A Novel Method for Stratification of Major Complication Risk Using Body Mass Index Thresholds for Patients Undergoing Total Hip Arthroplasty: A National Cohort of 224,413 Patients

IntroductionElevated body mass index (BMI) is associated with complications following Total Hip Arthroplasty (THA). Since obese individuals are almost 10 times more likely to require THA compared to non-obese individuals, we need to understand the risk-benefit continuum while considering THA in obese patients. We aimed to determine data-driven thresholds for BMI at which the risk of major complications following THA increases significantly.MethodsPatients were identified in a national database who underwent primary THA from 2010 to 2020. BMI thresholds were identified using the stratum-specific likelihood ratio (SSLR) methodology, which is an adaptive technique that allows for identification of BMI cut-offs, at which the risk of major complications is increased significantly . BMI cutoffs identified using SSLR were used to create a logistic regression model.ResultsA total of 224,413 patients were identified with a mean age of 66 ± 10, BMI 32 ± 6.7, and 7,186 (3%) sustained a major complication. BMI thresholds were defined as 19-31, 32-37, 38-49 and 50+. Overall, the absolute risk of major complications increased from 2.9% in the lowest BMI strata to 7.5% in the highest BMI strata. Compared to patients with a BMI between 19-31, the odds of sustaining a major complication sequentially increased by 1.2, 1.6, and 2.5-times for patients in each higher BMI strata (all, P < .05).ConclusionsWe have identified BMI cutoffs using SSLR that categorizes patients into four categories of risk for major complications in a nationally representative patient sample. These thresholds can be used in the surgical decision-making process between patients and surgeons.     

Optimal control analysis of a tuberculosis model with exogenous re-infection and incomplete treatment

A new mathematical model of tuberculosis (TB) featuring exogenous re-infection and incomplete treatment is presented and analyzed. The model divides total population into susceptible, latently infected, actively infected (uninformed and enlightened), and treatment classes. The model with or without incomplete treatment exhibits backward bifurcation phenomenon, which is caused by the presence of exogenous re-infection. However, further investigation reveals that the absence of incomplete treatment has the potential to reduce the backward bifurcation range significantly. The global dynamics of the TB model without exogenous re-infection is completely determined by the basic reproduction number under certain modifications on parameters. Furthermore, the model is extended to include three time-dependent control functions, such as public awareness campaign, treatment effort, and preventive control against incomplete treatment. The existence of the optimal control for the nonautonomous model is proven and the three controls are characterized using Pontryagin's maximum principle. Numerical simulations are performed to show the significance of singular implementation of each of the controls and combination of the three controls in minimizing the TB burden in the population.     

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals

A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000 mg/kg). The data on flumioxazin concentration in pregnant rats (30 mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model. Liver microsomes of female rats and a mixed gender of humans were used for the in vitro metabolism study. To determine the % of flumioxazin absorbed after administration at a dose of 1000 mg/kg assuming maximum accidental intake, the biliary excretion study of [phenyl-U-¹⁴C]flumioxazin was conducted in bile duct-cannulated female rats (Crl:CD (SD)) to collect and analyze the bile, urine, feces, gastrointestinal tract, and residual carcass. The % of flumioxazin absorbed at a dose of 1000 mg/kg in rats was low (12.3%) by summing up ¹⁴C of the urine, bile, and residual carcass. The pregnant human model that was developed demonstrated that the maximum flumioxazin concentration in the blood and fetus of a pregnant human at a dose of 1000 mg/kg po was 0.86 μg/mL and 0.68 μg/mL, respectively, which is much lower than K_m (202.4 μg/mL). Because the metabolism was not saturated and the absorption rate was low at a dose of 1000 mg/kg, the calculated flumioxazin concentration in pregnant humans was thought to be relatively low, considering the flumioxazin concentration in pregnant rats at a dose of 30 mg/kg. For the safety assessment of flumioxazin, these results would be useful for further in vitro toxicology experiments.     

