Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome

OBJECTIVE: To present long-term respiratory function outcomes from an open-label, multi-center, phase 3 extension study (MOR-005) of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio A syndrome. METHODS: In part 1 of MOR-005, patients initially randomized to ERT in the 24-week pivotal study (MOR-004) remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two regimens. During part 2, all patients received elosulfase alfa 2.0 mg/kg/week. Respiratory function was one of the efficacy endpoints evaluated in MOR-005. Change from MOR-004 baseline to 120 weeks of treatment for the combined population was determined and compared with results from untreated patients from a Morquio A natural history study (MorCAP). RESULTS: Maximum voluntary ventilation (MVV) improved up to week 72 and then stabilized; forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) increased continuously over 120 weeks. Mean increases in the modified per-protocol population was 9.2 % for FVC, 8.8 % for FEV1, and 6.1 % for MVV after 120 weeks. All patients ≤14 years showed respiratory improvements, presumably in part related to growth; however, these were greater in treated patients. For those >14 years, treated patients showed improvements, while deterioration occurred in untreated. Altogether, the improvements were significantly greater (P < 0.05) in treated patients. CONCLUSIONS: Long-term ERT is associated with sustained improvements in respiratory function in Morquio A. In younger patients (≤14 years), some improvement may be ascribed to growth. In older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved

Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome

Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and -62.3 (1.8)% in the ITT and MPP populations, respectively. In the absence of a placebo group, significance of the sustained improvements could not be evaluated directly. However, to provide context for interpretation of results, comparisons were performed with untreated patients from a Morquio A natural history study. In contrast to the results of the extension study, the untreated patients experienced constant uKS levels and a gradual decline in endurance test results over a similar period of time. Differences from the untreated natural history study patients were significant for 6MWT, 3MSCT, and uKS outcomes for the cohort of patients receiving optimal dosing throughout the study and for all cohorts pooled together, for both ITT and MPP populations (P<0.05). Safety findings were consistent with those of the initial 24-week study, with no new safety signals identified

Heart rate variability (HRV) and muscular system activity (EMG) in cases of crash threat during simulated driving of a passenger car

Objectives: The aim of the study was to verify whether simultaneous responses from the muscular and circulatory system occur in the driver's body under simulated conditions of a crash threat. Materials and Methods: The study was carried out in a passenger car driving simulator. The crash was included in the driving test scenario developed in an urban setting. In the group of 22 young male subjects, two physiological signals - ECG and EMG were continuously recorded. The length of the RR interval in the ECG signal was assessed. A HRV analysis was performed in the time and frequency domains for 1-minute record segments at rest (seated position), during undisturbed driving as well as during and several minutes after the crash. For the left and right side muscles: m. trapezius (TR) and m. flexor digitorum superficialis (FDS), the EMG signal amplitude was determined. The percentage of maximal voluntary contraction (MVC) was compared during driving and during the crash. Results: As for the ECG signal, it was found that in most of the drivers changes occurred in the parameter values reflecting HRV in the time domain. Significant changes were noted in the mean length of RR intervals (mRR). As for the EMG signal, the changes in the amplitude concerned the signal recorded from the FDS muscle. The changes in ECG and EMG were simultaneous in half of the cases. Conclusion: Such parameters as mRR (ECG signal) and FDS-L amplitude (EMG signal) were the responses to accident risk. Under simulated conditions, responses from the circulatory and musculoskeletal systems are not always simultaneous. The results indicate that a more complete driver's response to a crash in road traffic is obtained based on parallel recording of two physiological signals (ECG and EMG)

Selected issuses of pedestrian safety on the roads in Poland

W artykule przedstawiono analizę bezpieczeństwa pieszych na polskich drogach w okresie ostatnich 10 lat. Dokonano przedstawienia liczby wypadków ogółem na polskich drogach i odniesiono ją do liczby zanotowanych wypadków z udziałem pieszych. Określono udział procentowy takich wypadków, który jak można zauważyć od kilku lat ma tendencję spadkową, a w roku 2014 osiągnął poziom 26%. Przeprowadzono analizę, gdzie mają miejsca wypadki z udziałem pieszych. Co warte zauważenia najczęściej występują one na przejściach dla pieszych i na skrzyżowaniach. W artykule dokonano zestawienia liczby zabitych pieszych. Przedstawiono ich udział w ogólnej liczbie zabitych na polskich drogach, w roku 2014 osiągnął on poziom 35%. Określono udział procentowy zabitych w zależności od miejsca powstania wypadku drogowego. Zauważono, że udział zabitych pieszych na skrzyżowaniach ustabilizował się na poziomie 15-18%, zaś na przejściach dla pieszych od roku 2011 niepokojąco rośnie i w roku 2014 osiągnął poziom blisko 25%.The article presents an analysis of pedestrian safety on Polish roads over the last 10 years. Were made to present the total number of accidents on Polish roads and reference it to the number of recorded accidents involving pedestrians. Determined percentage of such accidents, which as can be seen from a few years to decline, and in 2014 reached 26%.An analysis of where to place accidents involving pedestrians. What noteworthy frequently they occur at crossings and junctions. The article summarizes the number of pedestrians killed in recent years. They present their share in the total number killed on Polish roads, in 2014 it reached the level of 35%.The percentage killed was determined depending on the place of the accident. It was noted that the proportion of pedestrians killed at intersections stabilized at 15-18%, while at pedestrian crossings from 2011 alarmingly growing and in 2014 reached almost 25%

