Biomechanical effect of the configuration of screw hole style on locking plate fixation in proximal humerus fracture with a simulated gap: A finite element analysis

BackgroundLocking plate fixation for proximal humeral fractures is a commonly used device. Recently, plate breakages were continuously reported that the implants all have a mixture of holes allowing placement of both locking and non-locking screws (so-called combi plates). In commercialized proximal humeral plates, there still are two screw hole styles included “locking and dynamic holes separated” and “locking hole only” configurations. It is important to understand the biomechanical effect of different screw hole style on the stress distribution in bone plate.MethodsFinite element method was employed to conduct a computational investigation. Three proximal humeral plate models with different screw hole configurations were reconstructed depended upon an identical commercialized implant. A three-dimensional model of a humerus was created using process of thresholding based on the grayscale values of the CT scanning of an intact humerus. A “virtual” subcapital osteotomy was performed. Simulations were performed under an increasing axial load. The von Mises stresses around the screw holes of the plate shaft, the construct stiffness and the directional displacement within the fracture gap were calculated for comparison.ResultsThe mean value of the peak von Mises stresses around the screw holes in the plate shaft was the highest for combi hole design while it was smallest for the locking and dynamic holes separated design. The stiffness of the plate-bone construct was 15% higher in the locking screw only design (132.6 N/mm) compared with the combi design (115.0 N/mm), and it was 4% higher than the combi design for the locking and dynamic holes separated design (119.5 N/mm). The displacement within the fracture gap was greatest in the combi hole design, whereas it was smallest for the locking hole only design.ConclusionsThe computed results provide a possible explanation for the breakages of combi plates revealed in clinical reports. The locking and dynamic holes separated design may be a better configuration to reduce the risk of plate fracture.     

Experimental study of the influence of the counter and scintillator on the universal curves in the cross-efficiency method in LSC

The cross-efficiency method in LSC is one of the approaches proposed for the extension of the Système International de Référence (SIR) to radionuclides emitting no gamma radiation. This method is based on a so-called “universal cross-efficiency curve”, establishing a relationship between the detection efficiency of the radionuclide to be measured and the detection efficiency of a suitable tracer. This paper reports a study at LNHB on the influence of the scintillator and of the LS counter on the cross-efficiency curves. This was done by measuring the cross-efficiency curves obtained for ⁶³Ni and ⁵⁵Fe vs. ³H, using three different commercial LS counters (Guardian 1414, Tricarb 3170 and Quantulus 1220), three different liquid scintillator cocktails (Ultima Gold, Hionic Fluor and PicoFluor 15 from Perkin Elmer^®), and for chemical and colour-quenched sources. This study shows that these cross-efficiency curves are dependent on the scintillator, on the counter used and on the nature of the quenching phenomenon, and thus cannot definitively be considered as “universal”.     

Innovation in Chemistry,Manufacturing, and Controls—A Regulatory Perspective From Industry

This review describes the landscape of novel modalities such as cell and gene therapies, viruses, other novel biologics, oligomers, and emerging technologies, including modern analytics. We summarize the regulatory history and recent landmark developments in some major markets and examine specific chemistry, manufacturing, and controls (CMC) challenges, including suggestions for exploration of potential science-based approaches in support of regulatory strategy development from an industry perspective. In addition, we evaluate the economic factors contributing to patient access to innovation and discuss the impact of regulation. There is a desperate need for a consistent form of regulation where global approaches to regulatory strategies can be harmonized, and specific CMC challenges can be dealt with using the appropriate science and risk-based tools. Although these tools are well described in current guidance documents, the specifics of applicability to complex novel modalities can still result in differing regulatory advice and outcomes. The future goals for efficiently regulating innovative modalities and technologies could be aided by more regulatory harmonization, regulatory education, and industry cooperation through consortia, enabling industry to supply key information to regulators in a transparent yet well-defined manner, and utilizing mutually understood risk-benefit analyses to produce drugs with appropriate safety, efficacy, and quality characteristics.     

The potential of an automated system to identify the upper limb component of a controlled sitting posture

Full trunk control in sitting is demonstrated only when the head-trunk are aligned and upper limbs remain free of contact from mechanical support. These components represent a Controlled Kinetic Chain and can be evaluated in people with neuromotor disability using the Segmental Assessment of Trunk Control (SATCo) when a therapist provides manual trunk support at different segmental levels. However, the SATCo, as with other clinical assessments of control, is subjective. The SATCo was translated to objective rules relating the position of the hands and elbows to the head-trunk and then tested to determine the extent to which this automated objective method replicated the clinical judgement.Clinical evaluation used video to determine whether the upper limb was free of mechanical support while the objective evaluation used 3D motion capture of the trunk and upper limbs with a classification rule. The agreement between clinical and objective classification was calculated for three conditions of a distance-from-support-surface threshold parameter in five healthy adults and five children with cerebral palsy.The unfitted (zero-threshold values) method replicated the clinical judgement in part (68.26% ± 15.7, adults, 48.3% ± 33.9 children). The fitted (level-of-support determined) agreement showed that the process could be refined using trial specific parameters (88.32% ± 5.3 adults, 89.84% ± 10.2 children). The fixed-values agreement showed high values when using general group parameters (80.80% ± 3.1 adults, 74.31% ± 21.5 children).This objective classification of the upper limb component of trunk control largely captures the clinical evaluation. It provides the first stages in development of a clinically-friendly fully automated method.     

