Validation of a scanning technique with minimal compression for measuring muscle volume with freehand 3D ultrasound.

Freehand 3D ultrasound (3D-US) is a promising technique for measuring muscle volume but it requires gel pads or water tanks to limit probe compression on the skin which makes it hard to use in clinical applications. Our objectives were to measure the effect of different compressions on muscle volume in order to assess the clinical applicability of a minimal compression method for lower limb muscles. 4 muscles of the lower limb on 15 healthy volunteers were scanned with a new commercial freehand 3D-US setup accessible to clinical experimentators. Each muscle was scanned with 3 levels of compression: standard compression, minimal compression and gel pad (method validated against MRI). Volume was calculated using software segmentation tools. Acquisitions and segmentations were done by the same examiner. There was a significant impact of standard compression on volume measurements, but no difference between minimal compression and gel pad. Standard compression underestimated volume with a mean bias of 16 mL. For minimal compression, 75 % of measured differences were below the predefined clinically acceptable limits of 10 mL. Mean bias for this method was 1.1 mL. In conclusion, standard compression in freehand 3D-US induces a systematic bias in volume calculations. But, with a trained examiner and the necessary precautions to minimize compression, this bias could be abolished and become acceptable in clinical applications. When a high accuracy is required, gel pads could still be important to consider.

Use of analgesics in France, following dextropropoxyphene withdrawal.

BACKGROUND: In 2009, the European Medicines Agency recommended withdrawal of dextropropoxyphene (DXP); in March 2011 it was withdrawn from the market in France. Up until that time the combination dextropropoxyphene-paracetamol (DXP/PC) was widely used for analgesia. At withdrawal, French regulators recommended that DXP/PC be replaced by other step 2 analgesics, i.e. tramadol, codeine, or opium-containing drugs, or by PC for a weak level of pain. To investigate prescribing behaviours after DXP/PC withdrawal, dispensations of analgesics before and after withdrawal were analysed. METHODS: Aggregated dispensation data of analgesics prescribed between January 2009 and December 2012 in the Rhône-Alpes region were obtained from the general health insurance claims data; changes in analgesic dispensation over time were analysed with the ATC/DDD methodology. Pre (Jan-June 2009) and post-withdrawal (Jan-June 2012) changes of DDDs where computed for each analgesic step. RESULTS: The dispensations of DXP/PC experienced a two-step decrease until 2011. Over the withdrawal period 2009-2012, there was a 14% decrease in the overall use of analgesic (from 109 to 94 DDDs), while the use of step 2 analgesics declined by 46% (- 22 DDDs, from 47 to 25 DDDs). This latter decline included a cessation of use of DXP/PC (29 DDDs in 2009) that were only in part (+ 7 DDDs, from 18 to 25 DDDs) compensated by increased use of codeine, tramadol and opium, in monotherapy or combined with PC. For step 1 analgesics, use increased with 9%, mostly PC (+ 8 DDDs, from 31 to 39 DDDs). Step 3 analgesics dispensations remained largely unchanged over this period (around 3 DDDs). CONCLUSIONS: In the Rhône-Alpes region, DXP/PC withdrawal was accompanied in part by an increased use of same level analgesics, and in part by an increased use of PC in monotherapy. The extent of DXP/PC use before withdrawal, and the increased use of PC after DXP withdrawal, underline the complexity of pain management.

Mathematical model of T-cell lymphoblastic lymphoma: disease, treatment, cure or relapse of a virtual cohort of patients.

T lymphoblastic lymphoma (T-LBL) is a rare type of lymphoma with a good prognosis with a remission rate of 85%. Patients can be completely cured or can relapse during or after a 2-year treatment. Relapses usually occur early after the remission of the acute phase. The median time of relapse is equal to 1 year, after the occurrence of complete remission (range 0.2-5.9 years) (Uyttebroeck et al., 2008). It can be assumed that patients may be treated longer than necessary with undue toxicity.The aim of our model was to investigate whether the duration of the maintenance therapy could be reduced without increasing the risk of relapses and to determine the minimum treatment duration that could be tested in a future clinical trial.We developed a mathematical model of virtual patients with T-LBL in order to obtain a proportion of virtual relapses close to the one observed in the real population of patients from the EuroLB database. Our simulations reproduced a 2-year follow-up required to study the onset of the disease, the treatment of the acute phase and the maintenance treatment phase.