Characterization of Open-Cell Sponges via Magnetic Resonance and X-ray Tomography

The applications of polymeric sponges are varied, ranging from cleaning and filtration to medical applications. The specific properties of polymeric foams, such as pore size and connectivity, are dependent on their constituent materials and production methods. Nuclear magnetic resonance imaging (MRI) and X-ray micro-computed tomography (µCT) offer complementary information about the structure and properties of porous media. In this study, we employed MRI, in combination with µCT, to characterize the structure of polymeric open-cell foam, and to determine how it changes upon compression, µCT was used to identify the morphology of the pores within sponge plugs, extracted from polyurethane open-cell sponges. MRI T₂ relaxation maps and bulk T₂ relaxation times measurements were performed for 7° dH water contained within the same polyurethane foams used for µCT. Magnetic resonance and µCT measurements were conducted on both uncompressed and 60% compressed sponge plugs. Compression was achieved using a graduated sample holder with plunger. A relationship between the average T₂ relaxation time and maximum opening was observed, where smaller maximum openings were found to have a shorter T₂ relaxation times. It was also found that upon compression, the average maximum opening of pores decreased. Average pore size ranges of 375–632 ± 1 µm, for uncompressed plugs, and 301–473 ± 1 µm, for compressed plugs, were observed. By determining maximum opening values and T₂ relaxation times, it was observed that the pore structure varies between sponges within the same production batch, as well as even with a single sponge.     

Biological Safety Evaluation and Surface Modification of Biocompatible Ti–15Zr–4Nb Alloy

We performed biological safety evaluation tests of three Ti–Zr alloys under accelerated extraction condition. We also conducted histopathological analysis of long-term implantation of pure V, Al, Ni, Zr, Nb, and Ta metals as well as Ni–Ti and high-V-containing Ti–15V–3Al–3Sn alloys in rats. The effect of the dental implant (screw) shape on morphometrical parameters was investigated using rabbits. Moreover, we examined the maximum pullout properties of grit-blasted Ti–Zr alloys after their implantation in rabbits. The biological safety evaluation tests of three Ti–Zr alloys (Ti–15Zr–4Nb, Ti–15Zr–4Nb–1Ta, and Ti–15Zr–4Nb–4Ta) showed no adverse (negative) effects of either normal or accelerated extraction. No bone was formed around the pure V and Ni implants. The Al, Zr, Nb, and Ni–Ti implants were surrounded by new bone. The new bone formed around Ti–Ni and high-V-containing Ti alloys tended to be thinner than that formed around Ti–Zr and Ti–6Al–4V alloys. The rate of bone formation on the threaded portion in the Ti–15Zr–4Nb–4Ta dental implant was the same as that on a smooth surface. The maximum pullout loads of the grit- and shot-blasted Ti–Zr alloys increased linearly with implantation period in rabbits. The pullout load of grit-blasted Ti–Zr alloy rods was higher than that of shot-blasted ones. The surface roughness (Ra) and area ratio of residual Al₂O₃ particles of the Ti–15Zr–4Nb alloy surface grit-blasted with Al₂O₃ particles were the same as those of the grit-blasted Alloclassic stem surface. It was clarified that the grit-blasted Ti–15Zr–4Nb alloy could be used for artificial hip joint stems.     

Peak Cough Flow Fails to Detect Upper Airway Collapse During Negative Pressure Titration for Cough-Assist