Association between underweight and taste sensitivity in middle‐ to old‐aged nursing home residents in Sri Lanka: a cross‐sectional study

Low taste sensitivity may be one factor related to undernutrition, which is a major problem in developing countries. The purpose of this cross‐sectional study was to examine the association between underweight, one indicator of undernutrition, and taste sensitivity in middle‐ to old‐aged Sri Lankan nursing home residents. Participants were 946 residents with BMI of <25·0 from 25 nursing homes. Data were obtained on height, weight, taste sensitivity, subjective taste ability, sex, age, ethnicity, number of years in nursing homes, activities of daily living (ADL), frequency of exercise, bowel movements, smoking status, drinking status, current number of chronic diseases, number and kinds of medications used, self‐reporting questionnaire 20 (SRQ20), subjective smell ability, number of teeth present, Eichner index and flow rate of saliva. Low sensitivity to bitter taste, being male, old age, low ADL, smoking experience, drinking experience, fewer medications used and no use of medication for hypertension and diabetes were each associated with underweight (P < 0·05). In a multilevel Poisson regression model adjusted for sex, age, ADL, smoking status, drinking status, number of medications used, use of medication for hypertension and diabetes and flow rate of saliva, subjects with low sensitivity (>0·003% quinine hydrochloride dihydrate) to bitter taste had a significant 1·70 times higher prevalence ratio (95% confident interval 1·04–2·80) for underweight compared with those with high sensitivity (0·0001% quinine hydrochloride dihydrate). These results suggest that low taste sensitivity to bitter taste may be one factor related to underweight.     

Finite element analysis of stress distribution in anchor teeth in surgically assisted rapid palatal expansion

The treatment of a transverse maxillary deficiency in skeletally mature individuals should include surgically assisted rapid palatal expansion. This study evaluated the distribution of stresses that affect the expander's anchor teeth using finite element analysis when the osteotomy is varied. Five virtual models were built and the surgically assisted rapid palatal expansion was simulated. Results showed tension on the lingual face of the teeth and alveolar bone, and compression on the buccal side of the alveolar bone. The subtotal Le Fort I osteotomy combined with intermaxillary suture osteotomy seemed to reduce the dissipation of tensions. Therefore, subtotal Le Fort I osteotomy without a step in the zygomaticomaxillary buttress, combined with intermaxillary suture osteotomy and pterygomaxillary disjunction may be the osteotomy of choice to reduce tensions on anchor teeth, which tend to move mesiobuccally (premolar) and distobuccally (molar).     

A Review of: “ Handbook of Adaptive Designs in Pharmaceutical and Clinical Development,by A. Pong and S.-C. Chow (Eds.)”

In practice, there exist many disease processes with three ordinal disease classes; for example, in the detection of Alzheimer’s disease (AD) a patient can be classified as healthy (disease-free stage), mild cognitive impairment (early disease stage), or AD (full disease stage). The treatment interventions and effectiveness of such disease processes will depend on the disease stage. Therefore, it is important to develop diagnostic tests with the ability to discriminate between the three disease stages. Measuring the overall ability of diagnostic tests to discriminate between the three classes has been discussed extensively in the literature. However, there has been little proposed on how to select clinically meaningful thresholds for such diagnostic tests, except for a method based on the generalized Youden index by Nakas et al. (2010). In this article, we propose two new criteria for selecting diagnostic thresholds in the three-class setting. The numerical study demonstrated that the proposed methods may provide thresholds with less variability and more balance among the correct classification rates for the three stages. The proposed methods are applied to two real examples: the clinical diagnosis of AD from the Washington University Alzheimer’s Disease Research Center and the detection of liver cancer (LC) using protein segments.     

Inference for Clinical Trials with Some Protocol Amendments

ABSTRACT

The use of adaptive methods in clinical development has become very popular in recent years due to its flexibility in modifying trial procedures and/or statistical procedures of on-going clinical trials. Modifications to trial procedures are usually documented by protocol amendments. However, the actual patient population after protocol amendments could deviate from the originally targeted patient population. In addition, protocol amendments made based on accrued data of the on-going trial may distort the sampling distribution of the statistic designed for the case of no protocol change. In this article, we model the population deviations due to protocol amendments using some covariates and study how to develop a valid statistical inference procedure. An example concerning an asthma trial is presented for illustration.