Efficacy and safety of DPP-4 inhibitors in patients with type 2 diabetes: Meta-analysis of placebo-controlled randomized clinical trials.

BACKGROUND: Guidelines for type 2 diabetes (T2D) recommend reducing HbA1c through lifestyle interventions and glucose-lowering drugs (metformin, then combination with dipeptidyl peptidase-4 inhibitors [DPP-4Is] among other glucose-lowering drugs). However, no double-blind randomized clinical trial (RCT) compared with placebo has so far demonstrated that DDP-4Is reduce micro- and macrovascular complications in T2D. Moreover, the safety of DPP-4Is (with increased heart failure and acute pancreatitis) remains controversial. METHODS: A systematic review of the literature (PubMed, Cochrane Library Central Register of Controlled Trials [CENTRAL] and https://clinicaltrials.gov), including all RCTs vs placebo published up to May 2015 and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), published June 2015, was performed. Primary endpoints were all-cause mortality and death from cardiovascular causes; secondary endpoints were macrovascular and microvascular events. Safety endpoints were acute pancreatitis, pancreatic cancer, serious adverse events and severe hypoglycaemia. RESULTS: A total of 36 double-blind RCTs were included, allowing analyses of 54,664 patients. There were no significant differences in all-cause mortality (RR=1.03, 95% confidence interval [CI]=0.95-1.12), cardiovascular mortality (RR=1.02, 95% CI=0.92-1.12), myocardial infarction (RR=0.98, 95% CI=0.89-1.08), strokes (RR=1.02, 95% CI=0.88-1.17), renal failure (RR=1.06, 95% CI=0.88-1.27), severe hypoglycaemia (RR=1.14, 95% CI=0.95-1.36) and pancreatic cancer (RR=0.54, 95% CI=0.28-1.04) with the use of DPP-4Is. However, DDP-4Is were associated with an increased risk of heart failure (RR=1.13, 95% CI=1.01-1.26) and of acute pancreatitis (RR=1.57, 95% CI=1.03-2.39). CONCLUSION: There is no significant evidence of short-term efficacy of DPP-4Is on either morbidity/mortality or macro-/microvascular complications in T2D. However, there are warning signs concerning heart failure and acute pancreatitis. This suggests a great need for additional relevant studies in future.

Factors associated with 12 week case-fatality in Staphylococcus aureus bacteraemia: a prospective cohort study.

Staphylococcus aureus bacteraemia (SAB) is a frequent and deadly disease. Given the lack of a randomized trial, optimal first-line antibiotic treatment is still debated. Our aim was to identify prognostic factors in SAB patients and to analyse the impact of first-line antibiotics. The VIRSTA prospective cohort study was conducted in eight tertiary care centres in France. Consecutive incident adults in whom a blood culture drawn in participating centres grew S. aureus between April 2009 and October 2011 were prospectively followed for 12 weeks. Factors associated with 12-week case-fatality were identified by multivariate logistic regression. We enrolled 2091 patients and analysed survival in 1972 (median age 67.8 years, interquartile range 55.5-78.9; females 692/1972, 35.1%). SAB was nosocomial or healthcare-related in 1372/1972 (69.6%) of cases and the primary focus was unknown in 414/1972 (21.0%) of cases. Week 12 case-fatality rate was 671/1972 (34.0%). The main independent prognostic factors on multivariate analysis were age (adjusted OR by 10-year increment 1.56; 95% CI 1.44-1.69), septic shock (OR 5.11; 95% CI 3.84-6.80), metastatic cancer (OR 4.28; 95% CI 2.88-6.38), and unknown primary focus (OR 2.62; 95% CI 2.02-3.41). In the 1538 patients with methicillin-sensitive S. aureus (MSSA) bacteraemia, first-line empiric antistaphylococcal penicillins (OR 0.40; 95% CI 0.17-0.95) and vancomycin (OR 0.37; 95% CI 0.17-0.83), alone or combined with an aminoglycoside, were associated with better outcome compared with other antibiotics. There are few modifiable prognostic factors for SAB. Initiating empiric antibiotics with antistaphylococcal penicillins or vancomycin may be associated with better outcome in MSSA bacteraemia.

Dynamic changes of depolarizing GABA in a computational model of epileptogenic brain: Insight for Dravet syndrome.

