A fully automatic tool for development of population pharmacokinetic models.

Population pharmacokinetic (PK) models are widely used to inform drug development by pharmaceutical companies and facilitate drug evaluation by regulatory agencies. Developing a population PK model is a multi-step, challenging, and time-consuming process involving iterative manual model fitting and evaluation. A tool for fully automatic model development (AMD) of common population PK models is presented here.

Simulation-based evaluation of the Pharmpy Automatic Model Development tool for population pharmacokinetic modeling in early clinical drug development.

The Pharmpy Automatic Model Development (AMD) tool automates the building of population pharmacokinetic (popPK) models by utilizing a systematic stepwise process. In this study, the performance of the AMD tool was assessed using simulated datasets. Ten true models mimicking classical popPK models were created.

Gait Characteristics over the Six-minute Walk Test in Older Women of a Specific Portuguese Community: A Cross-Sectional Study.

Introduction And Objective: There is limited research on the changes that can occur in the gait biomechanical parameters of older adults over long-distance walking. Thus, this study aimed to evaluate the gait characteristics of older women of a specific Portuguese community over the six-minute walk test (6MWT) along with gait spatial and temporal parameters and angular kinematics of the lower limb joints.

Materials And Methods: Twenty-six older women voluntarily participated.

Deep squat test - Functional movement Screen: Convergent validity and ability to discriminate subjects with different levels of joint mobility.

Background: Functional Movement Screen (FMS) is an important tool in the assessment of exercise practice. Assuming FMS lacks precise validity for assessing postural deficits, further research is needed to assess whether it is a sufficiently precise tool for analysing joint mobility. Research aims were to evaluate: convergent validity of Deep Squat (DS) - one of FMS tests - regarding joint mobility, using data from a three-dimensional motion analysis as a comparable method; DS's ability to discriminate between subjects with different joint mobility levels.

Proprioceptive and Strength Exercise Guidelines to Prevent Falls in the Elderly Related to Biomechanical Movement Characteristics.

Falls are a major concern in the elderly and walking is an important daily activity in which falls occur, with tripping and slipping being the most frequent causes. Gait biomechanical parameters have been related to the occurrence of falls in the elderly. Moreover, there is evidence that falls can be prevented through exercise programs, which have been shown to be also effective in improving gait biomechanical parameters.

Valorisation of Recycled Cement Paste: Feasibility of a Short-Duration Carbonation Process.

Cement paste powder (CPP) is a by-product of the recycling process of concrete with an elevated carbonation capability and potential to be recycled as a binding material in new concrete batches. The application of a carbonation treatment to CPP improves this potential even more, besides the evident gains in terms of CO net balance. However, the long duration usually adopted in this treatment, from 3 to 28 days, hampers the industrial viability of the process.

Biomechanical Performance Factors in the Track and Field Sprint Start: A Systematic Review.

In athletics sprint events, the block start performance can be fundamental to the outcome of a race. This Systematic Review aims to identify biomechanical factors of critical importance to the block start and subsequent first two steps performance. A systematic search of relevant English-language articles was performed on three scientific databases (PubMed, SPORTDiscus, and Web of Science) to identify peer-reviewed articles published until June 2021.

Fractal Brownian Motion Assessment of the Center of Pressure Excursion During Impulse Phase on Standard Vertical Jump.

This study presents and applies fractal Brownian motion assessment of the center of pressure (COP) excursion during feet ground contact on standard vertical jump impulse phase with long and short countermovement (CM) in relation with lower limb muscle stretch-shortening cycle (SSC) comparing it with no CM and SSC. Fifty-four tests were performed by a group of six healthy male students of sports and physical education degree without previous injury, specific training, or fitness ability. Three repetitions were performed by each subject of a squat jump (SJ) without CM and SSC, countermovement jump (CMJ) with long CM and SSC, as well as drop jump (DJ) with short CM and SSC after depth jump from a 40 cm step.

