Population pharmacokinetics and dose rationale for aciclovir in term and pre-term neonates with herpes

Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of elimination, in renally-impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post-menstrual age (PMA) and creatinine clearance (CLCR) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one-compartment model with first-order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CLCR and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3-fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CLCR), suggesting different dosing requirement for pre-term neonates

Influence of screw combination and nail materials in the stability of anterograde reamed intramedullary nail in distal femoral fractures

Intramedullary nailing (IM) is a technique universally accepted to treat femoral diaphyseal fractures. The treatment of fractures located in the distal third remains a controversial issue though. A finite element model of the femur has been developed, analyzing distal fractures with several gap sizes combined with different interlocking combinations of distal screws with one oblique screw proximally to stabilize the intramedullary nail. The mechanical strength of the nail against bending and compression efforts was also studied. Beside the FE simulations, a clinical follow-up of 15 patients, 6 males and 9 females, with mean age of 53.2 years was carried out. Localizations of fractures were 10 in the right femur and 5 in the left femur, respectively. A fairly good correspondence agreement between clinical results and the simulated fractures in terms of gap size was found. Non-comminuted fractures had a mean consolidation time of 20.5 weeks (4.8 months), a tendency corresponding well to the mobility obtained in the FE simulations; Comminuted fractures on the other hand exhibited a higher mean consolidation period of 22.2 weeks (5.2 months) secondary to the excessive mobility at fracture site obtained by means of FE simulations. The best stability at fracture site was found for the system with three distal screws and the system with two distal screws placed medial lateral. The highest leverage of distal screws was obtained maximizing the distance between them and choosing the coronal plane for their orientation. The results obtained with both nail materials (stainless steel and titanium alloy) show a higher mobility when using titanium nails. Steel nails provide stiffer osteosyntheses than the titanium nails. In conclusion, the best screw combination in terms of stability to produce fracture healing and the least difficulties during treatment is the one which had one oblique proximal screw with two distal lateral screw implanted in the coronal plane

Influence of gap size, screw configuration, and nail materials in the stability of anterograde reamed intramedullary nail in femoral transverse fractures

Femoral shaft fractures are among the most severe injuries of the skeleton. They are associated with high morbidity and mortality. The most appropriate treatment depending on the type of fracture and location level should be chosen. A finite element model of the femur has been developed, analyzing various types of fractures in the subtrochanteric and diaphyseal supracondylar area, with several gap sizes, being stabilized with a single combination of screws for the intramedullary nail. The mechanical strength of the nail against bending and compression efforts was studied comparing two materials for the nail: stainless steel and titanium alloy. Beside the finite elements (FE) simulations, a clinical follow-up was carried out, considering a sample of 55 patients, 24 males, and 31 females, with mean age of 52.5 years. Localizations of fractures were 22 in the right femur and 33 in the left one, respectively. A good agreement between clinical results and the simulated fractures in terms of gap size was found. Non-comminuted fractures have a mean consolidation time of 4.1 months, which coincides with the appropriate mobility at fracture site obtained in the FE simulations, whereas comminuted fractures have a higher mean consolidation period estimated in 7.1 months, corresponding to the excessive mobility at fracture site obtained by means of FE simulations. The obtained results between both nail materials (stainless steel and titanium alloy) show a higher mobility when using titanium nails, which produce a higher rate of strains at the fracture site, amplitude of micromotions and bigger global movements compared to stainless-steel nails. Steel nails provide stiffer osteosyntheses than the titanium nails. In conclusion, anterograde locked nail is particularly useful in the treatment of a wide range of supracondylar fractures with proximal extension into the femoral diaphysis

Comparative analysis of the biomechanical behavior of anterograde/retrograde nailing in supracondylar femoral fractures

Supracondylar femoral fractures account for a noticeable percentage of the femoral shaft fractures, affecting two etiological groups: high energy trauma in young men, with good bone quality, and older women with osteoporotic femur. Surgical treatment of those kind of fractures remains controversial, with different surgical options such as plate and sliding barrel locking condylar plate, less invasive stabilization system (LISS) or intramedullary nailing, which has emerged as a new fixation choice in the treatment of that type of fractures. The present work performs a comparative study about the biomechanical behavior of anterograde and retrograde nailing in supracondylar femoral fractures type A, in order to determine the best choice of nailing and locking configuration. A three-dimensional finite element model of the femur was developed, modeling femoral supracondylar fracture and different nailing configurations, both for anterograde and retrograde nails. The study was focused on the immediately post-operative stage, verifying the appropriate stability of the osteosynthesis. The obtained results show a better biomechanical behavior for anterograde nails, providing a better stability from the point of view of global movements, lower stresses in screws, and less stress concentration in cortical bone. So, for the analyzed fractures and osteosyntheses types, anterograde nailing has demonstrated to be a better surgical option, being an excellent indication in supracondylar fractures of femur, with clear benefits compared to retrograde nailing, providing a better stabilization which enables for a more satisfactory fracture healing

Study of the polycarbonate-urethane/metal contact in different positions during gait cycle