Abnormal reemergence of depolarizing GABAA current during postnatal brain maturation may play a major role in paediatric epilepsies, Dravet syndrome (DS) being among the most severe. To study the impact of depolarizing GABA onto distinct patterns of EEG activity, we extended a neural mass model as follows: one sub-population of pyramidal cells was added as well as two sub-populations of interacting interneurons, perisomatic-projecting interneurons (basket-like) with fast synaptic kinetics GABAA (fast, I1) and dendritic-projecting interneurons with slow synaptic kinetics GABAA (slow, I2). Basket-like cells were interconnected to reproduce mutual inhibition mechanisms (I1➔I1). The firing rate of interneurons was adapted to mimic the genetic alteration of voltage gated sodium channels found in DS patients, SCN1A(+/-). We implemented the "dynamic depolarizing GABAA" mediated post-synaptic potential in the model, as some studies reported that the chloride reversal potential can switch from negative to more positive value depending on interneuron activity. The "shunting inhibition" promoted by GABAA receptor activation was also implemented. We found that increasing the proportion of depolarizing GABAA mediated IPSP (I1➔I1 and I1➔P) only (i.e., other parameters left unchanged) was sufficient to sequentially switch the EEG activity from background to (1) interictal isolated polymorphic epileptic spikes, (2) fast onset activity, (3) seizure like activity and (4) seizure termination. The interictal and ictal EEG patterns observed in 4 DS patients were reproduced by the model via tuning the amount of depolarizing GABAA postsynaptic potential. Finally, we implemented the modes of action of benzodiazepines and stiripentol, two drugs recommended in DS. Both drugs blocked seizure-like activity, partially and dose-dependently when applied separately, completely and with a synergic effect when combined, as has been observed in DS patients. This computational modeling study constitutes an innovative approach to better define the role of depolarizing GABA in infantile onset epilepsy and opens the way for new therapeutic hypotheses, especially in Dravet syndrome.

Is HbA1c a valid surrogate for macrovascular and microvascular complications in type 2 diabetes?

Recent recommendations regarding type 2 diabetes (T2D) patients' treatments have focused on personalizing glycosylated haemoglobin (HbA1c) targets. Because the relationship between HbA1c and diabetes prognosis has been established from large prospective cohorts, it is valid to question the extrapolation from population-based risk reduction estimations to individual predictions. Our study aimed to investigate the relationship between HbA1c reductions and clinical outcomes in randomized controlled trials (RCTs), using a meta-regression approach. Included were RCTs comparing intensive vs. standard glucose-lowering regimens for cardiovascular events and microvascular complications in T2D patients. Eight studies (33,396 patients) providing data for HbA1c reductions were found. In our meta-regression, HbA1c decreases were not significantly associated with reductions in our main study outcomes: total and cardiovascular mortality. They were also not associated with any of the secondary endpoints, including myocardial infarction, stroke and severe hypoglycaemia. Sensitivity analysis showed a significant correlation only between HbA1c-lowering and severe hypoglycaemia (P = 0.014). Meta-regression analysis could find no significant association between HbA1c-lowering and a decrease in clinical outcomes, thereby questioning the use of HbA1c as a surrogate outcome for T2D-related complications. Thus, RCTs vs. placebo are urgently required to evaluate the risk-benefit ratios of therapeutic strategies beyond HbA1c control in T2D patients.

Model of mucociliary clearance in cystic fibrosis lungs.

Mucus clearance is a primary innate defense mechanism in the human airways. Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF is characterized by dehydration of airway surface liquid and impaired mucociliary clearance. As a result, microorganisms are not efficiently removed from the airways, and patients experience chronic pulmonary infections and inflammation. We propose a new physiologically based mathematical model of muco-ciliary transport consisting of the two major components of the mucociliary clearance system: (i) periciliary liquid layer (PCL) and (ii) mucus layer. We study mucus clearance under normal conditions and in CF patients. Restoring impaired clearance of airway secretions in one of the major goals of therapy in patients with CF. We consider the action of the aerosolized and inhaled medication dornase alfa, which reduces the viscosity of cystic fibrosis mucus, by selectively cleaving the long DNA strands it contains. The results of the model simulations stress the potential relevance of the location of the drug deposition in the central or peripheral airways. Mucus clearance was increased in case the drug was primarily deposited peripherally, i.e. in the small airways.

Gastrointestinal tolerance of erythritol-containing beverage in young children: a double-blind, randomised controlled trial.