Equine Rehabilitation: A Scoping Review of the Literature.

Injuries to the locomotor system are a common problem in athletic horses. Veterinarians address these injuries using appropriate medical, surgical, and pharmacological treatments. During or after recovery from the initial injury, horses may be treated for functional locomotor deficits using specific rehabilitation techniques aimed at restoring full athletic performance.

Immediate effect of individual bars of insoles and their combination on gait parameters in asymptomatic healthy adults.

: The way how individual bars of sensorimotor insoles influence the gait kinematics is not fully understood yet. Therefore, this study aimed to explore the effect of three sensorimotor orthotic conditions (the medial calcaneal and retrocapital lateral bars and their combination) on the gait parameters in healthy adults during the stance phase of gait cycle.: Twenty-six young adults performed 20 gait cycles in each condition using their self-selected cadence and provided standardised shoes with the base-sole and the three types of orthotics.

Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII.

Bayesian forecasting for dose individualization of prophylactic factor VIII replacement therapy using pharmacokinetic samples is challenged by large interindividual variability in the bleeding risk. A pharmacokinetic-repeated time-to-event model-based forecasting approach was developed to contrast the ability to predict the future occurrence of bleeds based on individual (i) pharmacokinetic, (ii) bleeding, and (iii) pharmacokinetic, bleeding and covariate information using observed data from the Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease (LEOPOLD) clinical trials (172 severe hemophilia A patients taking prophylactic treatment). The predictive performance assessed by the area under receiver operating characteristic (ROC) curves was 0.

Relationship between factor VIII activity, bleeds and individual characteristics in severe hemophilia A patients.

Pharmacokinetic-based prophylaxis of replacement factor VIII (FVIII) products has been encouraged in recent years, but the relationship between exposure (factor VIII activity) and response (bleeding frequency) remains unclear. The aim of this study was to characterize the relationship between FVIII dose, plasma FVIII activity, and bleeding patterns and individual characteristics in severe hemophilia A patients. Pooled pharmacokinetic and bleeding data during prophylactic treatment with BAY 81-8973 (octocog alfa) were obtained from the three LEOPOLD trials.

Postpartum ovarian vein thrombosis and venous anatomical variation.

A 34-year-old multipara presented 72 hours postpartum with acute right-sided abdominal pain. The investigation revealed mild leucocytosis with positive D-dimer and elevated C reactive protein. Abdominal ultrasound and abdominopelvic CT demonstrated an enlarged right ovarian vein with endoluminal thrombus, representing postpartum ovarian vein thrombosis.

Handling interoccasion variability in model-based dose individualization using therapeutic drug monitoring data.

Aims: This study aims to assess approaches to handle interoccasion variability (IOV) in a model-based therapeutic drug monitoring (TDM) context, using a population pharmacokinetic model of coagulation factor VIII as example.

Methods: We assessed 5 model-based TDM approaches: empirical Bayes estimates (EBEs) from a model including IOV, with individualized doses calculated based on individual parameters either (i) including or (ii) excluding variability related to IOV; and EBEs from a model excluding IOV by (iii) setting IOV to zero, (iv) summing variances of interindividual variability (IIV) and IOV into a single IIV term, or (v) re-estimating the model without IOV. The impact of varying IOV magnitudes (0-50%) and number of occasions/observations was explored.

Generalized Lower Limb Joint Angular Phase Space Analysis of Subject Specific Normal and Modified Gait.

This study presents and applies generalized angular phase space analysis to lower limb joint angles of specific subject during normal and modified gait for discrimination of gait and joint angular movements. Case study of an adult healthy male in-vivo and noninvasive kinematic assessment of skin surface adhesive markers at lower limb was performed at human movement lab during normal gait, stiff knee gait and slow running. Musculoskeletal modeling was performed using AnyGait v.

Novel sintering-free scaffolds obtained by additive manufacturing for concurrent bone regeneration and drug delivery: Proof of concept.

