Fatigue during walking is a common complaint in cerebral palsy (CP). The primary purpose of this study is to investigate muscle fatigue from surface electromyography (sEMG) measurements after a ...treadmill-based fatigue protocol with increasing incline and speed in children with CP with drop foot. The secondary purpose is to investigate whether changes in sagittal kinematics of hip, knee and ankle occur after fatigue. Eighteen subjects with unilateral spastic CP performed the protocol while wearing their ankle-foot orthosis and scored their fatigue on the OMNI scale of perceived exertion. The median frequency (MF) and root mean square (RMS) were used as sEMG measures for fatigue and linear mixed effects model were applied. The MF was significantly decreased in fatigued condition, especially in the affected leg and in the tibialis anterior and peroneus longus muscle. The RMS did not change significantly in fatigued condition, while the OMNI fatigue score indicated patients felt really fatigued. No changes in sagittal kinematics of hip, knee and ankle were found using statistical non-parametric mapping. In conclusion, the current fatigue protocol seems promising in inducing fatigue in a population with CP with drop foot and it could be used to expand knowledge on muscle fatigue during walking in CP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract A more profound investigation about the responses in activity levels following pulmonary rehabilitation (PR) in patients with COPD is needed. We aimed to describe groups of patients with ...COPD according to patterns of change in physical activity and sedentary behaviour following PR. 90 patients with COPD (60% male; mean age 67 ± 8; median FEV1 47 (32–62) %pred) completed a comprehensive PR programme. A triaxial accelerometer was used to assess the time in sedentary behaviour, light activities and moderate-to-vigorous physical activity (MVPA). Additionally, exercise capacity, quality of life, and symptoms of anxiety and depression were assessed before and after PR. Six groups with different patterns of change in physical activity and sedentary behaviour were identified. The two most prevalent patterns were represented by good responders (increase in physical activity and reduction in sedentary behaviour, 34%) and poor responders (decrease in physical activity and increase in sedentary behaviour, 30%). Good responders had greater improvements in six-minute walk distance (6MWD) and symptoms of depression than poor responders ( P < 0.05 for all). Strong correlation was found between changes in sedentary behaviour and changes in light activities ( rs = −0.89; P < 0.0001). Changes in 6MWD correlated fairly with changes in sedentary behaviour ( rs = −0.26), light activities ( rs = 0.25), and MVPA ( rs = 0.24); P < 0.05 for all. Different patterns of change in activity levels following PR can be found in patients with COPD. Focusing on light physical activities might be a potential strategy to make patients less sedentary, but for this to be achieved prior (or at least parallel) improvements in functional capacity seem to be necessary.
Low amounts of physical activity (PA) and prolonged periods of sedentary activity are common in hospitalized patients. Objective PA monitoring is needed to prevent the negative effects of inactivity, ...but a suitable algorithm is lacking. The aim of this study is to optimize and validate a classification algorithm that discriminates between sedentary, standing, and dynamic activities, and records postural transitions in hospitalized patients under free-living conditions. Optimization and validation in comparison to video analysis were performed in orthopedic and acutely hospitalized elderly patients with an accelerometer worn on the upper leg. Data segmentation window size (WS), amount of PA threshold (PA Th) and sensor orientation threshold (SO Th) were optimized in 25 patients, validation was performed in another 25. Sensitivity, specificity, accuracy, and (absolute) percentage error were used to assess the algorithm's performance. Optimization resulted in the best performance with parameter settings: WS 4 s, PA Th 4.3 counts per second, SO Th 0.8 g. Validation showed that all activities were classified within acceptable limits (>80% sensitivity, specificity and accuracy, ±10% error), except for the classification of standing activity. As patients need to increase their PA and interrupt sedentary behavior, the algorithm is suitable for classifying PA in hospitalized patients.
Newly diagnosed patients with chronic myeloid leukaemia (CML) are currently treated with tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib or dasatinib. However, incomplete eradication of ...residual disease is a general problem of long-term TKI therapy. Activation of mouse haematopoietic stem cells by interferon-α (IFNα) stimulated the discussion of whether a combination treatment leads to accelerated eradication of the CML clone.
We base our simulation approach on a mathematical model describing human CML as a competition phenomenon between normal and malignant cells. We amend this model to incorporate the description of IFNα activity and simulate different scenarios for potential treatment combinations.
We demonstrate that the overall sensitivity of CML stem cells to IFNα activation is a crucial determinant for the benefit of a potential combination therapy. We furthermore show that pulsed IFNα together with continuous TKI administration is the most promising strategy for a combination treatment in which the therapeutic benefit prevails adverse side effects.
Our modelling approach is a highly beneficial tool to quantitatively address the competition between normal and leukaemic haematopoiesis in treated CML patients. We derive testable predictions for different experimental settings that are suggested before the clinical implementation of the combination treatment.
Tumor markers that are related to hypoxia, proliferation, DNA damage repair and stem cell-ness, have a prognostic value in advanced stage HNSCC patients when assessed individually. Here we aimed to ...evaluate and validate this in a multifactorial context and assess interrelation and the combined role of these biological factors in determining chemo-radiotherapy response in HPV-negative advanced HNSCC.
RNA sequencing data of pre-treatment biopsy material from 197 HPV-negative advanced stage HNSCC patients treated with definitive chemoradiotherapy was analyzed. Biological parameter scores were assigned to patient samples using previously generated and described gene expression signatures. Locoregional control rates were used to assess the role of these biological parameters in radiation response and compared to distant metastasis data. Biological factors were ranked according to their clinical impact using bootstrapping methods and multivariate Cox regression analyses that included clinical variables. Multivariate Cox regression analyses comprising all biological variables were used to define their relative role among all factors when combined.