ObjectiveTo study the ability of peak cough flow (PCF) and effective cough volume, defined as the volume exsufflated >3 L/s, to detect upper airway collapse during mechanical insufflation-exsufflation (MI-E) titration in neuromuscular patients.DesignProspective observational study.SettingRehabilitation hospital.ParticipantsPatients (N=27) with neuromuscular disease causing significant impairment of chest wall and/or diaphragmatic movement.InterventionsThe lowest insufflation pressure producing the highest inspiratory capacity was used. Exsufflation pressure was decreased from ?20 cm H₂O to ?60/?70 cm H₂O, in 10-cm H₂O decrements, until upper airway collapse was detected using the reference standard of flow-volume curve analysis (after PCF, abrupt flattening or flow decrease vs previous less negative exsufflation pressure).Main Outcome MeasuresPCF and effective cough volume profiles during expiration with MI-E.ResultsUpper airway collapse occurred in 10 patients during titration. Effective cough volume increased with decreasing expiratory pressure then decreased upon upper airway collapse occurrence. PCF continued to increase after upper airway collapse occurrence. In 5 other patients, upper airway collapse occurred at the initial ?20 cm H₂O exsufflation pressure, and during titration, PCF increased and effective cough volume remained unchanged at <200 mL. PCF had 0% sensitivity for upper airway collapse, whereas effective cough volume had 100% sensitivity and specificity.ConclusionOf 27 patients, 15 experienced upper airway collapse during MI-E titration. Upper airway collapse was associated with an effective cough volume decrease or plateau and with increasing PCF. Accordingly, effective cough volume, but not PCF, can detect upper airway collapse.     

Accuracy of objective tests for diagnosing adult asthma in symptomatic patients: A systematic literature review and hierarchical Bayesian latent-class meta-analysis

BackgroundWe obtain summary estimates of the accuracy of additional objective tests for the diagnosis of adult asthma using systematic review and meta-analysis of diagnostic test accuracy studies.MethodsMedline, Embase, and other relevant electronic databases were searched for papers published between January 1989 and December 2016. Studies were included if they evaluated the diagnostic accuracy of objective tests, including airway reversibility (AR), airway hyperresponsiveness (AHR), and fractionated exhaled nitric oxide (FeNO) for the diagnosis of adult asthma in patients with symptoms suggestive of asthma. If papers were assessed appropriate using the adapted QUADAS-2 tool, meta-analysis was conducted using the hierarchical bivariate model. This hierarchical model accounts for both within and between study variability.ResultsSixteen studies reported the performance of the evaluated objective tests at presentation. For diagnosis of adult asthma, overall sensitivity and specificity for AR were 0.39 (95% confidence interval [CI] 0.18 to 0.66) and 0.95 (95% CI 0.86 to 1.00); for AHR, 0.86 (95% CI 0.61 to 1.00) and 0.95 (95% CI 0.77 to 1.00); for FeNO, 0.65 (95% CI 0.53 to 0.77) and 0.83 (95% CI 0.75 to 0.90). Comprehensive comparison of three diagnostic tools for adult asthma using the back-calculated likelihood rate (LR) showed that AR and AHR corresponded to a higher LR+, and AHR gave a lower LR-.ConclusionsIn the current situation of no gold standard for diagnosis of adult asthma, AR and AHR are appropriate for ruling-in the true diagnosis, and AHR is superior for ruling-out a diagnosis. Since each objective test had a specific characteristic, it should be chosen depending on the situation, such as the capacity of the institution and the conditions of patients.     

Modeling the site-specific variation of selection patterns along lineages

The unambiguous footprint of positive Darwinian selection in protein-coding DNA sequences is revealed by an excess of nonsynonymous substitutions over synonymous substitutions compared with the neutral expectation. Methods for analyzing the patterns of nonsynonymous and synonymous substitutions usually rely on stochastic models in which the selection regime may vary across the sequence but remains constant across lineages for any amino acid position. Despite some work that has relaxed the constraint that selection patterns remain constant over time, no model provides a strong statistical framework to deal with switches between selection processes at individual sites during the course of evolution. This paper describes an approach that allows the site-specific selection process to vary along lineages of a phylogenetic tree. The parameters of the switching model of codon substitution are estimated by using maximum likelihood. The analysis of eight HIV-1 env homologous sequence data sets shows that this model provides a significantly better fit to the data than one that does not take into account switches between selection patterns in the phylogeny at individual sites. We also provide strong evidence that the strength and the frequency of occurrence of selection might not be estimated accurately when the site-specific variation of selection regimes is ignored.