BACKGROUND/OBJECTIVE: To determine gastrointestinal (GI) responses and maximum tolerated dose of erythritol in young children given as a single oral dose in a 250-ml non-carbonated fruit-flavoured beverage in between meals. This is a multicentre double-blind study with sequential design for multiple dose groups and randomised crossover for comparators of placebo vs dose. SUBJECTS/METHODS: A total of 185 healthy young children aged 4-6 years were recruited at three clinical investigation centres after informed consent of both parents; 184 children completed the study. Children were included in one of the four dose groups (5, 15, 20 or 25 g erythritol) and exposed randomly to only one single dose vs an isosweet sucrose placebo. After consumption in the clinic and an observation period, GI symptoms and stooling patterns were recorded during the next 48 h. RESULTS: Statistically significantly more episodes of diarrhoea and/or severe GI symptoms were observed in the 20 and 25 g groups compared with placebo, but not in the 5 and 15 g groups. Stool consistency, as measured by Bristol stool scale, was lower in the 15-, 20- and 25 g groups for the first 24 -h period, but not at later time points. Incidences of nausea, vomiting, borborygmi, excess flatus and abdominal pain were not significantly different from the placebo controls at all doses of erythritol. CONCLUSIONS: Rapid ingestion of up to and including 15 g (6% w/v) of erythritol in a beverage in between meals by young children aged 4-6 years was well tolerated. The no observed effect level for diarrhoea and/or severe GI symptoms was 15 g (0.73 g/kg body weight (bw)). Children appeared not to be more sensitive to the GI effects of erythritol than published for adults on a g/kg bw basis.

Effects of pharmacological treatments on micro- and macrovascular complications of type 2 diabetes: what is the level of evidence?

Antidiabetic drugs for type 2 diabetes receive marketing authorization if they show efficacy in reducing levels of HbA(1c). However, efficacy on this biological criterion does not necessarily reflect clinical benefit to patients. Several randomized clinical trials have shown that antidiabetic drugs reduce HbA(1c) without a corresponding reduction in clinical events. This suggests a need to focus on the clinical effectiveness (morbimortality criteria) of our available antidiabetic drugs. In this non-extensive review of the literature, it was found that none of the current antidiabetic drugs have clearly proven their superiority over placebo in the gold standard double-blind randomized clinical trials. Thus, in 2013, the level of evidence for the clinical efficacy of antidiabetic drugs is disappointing and does not support the millions of prescriptions being written for them.

Congenital toxoplasma infection: monthly prenatal screening decreases transmission rate and improves clinical outcome at age 3 years.

BACKGROUND: Toxoplasma infection during pregnancy exposes the fetus to risks of congenital infection and sequelae that depend heavily on gestational age (GA) at time of infection. Accurate risk estimates by GA are necessary to counsel parents and improve clinical decisions. METHODS: We analyzed data from pregnant women diagnosed with acute Toxoplasma infection in Lyon (France) from 1987 to 2008 and assessed how the risks of congenital toxoplasmosis and of clinical signs at age 3 years vary depending on GA at the time of maternal infection. RESULTS: Among 2048 mother-infant pairs, 93.2% of mothers received prenatal treatment and 513 (24.7%) fetuses were infected. Because of a significant reduction in risk since 1992 when monthly screening was introduced (59.4% vs 46.6% at 26 GA weeks; P = .038), probabilities of infection were estimated on the basis of maternal infections diagnosed after mid-1992 (n = 1624). Probabilities of congenital infection were <10% for maternal infections before 12 weeks of gestation, rose to 20.0% at 19 weeks, and then continued increasing to 52.3% and almost 70% at 28 and 39 GA weeks, respectively. Because of a significant reduction in risk of clinical signs of congenital toxoplasmosis in infected children born from mothers diagnosed after 1995 when polymerase chain reaction testing on amniotic fluid was initiated (87/794 vs 46/1150; P = .012), probabilities of clinical signs at 3 years were estimated based on 1015 maternal infections diagnosed after 1995 including 207 infected children, with symptoms in 46 (22.2%). CONCLUSIONS: These analyses demonstrated that introduction of monthly prenatal screening and improvement in antenatal diagnosis were associated with a significant reduction in the rate of congenital infection and a better outcome at 3 years of age in infected children. Our updated estimates will improve individual management and counseling in areas where genotype II Toxoplasma is predominant.

Efficacy of a home-based intervention programme on the physical activity level and functional ability of older people using domestic services: a randomised study.