Nowadays, a growing number of young andmore active patients receive hip replacement.More strenuous activities in such patients involve higher friction and wear rates, with friction on the bearing surface being crucial to ensure arthroplasty survival in the long term. Over the last years, the polycarbonate-urethane has offered a feasible alternative to conventional bearings. A finite element model of a healthy hip joint was developed and adjusted to three gait phases (heel strike, mid-stance, and toe-off), serving as a benchmark for the assessment of the results of joint replacement model. Three equivalent models were made with the polycarbonate-urethane Tribofit system implanted, one for each of the three gait phases, after reproducing a virtual surgery over the respective healthy models. Standard body-weight loads were considered: 230% body-weight toe-off, 275% body-weight mid-stance, and 350% body-weight heel strike. Contact pressures were obtained for the different models. When comparing the results corresponding to the healthy model to polycarbonate-urethane joint, contact areas are similar and so contact pressures are within a narrower value range. In conclusion, polycarbonate-urethane characteristics are similar to those of the joint cartilage. So, it is a favorable alternative to traditional bearing surfaces in total hip arthroplasty, especially in young patients

A methodology for the customized design of colonic stents based on a parametric model

The choice of necessary stent properties depends mainly on the length of the stenosis and degree of occlusion. So a stent design with variable radial stiffness along its longitudinal axis would be a good option. The design proposed corresponds to a tube-based stent with closed diamond-shaped cells made from a NiTi alloy. By acting independently on different geometric factors, variable geometries can be obtained with different radial force reactions. A design adjustment according to specific requirements, in order to get a better fit to ill-duct and reduces complications, is possible. A parametric analysis using finite element has been conducted to determine the influence of slot length, number of circumferential slots, tube thickness and shape-factor on stent mechanical behavior, which allow eliminating the need for extensive experimental work and knowing and quantifying the influence of those factors. The results of finite element simulations have been used, by means of least-squares fit techniques, to obtain analytical expressions for the main mechanical characteristics of the stent (Chronic Expansive Radial Force and Radial Compression Resistance) in terms of the different geometrical factors. This allows the stent geometry to be customized without launching an iterative and costly process of modeling and simulation for each case

A predictive mechanical model for evaluating vertebral fracture probability in lumbar spine under different osteoporotic drug therapies

Osteoporotic vertebral fractures represent a major cause of disability, loss of quality of life and even mortality among the elderly population. Decisions on drug therapy are based on the assessment of risk factors for fracture from bone mineral density (BMD) measurements.A previously developed model, based on the Damage and Fracture Mechanics, was applied for the evaluation of the mechanical magnitudes involved in the fracture process from clinical BMD measurements. BMD evolution in untreated patients and in patients with seven different treatments was analyzed from clinical studies in order to compare the variation in the risk of fracture. The predictive model was applied in a finite element simulation of the whole lumbar spine, obtaining detailed maps of damage and fracture probability, identifying high-risk local zones at vertebral body.For every vertebra, strontium ranelate exhibits the highest decrease, whereas minimum decrease is achieved with oral ibandronate. All the treatments manifest similar trends for every vertebra. Conversely, for the natural BMD evolution, as bone stiffness decreases, the mechanical damage and fracture probability show a significant increase (as it occurs in the natural history of BMD). Vertebral walls and external areas of vertebral end plates are the zones at greatest risk, in coincidence with the typical locations of osteoporotic fractures, characterized by a vertebral crushing due to the collapse of vertebral walls.This methodology could be applied for an individual patient, in order to obtain the trends corresponding to different treatments, in identifying at-risk individuals in early stages of osteoporosis and might be helpful for treatment decisions

Cementless hydroxyapatite coated hip prostheses

More than twenty years ago, hydroxyapatite (HA), calcium phosphate ceramics, was introduced as a coating for cementless hip prostheses. The choice of this ceramic is due to its composition being similar to organic apatite bone crystals. This ceramic is biocompatible, bioactive, and osteoconductive. These qualities facilitate the primary stability and osseointegration of implants Our surgical experience includes the implantation of more than 4,000 cementless hydroxyapatite coated hip prostheses since 1990 The models implanted are coated with HA in the acetabulum and in the metaphyseal area of the stem.The results corresponding to survival and stability of implants were very satisfactory in the long-term. From our experience, HA-coated hip implants are a reliable alternative which can achieve long termsurvival, provided that certain requirements aremet: good design selection, sound choice of bearing surfaces based on patient life expectancy,meticulous surgical technique, and indications based on adequate bone quality

Fostering voluntourism satisfaction and future behaviour in island destinations

Indexación ScopusVolunteer tourism, which is commonly referred to as voluntourism, is currently a dynamic alternative travel option with a focus on sustainable tourism. However, existing literature reveals that voluntourism activities do not meet tourists’ expectation, fail to provide experiences related to environmental issues, and thus, leads to their dissatisfaction. Realising the importance of the satisfaction of the voluntourists’ future behaviour, applying the volunteer function inventory, coupled with environmental concern, the authors aim to identify factors influencing voluntourists’ satisfaction and present the outcomes of voluntourists’ satisfaction among island visitors in Malaysia. Using a purposive sampling method, the data were collected through a survey among voluntarists in east coast island tourist destinations. A total of 278 valid questionnaires were gathered from two sessions of data collection process. Due to the model’s complexity, SEM-PLS version 3.3.2. was employed to analyse the hypotheses of the study. The results of the study revealed that career and social functions, in contrast with other variables, do not positively influence the voluntourists’ satisfaction. The continuous intention and the intention to recommend factors positively support the research model. Studies on voluntourists in Malaysian island destinations are relatively novel. Besides enriching the literature on voluntourism, which is particularly scarce especially in the Asian setting, the findings are also beneficial to local governments and voluntourism organisations to develop suitable approaches and policies to promote voluntourism in island destinations. The study is limited to the island destination setting. Future studies should focus on other destinations such as cultural and heritage sites, because these destinations have sentimental values that should be preserved. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.https://www.mdpi.com/2071-1050/13/5/276