and hip flexion angles and the amplitude of four EMG vectors was investigated with trajectory-level canonical correlation analyses over the entire time period of the landing phase. EMG vectors consisted of the {vastus medialis(VM),vastus lateralis(VL)}, {vastus medialis(VM),hamstring medialis(HM)}, {hamstring medialis(HM),hamstring lateralis(HL)} and the {vastus lateralis(VL),hamstring lateralis(HL)}. To estimate the contribution of each individual muscle, linear regressions were also conducted using one-dimensional statistical parametric mapping. RESULTS: The peak knee flexion angle was significantly positively associated with the amplitudes of the {VM,HM} and {HM,HL} during the preparatory and initial contact phase and with the {VL,HL} vector during the peak loading phase (p<0.05). Small peak knee flexion angles were significantly associated with higher HM amplitudes during the preparatory and initial contact phase (p<0.001). The amplitudes of the {VM,VL} and {VL,HL} were significantly positively associated with the peak hip flexion angle during the peak loading phase (p<0.05). Small peak hip flexion angles were significantly associated with higher VL amplitudes during the peak loading phase (p = 0.001). Higher external knee abduction and flexion moments were found in participants landing with less flexed knee and hip joints (p<0.001). CONCLUSION: This study demonstrated clear associations between neuromuscular activation patterns and landing kinematics in the sagittal plane during specific parts of the landing. These findings have indicated that an erect landing pattern, characterized by less hip and knee flexion, was significantly associated with an increased medial and posterior neuromuscular activation (dominant hamstrings medialis activity) during the preparatory and initial contact phase and an increased lateral neuromuscular activation (dominant vastus lateralis activity) during the peak loading phase.

Postural Stability During Single-Leg Stance: A Preliminary Evaluation of Noncontact Lower Extremity Injury Risk.

Study Design Controlled laboratory study with a prospective cohort design. Background Postural stability deficits during single-leg stance have been reported in persons with anterior cruciate ligament (ACL) injury, ACL reconstruction, and chronic ankle instability. It remains unclear whether impaired postural stability is a consequence or cause of these injuries. Objectives To prospectively investigate whether postural stability deficits during single-leg stance predict noncontact lower extremity injuries. Methods Fifty injury-free female athletes performed a transition task from double-leg stance to single-leg stance with eyes closed. Center-of-pressure displacement, the main outcome variable, was measured during the first 3 seconds after the time to a new stability point was reached during single-leg stance. Noncontact lower extremity injuries were recorded at a 1-year follow-up. Results Six participants sustained a noncontact ACL injury or ankle sprain. Center-of-pressure displacement during the first 3 seconds after the time to a new stability point was significantly increased in the injured (P = .030) and noninjured legs (P = .009) of the injured group compared to the respective matched legs of the noninjured group. The area under the receiver operating characteristic curve (AUC) analysis revealed significant discriminative accuracy between groups for the center-of-pressure displacement during the first 3 seconds after the time to a new stability point of the injured (AUC = 0.814, P = .015) and noninjured legs (AUC = 0.897, P = .004) of the injured group compared to the matched legs of the noninjured group. Conclusion This preliminary study suggests that postural stability measurements during the single-leg stance phase of the double- to single-leg stance transition task may be a useful predictor of increased risk of noncontact lower extremity injury. Further research is indicated. Level of Evidence Prognosis, level 4. J Orthop Sports PhysTher 2016;46(8):650-657. Epub 3 Jul 2016. doi:10.2519/jospt.2016.6278.

Biomechanical and neuromuscular adaptations during the landing phase of a stepping-down task in patients with early or established knee osteoarthritis.

BACKGROUND: To compare the knee joint kinematics, kinetics and EMG activity patterns during a stepping-down task in patients with knee osteoarthritis (OA) with control subjects. METHODS: 33 women with knee OA (early OA, n=14; established OA n=19) and 14 female control subjects performed a stepping-down task from a 20cm step. Knee joint kinematics, kinetics and EMG activity were recorded on the stepping-down leg during the loading phase. RESULTS: During the stepping-down task patients with established knee OA showed greater normalized medial hamstrings activity (p=0.034) and greater vastus lateralis-medial hamstrings co-contraction (p=0.012) than controls. Greater vastus medialis-medial hamstrings co-contraction was found in patients with established OA compared to control subjects (p=0.040) and to patients with early OA (p=0.023). Self-reported knee instability was reported in 7% and 32% of the patients with early and established OA, respectively. CONCLUSIONS: The greater EMG co-activity found in established OA might suggest a less efficient use of knee muscles or an attempt to compensate for greater knee laxity usually present in patients with established OA. In the early stage of the disease, the biomechanical and neuromuscular control of stepping-down is not altered compared to healthy controls.

Can two-dimensional measured peak sagittal plane excursions during drop vertical jumps help identify three-dimensional measured joint moments?