OBJECTIVE: Our main objective was to assess whether a home-based program supervised by home helpers (HH) during their normal working hours can prevent excessive sedentariness (mainly maximum walking time and distance) and preserve functional status in elderly people at risk for frailty or disability and using domestic services. DESIGN: A four-month, open label, randomised trial with two groups called "prevention" and "control". SETTING: In the homes of study participants. PARTICIPANTS: The participants were all over 78 years old, lived independently at home, and received the visits of HHs at least once a week. INTERVENTION: The intervention combined a self-administered exercise program, with 10 g amino-acid supplementation under the supervision of HHs. MEASUREMENTS: Main outcome measures included physical activity (the PASE questionnaire), functional tests, nutritional and autonomy scores, and compliance (50% or more was considered satisfactory). Non-parametric methods were used for comparisons between the two groups. A linear regression model was fitted to assess the effect of the intervention on the relative variation of outcomes, adjusted for unbalanced baseline co-variables. RESULTS: One hundred and two persons (prevention n=53, control n=49) with a median age of 85 years were included. Their median Activities of Daily Living and Instrumental Activities of Daily Living (IADL) scores were 6 and 7 respectively. Twenty-three (44%) were good compliers for both interventions. The maximum walking time remained stable while decreasing by 25% in the control group (p=0.0015); and fewer participants had a worsened IADL score in the prevention group (p=0.05). The baseline IADL Score was significantly associated with good compliance to the prevention program (p=0.0011). In good compliers, maximum walking distance and maximum walking time increased by 29.15% (0.0 to 66.7) and 33.3% (-20.0 to 50.0) respectively. CONCLUSION: This study confirms the feasibility of a prevention program supervised by HHs, and some benefit from the intervention and identifies predictors for better compliance. It will help in the design of prevention trials for elderly people at risk for frailty.

Is tendon stiffness correlated to the dissipation coefficient?

The assessment of Achilles tendon mechanical properties in vivo has received much attention in the literature. Many studies investigated mechanical properties by assessing tendon stiffness. Despite tendon dissipative properties being representative of a storage-recoil process, its determination has received minimal attention in the literature. The aim of this study was to determine if Achilles tendon stiffness is associated with dissipative properties. The cross-sectional area, stiffness and dissipation coefficient of the Achilles tendon were measured in 35 subjects. No significant correlation was found between stiffness and the dissipation coefficient, irrespective of stiffness normalization with cross-sectional area (P > 0.05). Thus, it appears that both stiffness and dissipative properties must be assessed to determine the storage-recoil process capacities of the Achilles tendon in order to precisely characterize changes in the tendon mechanical properties after chronic interventions or rehabilitation programs.

Thigh muscle activities in elite rowers during on-water rowing.

This study analysed the muscle activity levels and patterns of the major thigh muscle activation during training sections at different intensities of on-water rowing. 9 experienced rowers performed 2 imposed-pace sections (B1 and B2) and 2 maximal-speed sections (start, 500 m) of on-water rowing. The knee angle, power output, mean torque and stroke rate were measured using specific instrumentation and were synchronised with surface electromyography signals of 5 superficial quadriceps and hamstring muscles. B1 and B2 sections were not significantly different regarding mechanical parameters and EMG activities, while the start phase induced large differences. The EMG patterns for B1, B2 were similar (cross-correlation coefficients (CC) ranged between 0.972-0.984) and the moderate CC found between both B1 and start (0.605-0.720) and B2 and start (0.629-0.720). Our results suggest that the hamstring muscles have a motor action and contribute to the power production during the leg drive. During an all-out 500 m section, a decrease in power and stroke rate was found (up to 20%). However, EMG patterns were not time shifted for all muscles. During the leg drive, the muscle activity levels of the quadriceps muscles were unchanged, while the activity of the hamstring muscles decreased.

[Design and evaluation of the quality of information written for scanner and magnetic resonance imaging in neuropediatrics]. / Conception et évaluation de la qualité d'une information écrite sur le scanner et l'imagerie par résonance magnétique en neuropédiatrie.