Only few biomarker scores correlate with each other, underscoring their independence. The different biological factors do not correlate or cluster, except for the two stem cell markers CD44 and SLC3A2 (
= 0.4,
< 0.001) and acute hypoxia prediction scores which correlated with T-cell infiltration score, CD8
T cell abundance and proliferation scores (
= 0.52, 0.56, and 0.6, respectively with
< 0.001). Locoregional control association analyses revealed that chronic (Hazard Ratio (HR) = 3.9) and acute hypoxia (HR = 1.9), followed by stem cell-ness (CD44/SLC3A2; HR = 2.2/2.3), were the strongest and most robust determinants of radiation response. Furthermore, multivariable analysis, considering other biological and clinical factors, reveal a significant role for EGFR expression (HR = 2.9,
< 0.05) and T-cell infiltration (CD8
T-cells: HR = 2.2,
< 0.05; CD8
T-cells/Treg: HR = 2.6,
< 0.01) signatures in locoregional control of chemoradiotherapy-treated HNSCC.
Tumor acute and chronic hypoxia, stem cell-ness, and CD8
T-cell parameters are relevant and largely independent biological factors that together contribute to locoregional control. The combined analyses illustrate the additive value of multifactorial analyses and support a role for EGFR expression analysis and immune cell markers in addition to previously validated biomarkers. This external validation underscores the relevance of biological factors in determining chemoradiotherapy outcome in HNSCC.
The use of β-agonists as growth promoters in cattle breeding is forbidden in many countries for reasons of fair trade and consumer protection. In recent years the use of liquid chromatography (LC) ...tandem mass spectrometry (MS/MS) has been shown to be the method of choice for the control of β-agonists. In this study an LC-MS/MS multiresidue analysis method is presented for trace analysis of 22 β-agonists. A truly generic concept has been designed based on mixed-mode solid-phase extraction and positive electrospray ionisation LC-MS/MS operated in the multiple reaction monitoring mode. This method allows application to a wide variety of sample matrices such as urine, feed and hair, following minor modifications to the analysis procedure only. The method features fit-for-purpose sensitivity in urine as shown by CCα and CCβ values of less than 0.2 and less than 0.5 μg/l respectively, for all β-agonists studied (terbutaline and reproterol, less than 0.3 and less than 1.0 respectively). Similar but semiquantitative application to feed and hair showed CCβ values of less than 10.0 and less than 5.0 μg/kg, respectively. A further simplification and improvement is demonstrated using Ultra Performance LC (UPLCtrade mark sign) and fast-switching MS/MS. The successful validation of this method following the latest EU requirements and its application to real samples demonstrate that a new versatile tool has been achieved for veterinary control of β-agonists.
Proton therapy is a radiation technique that yields less dose in normal tissues than photon therapy. In the Netherlands, proton therapy is reimbursed if the reduced dose to normal tissues is ...predicted to translate into a prespecified reduction in toxicity, based on nationally approved validated models. The aim of this paper is to present the development of a national indication protocol for proton therapy (NIPP) for model-based selection of breast cancer patients and to report on first clinical experiences.
A national proton therapy working group for breast cancer (PWG-BC) screened the literature for prognostic models able to estimate the individual risk of specific radiation-induced side-effects. After critical appraisal and selection of suitable models, a NIPP for breast cancer was written and subjected to comments by all stakeholders. The approved NIPP was subsequently introduced to select breast cancer patients who would benefit most from proton therapy.
The model of Darby et al. (N Engl J Med 2013; 368:987–82) was the only model fulfilling the criteria prespecified by the PWG-BC. The model estimates the relative risk of an acute coronary event (ACE) based on the mean heart dose. The absolute lifetime risk of ACE <80 years was calculated by applying this model to the Dutch absolute incidence of ACE for female and male patients, between 40 and 70 years at breast cancer radiotherapy, with/without cardiovascular risk factors. The NIPP was approved for reimbursement in January 2019. Based on a threshold value of a 2% absolute lower risk on ACE for proton therapy compared with photons, 268 breast cancer patients have been treated in the Netherlands with proton therapy between February 2019 and January 2021.
The NIPP includes a model that allows the estimation of the absolute risk on ACE <80 years based on mean heart dose. In the first 2 years, 268 breast cancer patients have been treated with proton therapy in The Netherlands.
•Selection protocol was determined for proton therapy for breast cancer patients.•Prediction of lifetime risk of acute coronary events based on mean heart dose.•About 3–4% of breast cancer patients are expected to benefit from proton therapy.
Abstract Introduction We retrospectively investigated the possible influence of a simultaneous integrated boost (SIB), hypofractionation and oncoplastic surgery on cosmetic outcome in 125 patients ...with stage I–II breast cancer treated with breast conserving therapy (BCT). Patients and methods The boost was given sequentially (55%) or by SIB (45%); fractionation was conventional (83%) or hypofractionated (17%); the surgical technique was a conventional lumpectomy (74%) or an oncoplastic technique (26%). We compared cosmetic results subjectively using a questionnaire independently completed by the patient and by the physician and objectively with the BCCT.core software. Independent-samples T-tests were used to compare outcome in different groups. Patients also completed the EORTC QLQ C30 and BR23. Results Univariate analyses indicated no significant differences of the cosmetic results (P ≤ 0.05) for the type of boost or fractionation. However, the conventional lumpectomy group scored significantly better than the oncoplastic group in the BCCT.core evaluation, without a significant difference in the subjective cosmetic evaluation. Quality of life outcome was in favour of SIB, hypofractionation and conventional surgery. Conclusion Our study indicates that the current RT techniques seem to be safe for cosmetic outcome and quality of life. Further investigation is needed to verify the possible negative influence of oncoplastic surgery on the cosmetic outcome and the quality of life as this technique is especially indicated for patients with an unfavourable tumour/breast volume ratio.
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