BACKGROUND: Less optimal sagittal plane movement patterns are believed to increase knee injury risk in female athletes. To facilitate clinical screening with a user-friendly method, the purpose of the present study was to examine the temporal relationships between two-dimensional measured sagittal plane kinematics and three-dimensional joint moments during the double-leg drop vertical jump (DVJ) and single-leg DVJ (SLDVJ). METHODS: Fifty injury-free female athletes were tested. Maximal excursions of hip flexion, knee flexion and ankle dorsiflexion were measured through two-dimensional video analysis. Three-dimensional motion and ground reaction forces were recorded to calculate external hip flexion, knee flexion and knee abduction moments during the entire stance phase of DVJ and SLDVJ. One-dimensional statistical parametric mapping was used to examine relationships between peak two-dimensional kinematic variables and three-dimensional moment profiles. RESULTS: Hip flexion was significantly related to the hip and knee flexion moment for both tests and knee abduction moment for DVJ during the time frames corresponding with highest three-dimensional moments, while knee flexion was significantly related to the hip flexion moment during these time frames. No significant relationships were found for ankle dorsiflexion with any of the joint moments. CONCLUSIONS: Two-dimensional measured sagittal plane hip flexion angles at the deepest landing position were associated with peak joint moments of the hip and knee during DVJ and SLDVJ, while the amount of knee flexion was only associated with the hip flexion moment. Assessment of knee injury risk with two-dimensional video analysis could benefit from measuring maximal hip flexion, more so than knee flexion.

Can two-dimensional video analysis during single-leg drop vertical jumps help identify non-contact knee injury risk? A one-year prospective study.

BACKGROUND: Previous studies showed that the amount of hip flexion and the combination of knee valgus and lateral trunk motion, measured with two-dimensional video analysis, were related to three-dimensional measured knee joint moments during single-leg drop vertical jumps, but it remains unclear whether these measurements can be used to identify non-contact knee injury risk. METHODS: Fifty injury-free female athletes participated in the study. Two-dimensional video analysis was used to measure hip flexion, knee valgus and lateral trunk motion angles during single-leg drop vertical jumps. Time loss non-contact knee injuries were registered during a one-year follow-up. Independent t-tests and receiver operating characteristic analysis were used to analyze the predictive ability of the two-dimensional angles. FINDINGS: Seven participants sustained a time loss non-contact knee injury. Hip flexion was not significantly different between groups (P>.05). The combination of knee valgus and lateral trunk motion was significantly smaller in the injured (P=.036) and non-injured legs (P=.009) of the future injured group compared with the respective matched leg of the non-injured group. The receiver operating characteristic analysis showed a significant discriminative accuracy between groups for the combination of knee valgus and lateral trunk motion of the uninjured leg of the future injured group with the matched leg of the non-injured group (area under curve=0.803; P=.012). INTERPRETATION: The measurement of a combination of increased knee valgus and ipsilateral trunk motion during the single-leg drop vertical jump with two-dimensional video analysis can be used to help identify female athletes with increased non-contact knee injury risk.

How reliable are knee kinematics and kinetics during side-cutting manoeuvres?

INTRODUCTION: Side-cutting tasks are commonly used in dynamic assessment of ACL injury risk, but only limited information is available concerning the reliability of knee loading parameters. The aim of this study was to investigate the reliability of side-cutting data with additional focus on modelling approaches and task execution variables. METHODS: Each subject (n=8) attended six testing sessions conducted by two observers. Kinematic and kinetic data of 45° side-cutting tasks was collected. Inter-trial, inter-session, inter-observer variability and observer/trial ratios were calculated at every time-point of normalised stance, for data derived from two modelling approaches. Variation in task execution variables was regressed against that of temporal profiles of relevant knee data using one-dimensional statistical parametric mapping. RESULTS: Variability in knee kinematics was consistently low across the time-series waveform (≤5°), but knee kinetic variability was high (31.8, 24.1 and 16.9 Nm for sagittal, frontal and transverse planes, respectively) in the weight acceptance phase of the side-cutting task. Calculations conveyed consistently moderate-to-good measurement reliability. Inverse kinematic modelling reduced the variability in sagittal (∼6 Nm) and frontal planes (∼10 Nm) compared to direct kinematic modelling. Variation in task execution variables did not explain any knee data variability. CONCLUSION: Side-cutting data appears to be reliably measured, however high knee moment variability exhibited in all planes, particularly in the early stance phase, suggests cautious interpretation towards ACL injury mechanics. Such variability may be inherent to the dynamic nature of the side-cutting task or experimental issues not yet known.

Dynamic Neuromuscular Control of the Lower Limbs in Response to Unexpected Single-Planar versus Multi-Planar Support Perturbations in Young, Active Adults.