INTRODUCTION: We designed written information concerning two medical imaging techniques: the computed tomography scanner and the magnetic resonance imaging (MRI), and we evaluated the quality of the information in particular its readability. METHODS: Written information concerning scanner and MRI were elaborate starting from a reference frame based on a lexicon of the good practices. The written information sheets were initially reviewed by eight doctors, 45 nurses and by 26 couples of parents of hospitalized children, and finally by the communication and juridical services of our hospital. They were asked to improve the lexico-syntactic readability in order to increase the comprehension of the written information. Seventy-two couples of parents of hospitalized children who had not taken part of the protocol before evaluated the final version of the documents. The quality of the documents was evaluated using the scores of readability of Flesch and the Flesch-Kincaid, and a questionnaire of comprehension, managed before and after the delivery of written information. RESULTS: A total of 144 persons participated in the study. The number of right answers after reading written information increased by 38 % and by 35 % for the scanner and MRI information's respectively. Flesch and Flesch-Kincaid scores were not improved in the revised version of the written information compared to the first version. CONCLUSION: Although readability scores for information sheets were low, our results suggest that they brought information, which contributed to a better understanding of these two medical imaging techniques by parents.

Neuromuscular and muscle-tendon system adaptations to isotonic and isokinetic eccentric exercise.

OBJECTIVE: To present the properties of an eccentric contraction and compare neuromuscular and muscle-tendon system adaptations induced by isotonic and isokinetic eccentric trainings. SYNTHESIS: An eccentric muscle contraction is characterized by the production of muscle force associated to a lengthening of the muscle-tendon system. This muscle solicitation can cause micro lesions followed by a regeneration process of the muscle-tendon system. Eccentric exercise is commonly used in functional rehabilitation for its positive effect on collagen synthesis but also for resistance training to increase muscle strength and muscle mass in athletes. Indeed, eccentric training stimulates muscle hypertrophy, increases the fascicle pennation angle, fascicles length and neural activation, thus inducing greater strength gains than concentric or isometric training programs. Eccentric exercise is commonly performed either against a constant external load (isotonic) or at constant velocity (isokinetic), inducing different mechanical constraints. These different mechanical constraints could induce structural and neural adaptive strategies specific to each type of exercise. CONCLUSION: The literature tends to show that isotonic mode leads to a greater strength gain than isokinetic mode. This observation could be explained by a greater neuromuscular activation after IT training. However, the specific muscle adaptations induced by each mode remain difficult to determine due to the lack of standardized, comparative studies.

In vivo assessment of both active and passive parts of the plantarflexors series elastic component stiffness using the alpha method: a reliability study.

The aim of this study was to investigate the reliability of an in vivo adaptation of the short range stiffness experiment associated with the application of a mathematical model to determine the stiffness of both torque dependent and independent components of the plantarflexors series elastic component. Fourteen subjects participated in this study. The experimental protocol consisted of quickly moving the ankle joint in dorsiflexion during constant voluntary isometric plantarflexion at 7 submaximal torque levels. Relationships between joint stiffness and torque were established and the stiffness of both torque dependent and independent components were determined using the alpha method. The day-to-day reliability was assessed for joint stiffness and stiffness of both torque dependent and independent components (ICC higher than 0.88 and CVs lower than 6.0%). This method could then be used to better understand adaptive subjacent mechanisms to assess the effects of training protocols, and the rehabilitation of neuromuscular pathologies or traumatisms.

Improvements to Hoang et al.'s method for measuring passive length-tension properties of human gastrocnemius muscle in vivo.

While the passive mechanical properties of a musculo-articular complex can be determined using the relationship between the articular angle and the passive torque developed in resistance to motion, the properties of different structures of the musculo-articular complex cannot be easily assessed. Recently, an elegant method has been proposed to estimate the passive length-tension properties of gastrocnemius muscle-tendon unit (Hoang et al., 2005). In the present paper, two improvements of this method are proposed to decrease the number of parameters required to assess the passive length-tension relationship from 9 to 2. Furthermore, these two parameters have physical meaning as they represent a passive muscle-tendon stiffness index (alpha) and the muscle-tendon slack length (l(0)). alpha and l(0) are relevant clinical parameters to study the chronic effects of aging, training protocols or neuromuscular pathologies on the passive mechanical properties of the muscle-tendon unit. Eight healthy subjects performed passive loading/unloading cycles at 5 degrees /s with knee angle at 6 knee angles to assess the torque-angle relationships and to apply the modified method. Numerical optimization was used to minimize the squared error between the experimental and the modeled relationships. The experiment was performed twice to assess the reliability of alpha and l(0) across days. The results showed that the reliability of the two parameters was good (alpha: ICC=0.82, SEM=6.1m(-1), CV=6.3% and l(0): ICC=0.83, SEM=0.29 cm, CV=0.9%). Using a sensitivity analysis, it was shown that the numerical solution was unique. Overall, the findings may provide increased interest in the method proposed by Hoang et al. (2005).