An analysis of collision avoidance manoeuvres in emergency traffic situations

This paper provides an overview of the research into the driver behaviour in simulated near collision situations. The aim of such investigations is to determine various parameters characterising the driver performance, e.g. driver response time. The driver response time is a very important parameter used, for example, to analyse road accidents. The results presented in this paper come from a study performed for two different emergency traffic situations using some predefined procedures (scenarios). The tests included situations in which a person driving a subject vehicle on a test track was to respond to obstacle mock-ups on a conflicting path (intrusion of a pedestrian from the left or from the right and intrusion of a vehicle from the right). The test data was used to determine the parameters describing the driver behaviour, i.e. the braking response time (braking manoeuvre), the steering response time (steering manoeuvre) and the intensity of the two manoeuvres. This paper compares the values of the driver response time for two scenarios, each with two variants. The average values of the braking response time and the steering response time were determined on a closed track in relation to the Time-To-Collision (TTC) in the range 0,6÷3s, characterising a near collision situation. Another parameter describing the driver behaviour discussed in this paper is the intensity of an avoidance manoeuvre. In the case of braking, the relative brake pedal displacement was analysed, while in the steering manoeuvre, the steering angle was taken into account. The average values of the braking displacement and the steering angle were presented in the function of the TTC. This paper looks at the relationship between the intensity of the driver response (braking, steering), the driver response time and the TTC

Traffic safety of main roads in Poland

The article presents an analysis of traffic safety on major communication routes in Poland. The total number of accidents in Poland has been compared and analysed in relation to the objectives in the context of the GAMBIT programs and the National Road Safety Program for the years 2013-2020. Analyses of the number of accidents in the years 2004-2017 have been presented in the article. A significant decrease in accidents has been demonstrated and annual changes determined, the value of which ranged from 12.15 to 6.74%. The statistics on fatalities have been also analysed. A midyear change in the number of fatalities has been determined, which constitute -4.4% in the analysed period. The data on the number of vehicles registered in Poland, which considerably affects traffic congestion, has been presented. In spite of this, there has been no increase in the number of accidents. The work compares changes in the length of the most important types of routes in Poland, as well as accidents and fatalities that occurred on them. With the decreasing overall number of accidents in Poland, there has been a noticeable drop in accidents per 100 km of road length also on these roads. The fatality rate per 100 accidents in Poland has been determined and the average value of this rate in 2017 was 8.64, while on the analysed roads it ranged from 12.3 to 14.6

Driver model for analyses precrashes situations - identification parameters model of driver basing on experimental research

W artykule zawarto główne założenia i krótką charakterystykę modelu kierowcy wykorzystywanego w badaniach sytuacji przedwypadkowych. Przedstawiono wyniki badań przeprowadzonych na torze samochodowym Kielce oraz w symulatorze AutoPW na Wydziale Transportu Politechniki Warszawskiej. Omówiono wyniki identyfikacji parametrów modelu matematycznego kierowcy. Wykazano, ze czas reakcji kierowców zależy od czasu ryzyka, podano także wykresy tych zależności. Porównano wyniki symulacji komputerowej zachowania kierowcy z wynikami zarejestrowanymi w badaniach eksperymentalnych.This article presents a short description of the model of a driver and model of a vehicle used in the research into pre-crash situations. Results of the research obtained on the racecourse Tor Kielce in Miedziana Góra and on AutoPW simulator have been given. In this paper the identification of parameters of the mathematical model of driver has been discussed. It is shown, that time of reaction of drivers de.pends on the risk time and graphs of these dependences are presented. The comparison of the results of driver behavior computer simulations with results registered in experimental research is given

Driver Model for the analysis of pre-accident situations - similarities and differences of results on a track and in a simulator