Advances on the fabrication of sintering-free biphasic calcium phosphate (BCP)/natural polymer composite scaffolds using robocasting as additive manufacturing technique are presented in the present work. Inks with high amounts of BCP powders (45 vol%) containing different HA/β-TCP ratios, in presence of crosslinked polymer, were successfully fine-tuned for extrusion by robocasting. The non-existence of sintering step opened the possibility to obtain drug loaded scaffolds by adding levofloxacin to the extrudable inks.

Differences in foot contact times between obese and non-obese postmenopausal women when crossing obstacles.

Objective: This study aimed to investigate the foot contact time differences between obese and non-obese subjects during walking when crossing obstacles.

Methods: Ninety-eight postmenopausal women were assigned to four groups, and their plantar pressure temporal data were collected using a two-step protocol during walking when crossing an obstacle set at 30% height of lower limb length of each subject. The initial, final, and duration of contact of 10 foot areas were measured.

Chemoembolization of Hepatocellular Carcinoma with Drug-Eluting Polyethylene Glycol Embolic Agents: Single-Center Retrospective Analysis in 302 Patients.

Purpose: To evaluate the efficacy and safety of transarterial chemoembolization with polyethylene glycol (PEG) drug-eluting embolic agents in the treatment of hepatocellular carcinoma (HCC).

Materials And Methods: A single-center retrospective study of 302 patients (258 men; 85.4%) with HCC treated during a 20-month period was conducted.

Dynamic joint stiffness of the ankle in healthy and rheumatoid arthritis post-menopausal women.

The purpose of this study was to compare rheumatoid arthritis post-menopausal women (RAPW) with pathological involvement of the lower limb joints and age-matched healthy post-menopausal women (AHPW) in regard to the dynamic joint stiffness of the ankle (DJS) during the stance phase of gait. Data were collected from 18 RAPW and 18 AHPW. Gait was assessed by a three-dimensional motion analysis system synchronised with a force plate.

The Effects of Nordic Walking and Slope of the Ground on Lower Limb Muscle Activity.

Psurny, M, Svoboda, Z, Janura, M, Kubonova, E, Bizovska, L, Martinez Lemos, RI, and Abrantes, J. The effects of Nordic walking and slope of the ground on lower limb muscle activity. J Strength Cond Res 32(1): 217-222, 2018-Nordic walking (NW) has proven to be a simple and safe mode of exercise that can be used in various types of sport, recreation, and rehabilitation activities.

Consistency of surface electromyography assessment at lower limb selected muscles during vertical countermovement.

Given the difficulty of invasive methods to assess muscle action during natural human movement, surface electromyography (sEMG) has been increasingly used to capture muscle activity in relation to kinesiological analysis of specific tasks. Isolated isometric, concentric and eccentric forms of muscle action have been receiving the most attention for research purposes. Nevertheless natural muscle action frequently involves the use of a preceding eccentric muscle action as a form of potentiation of immediate muscle concentric action, in what is designated as muscle stretch-shortening cycle (SSC).

Foot Rollover Temporal Parameters During Walking Straight Ahead and Stepping Over Obstacles: Obese and Non-Obese Postmenopausal Women.

The aim of this study was to compare the temporal foot rollover data between walking straight ahead and stepping over obstacles for obese and non-obese postmenopausal women. Plantar pressure data were collected from 67 women. The initial, final, and duration of contact of 10 foot areas were measured.

A Prospective Population Pharmacokinetic Study on Morphine Metabolism in Cancer Patients.

Background: Oral and subcutaneous morphine is widely used for the treatment of cancer-related pain; however, solid pharmacokinetic data on this practice are lacking. Furthermore, it is largely unknown which factors contribute to the variability in clearances of morphine and its metabolites and whether morphine clearance is related to treatment outcome.

Methods: Blood samples from 49 cancer patients treated with oral and/or subcutaneous morphine were prospectively collected and were used to develop a population pharmacokinetic model for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G).