PURPOSE: An anterior cruciate ligament (ACL) injury involves a multi-planar injury mechanism. Nevertheless, unexpected multi-planar perturbations have not been used to screen athletes in the context of ACL injury prevention yet could reveal those more at risk. The objective of this study was to compare neuromuscular responses to multi-planar (MPP) and single-planar perturbations (SPP) during a stepping-down task. These results might serve as a basis for future implementation of external perturbations in ACL injury screening programs. METHODS: Thirteen young adults performed a single leg stepping-down task in eight conditions (four MPP and four SPP with a specified amplitude and velocity). The amplitudes of vastus lateralis (VL), vastus medialis (VM), hamstrings lateralis (HL), hamstrings medialis (HM) EMG activity, medio-lateral and anterior-posterior centre of mass (COM) displacements, the peak knee flexion and abduction angles were compared between conditions using an one-way ANOVA. Number of stepping responses were monitored during all conditions. RESULTS: Significantly greater muscle activity levels were found in response to the more challenging MPP and SPP compared to the less challenging conditions (p < 0.05). No differences in neuromuscular activity were found between the MPP conditions and their equivalents in the SPP. Eighteen stepping responses were monitored in the SPP versus nine in the MPP indicating that the overall neuromuscular control was even more challenged during the SPP which was supported by greater COM displacements in the SPP. CONCLUSION: The more intense MPP and SPP evoked different neuromuscular responses resulting in greater muscle activity levels compared to small perturbations. Based on the results of COM displacements and based on the amount of stepping responses, dynamic neuromuscular control of the knee joint appeared less challenged during the MPP. Therefore, future work should investigate extensively if other neuromuscular differences (i.e. co-activation patterns and kinetics) exist between MPP and SPP. In addition, future work should examine the influence on the neuromuscular control of the magnitude of the perturbations and the magnitude of stepping height and stepping distance.

The reliability and validity of the measurement of lateral trunk motion in two-dimensional video analysis during unipodal functional screening tests in elite female athletes.

OBJECTIVE: To investigate the reliability and validity of the measurement of lateral trunk motion (LTM) in two-dimensional (2D) video analysis of unipodal functional screening tests. DESIGN: Observational study. SETTING: Research laboratory. PARTICIPANTS: Forty-three injury-free female athletes. MAIN OUTCOME MEASURES: Knee valgus (KV) and lateral trunk motion (LTM) angles were measured with a standard digital camera during the single leg squat and the single leg drop vertical jump (SLDVJ). Three-dimensional motion analysis was used during the SLDVJ to measure peak external knee abduction moment (pKAM). Intraclass correlation coefficients were calculated to assess the intra- and intertester reliability of the LTM angle. Correlations between 2D angles and pKAM were calculated for the SLDVJ. RESULTS: Excellent intraclass correlation coefficients for the LTM angle were found within (0.99-1.00) and between testers (0.98-0.99). The sum of KV and LTM was significantly correlated with the pKAM during the SLDVJ for the dominant (r = -0.36; p = 0.017) and non-dominant leg (r = -0.32; p = 0.034), while either angle alone was not. CONCLUSIONS: LTM can be measured with excellent intra- and intertester reliability. The combination of KV and LTM was moderately associated with pKAM and thus including LTM may aid assessment of movement quality and injury risk.

How reliable are lower-limb kinematics and kinetics during a drop vertical jump?

PURPOSE: As drop vertical jumps (DVJ) are widely used as a screening task, the assessment of the reliability of lower-limb biomechanical parameters during DVJ is important. The aim of this study was to assess the reliability of the kinematic and kinetic peak values as well as of the waveforms for lower-limb parameters obtained with the Liverpool John Moores University biomechanical model (LJMU model) during performance of DVJ. METHODS: The reliability was analyzed by calculating the intertrial (o(trial)), intersession (o(sess)), and intertherapist (o(ther)) errors of hip and knee joint parameters in a repeated-measures design including two therapists and a total of six sessions. RESULTS: The results showed o(trial) that ranged from 1.1° to 3.5° for all peak kinematic parameters and from 3.6 to 12.9 N · m for all peak kinetic parameters. The o of the peak values ranged from 1.9° to 5.7° for all angles and from 5.4 to 19.8 N · m for the hip and knee joint moments in all planes. The o(sess) of the peak values ranged from 2.7° to 6.4° for all angles and from 5.8 to 22.4 N · m for all moments. Most of the kinematic and kinetic peak parameters had o(ther-trial) ≤ 2.0° and 4.3 N · m, respectively, suggesting a small extrinsic variability. Furthermore, the entire waveforms also showed a rather high o(trial) relative to other types of variability. CONCLUSIONS: The present findings indicated that DVJ kinetics and kinematics show small extrinsic variability. The reported errors are useful for clinical interpretation processes of DVJ performance as screening task for injury risk and rehabilitation outcome taking into consideration the different types of measurement error over time.