W artykule przedstawiono badania sytuacji przedwypadkowej, przeprowadzone na torze samochodowym oraz w symulatorze jazdy. Celem badań była weryfikacja poprawności opracowanego modelu kierowcy dla analizy tego typu sytuacji oraz identyfikacja jego parametrów. W artykule dokonano porównania parametrów charakteryzujących zachowanie kierowców w obu środowiskach badawczych. Ponieważ kierowca mógł wybierać rodzaj manewru obronnego - hamowanie lub (i) omijanie przeszkody, porównano częstość podejmowania obu tych manewrów, w każdym ze środowisk badawczych. Przeprowadzono porównanie czasu reakcji kierowców zarówno przy hamowaniu, jak i przy skręcie. Wyznaczono współczynniki korelacji między średnim czasem reakcji uzyskiwanym na torze i w symulatorze. Porównano również sposób realizacji manewrów (przebiegi opóźnienia i skrętu w funkcji czasu). Jako miarę liczbową sposobu realizacji manewrów przyjęto wartości parametrów matematycznego modelu kierowcy. Przeprowadzono analizę korelacyjną parametrów modelu na przykładzie wybranych kierowców.The article presents pre-accident simulation tests conducted on a car track and in a simulator. The aim of the tests was to verify the correctness of a driver model worked out for such a type of analysis and the identification of its parameters. The article shows the comparison of parameters characteristic for driver behaviour in both testing environments. As the driver may have chosen the manoeuvre to defend - to brake or (and) to avoid an obstacle, the frequency of choosing the above - mentioned manoeuvres has been compared in each testing environment. The comparison of driver reaction time was carried out during braking as well as turning. Correlation coefficients between average reaction time were determined. The comparison of a manoeuvre realization method has been conducted. As a numerical measure of the manoeuvre realization method, the parameters of a mathematical driver model were taken into account. The correlation analysis of model parameters was realized on the example of selected drivers

Czas reakcji w złożonej sytuacji drogowej (hamowanie podczas omijania przeszkody)

The way how vehicle drivers react to the road situations where the manoeuvres of braking and driving around an obstacle can be simultaneously carried out has been analysed. Three scenarios of simulated accident situations have been shown for which experiments were carried out on a motor vehicle testing track. Two scenarios were each played out with 100 drivers taking part in the tests and 30 drivers were subjected to tests according to the third scenario. For each of the scenarios, the drivers performed many tests characterized by different time-to-collision (TTC) values. The percentage distribution of specific drivers’ decisions about choosing a defensive manoeuvre (one or more) has been shown. For the action that was taken most often, where both the defensive manoeuvres, i.e. braking and driving around, were combined, the sequence of steps most frequently followed to avoid a collision has been presented. The driver’s reaction time values measured at braking and turning (to drive around an obstacle) have been given for the road situations under consideration. Both the average values obtained from the experiments and the quantiles shown in the graphs depend on the type of road situation and on the degree of risk, a measure of which is the TTC value.W pracy przeprowadzona została analiza sposobu reagowania kierowców w sytuacjach drogowych, w których dla uniknięcia wypadku możliwe jest jednoczesne podejmowanie zarówno manewru hamowania, jak i omijania. Pokazano trzy scenariusze symulowanych sytuacji wypadkowych, dla których przeprowadzono badania na torze samochodowym. W dwóch scenariuszach przebadano po stu kierowców, a w trzecim - trzydziestu. Dla każdego scenariusza badani kierowcy wykonywali wiele prób, scharakteryzowanych różnymi wartościami czasu do potencjalnego zderzenia z przeszkodą TTC (time to collision). Pokazano strukturę (udziały procentowe) podejmowanych przez kierowców decyzji o wyborze manewru (manewrów) obronnego. Dla najczęściej podejmowanego działania polegające na łączeniu obu manewrów obronnych - hamowania i omijania, pokazano najczęściej realizowaną sekwencję działań mających zapewnić uniknięcie zderzenia. W pracy podano uzyskane wartości czasu reakcji przy hamowaniu i przy skręcie (omijaniu) dla badanych sytuacji drogowych. Zarówno uzyskane wartości średnie jak i pokazane na wykresach kwantyle zależą od rodzaju sytuacji drogowej, jak i stopnia zagrożenia, którego miarą jest czas TT

Possibilities for improve of visibility the vehicle using a 360 degree system

W artykule przedstawiono problem związany z ograniczeniem pola widoczności tzw. stref martwych w pojazdach użytkowych oraz pojazdach ciężarowych. Problem związany z bezpieczeństwem użytkowania takich pojazdów wiąże się w dużej mierze ze specyfiką konstrukcji samego nadwozia pojazdu oraz miejsca pracy kierowcy. Jednym ze sposobów poprawy widoczności z miejsca kierowcy jest wprowadzanie różnych układów techniki wizyjnej oraz systemów przekształcania obrazu z wykorzystaniem w technice samochodowej mini kamer. Jednym z najnowszych rozwiązań w tym zakresie jest „system 360 stopni” analizujący w pełnym zakresie otoczenie wokół pojazdu. System ten może w znaczący sposób poprawić bezpieczeństwo manewrowania poprzez całkowitą likwidację stref martwych widoczności.The article presents the problem of limited field of view so. Blind spots in commercial vehicles and heavy goods vehicles. The problem of the safety of use of such vehicles is associated largely with the specifics of construction of the body of the vehicle and the driver's workplace. One way to improve visibility from the driver's seat is the introduction of different kinds of systems technology vision and image conversion system opened possibilities for use in automotive engineering mini-cameras. One of the latest solutions in this regard is the "system 360 degrees" fully analyzing the environment around the vehicle. This system can significantly improve the safety of maneuvering through the complete elimination of dead visibility