Median Absolute Performance Error Research Articles

Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study

Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and PLA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean PLA were controlled within the acceptable ranges (AP within 5 mmHg below target; PLA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2–3.8)] and PLA [3.6% (2.2–5.7)]. The system decreased MVO2 and PLA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and PLA to avoid circulatory collapse, and reduced MVO2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted.

Accuracy of a universal theoretical formula for power calculation in pediatric intraocular lens implantation.

To compare the accuracy of Barrett Universal II formula with other formulas (Holladay 2, Hoffer Q, and SRK/T formulas) in the prediction of postoperative refraction for pediatric intraocular lens implantation. Academic medical center/children's hospital, San Francisco, California. Retrospective case series. Children aged 16 years or younger who underwent cataract extraction and IOL implantation (2012 to 2019) and had refraction assessed at 3 to 16 weeks postoperatively were included. Prediction error (PE) was calculated as postoperative mean spherical equivalent minus the target refraction. Mean, median, and standard deviation was calculated for PE and absolute PE. Performance across covariables (axial length, age, biometry type, keratometry, etc.) was studied, and a multivariate regression analysis was performed using a single prediction model for each formula. Sixty-four eyes of 64 patients, aged 1.5 to 15.5 years, were included. Barrett Universal II formula had the lowest mean PE (-0.22 diopters [D]), SD (1.18 D), median PE (-0.26 D), and median absolute PE (0.71) compared with those of the other formulas. Holladay 2 formula performed similarly to Barrett Universal II formula, and SRK/T formula had the greatest mean PE (-0.50 D) and SD (1.22 D). Barrett Universal II formula predictions were stable across all variables. Barrett Universal II formula demonstrated similar or superior performance when compared with other formulas in this pediatric study. Holladay 2 formula performed similarly to Barrett Universal II formula, and SRK/T formula had the least reliable performance, across several key biometric characteristics. Although PEs can be highly variable in pediatric populations, this study supports Barrett Universal II formula as a reasonable and reliable option for lens power calculation in children, including those with extreme biometric measurements.

Ray-tracing Calculation Using Scheimpflug Tomography of Diffractive Extended Depth of Focus IOLs Following Myopic LASIK.

To evaluate a ray-tracing formula for intraocular lens (IOL) calculation of diffractive extended depth of focus IOLs after myopic laser in situ keratomileusis (LASIK) compared to formulas from an established online calculator. This retrospective, consecutive case series included patients after cataract surgery with implantation of an extended depth of focus (EDOF) IOL (AT LARA, Carl Zeiss Meditec; Symfony, Johnson & Johnson) and a history of myopic LASIK. Preoperative assessments included biometry (IOLMaster; Carl Zeiss Meditec) and corneal tomography, including true net power (TNP) (Pentacam; Oculus Optikgeräte GmbH). To evaluate the measurements, the simulated keratometry values (SimK) were compared to the TNP. Regarding IOL calculation, the mean prediction error, mean and median absolute prediction error (MAE and MedAE), and number of eyes within ±0.50, ±1.00, and ±2.00 diopters (D) from the Haigis-L, Shammas, and Barrett True K No History formulas to the Potvin-Hill and Haigis with TNP (Pentacam) formulas were compared. Thirty-six eyes matched the inclusion criteria with a mean spherical equivalent of -6.26 ± 3.25 diopters (D) preoperatively and -0.79 ± 0.75 D postoperatively. The mean difference from SimK and TNP was significantly different from zero (P < .001; -1.24 ± 0.81 D). The best performing formulas by MedAE were the Potvin-Hill and Barrett True K No History (0.39 ± 0.78 and 0.64 ± 1.00 D). The formula with the most eyes within ±0.50 D was the Potvin-Hill (64%), followed by the Barrett True K No History (44%). For MAE and percentage of eyes within ±0.50 D, the Potvin-Hill formula was significantly better than the Haigis-L, Shammas, and Haigis-TNP formulas (P < .05). Calculation of IOLs in patients who had LASIK remains less predicable than calculations for virgin eyes. Using ray-tracing to calculate diffractive EDOF IOLs after myopic LASIK, the Potvin-Hill formula outperformed established formulas in terms of the percentage within target refraction and the MAE. [J Refract Surg. 2021;37(4):231-239.].

Systematic external evaluation of reported population pharmacokinetic models of vancomycin in Chinese children and adolescents.

Various population pharmacokinetic (PopPK) models for vancomycin in children and adolescents have been constructed to optimize the therapeutic regimen of vancomycin. However, little is known about their predictive performance when extrapolated to different clinical centres. Therefore, the aim of this study was to externally validate the predictability of vancomycin PopPK model when extrapolated to different clinical centres and verify its applicability in an independent data set. The published models were screened from the literature and evaluated using an external data set of a total of 451 blood concentrations of vancomycin measured in 220 Chinese paediatric patients. Prediction- and simulation-based diagnostics and Bayesian forecasting were performed to evaluate the predictive performance of the models. Ten published PopPK models were assessed. Prediction-based diagnostics showed that none of the investigated models met all the standards (median prediction error (MDPE) ≤ ±20%, median absolute prediction error (MAPE) ≤30%, PE% within ±20% (F20 ) ≥35% and PE% within ±30% (F30 ) ≥50%), indicating unsatisfactory predictability. In simulation-based diagnostics, both the visual predictive checks (VPC) and the normalized prediction distribution error (NPDE) indicated misspecification in all models. Bayesian forecasting results showed that the accuracy and precision of individual predictions could be significantly improved with one or two prior observations, but frequent monitoring might not be necessary in the clinic, since Bayesian forecasting identified that greater number of samples did not significantly improve the predictability. Model 3 established by Moffett et al showed better predictability than other models. The 10 published models performed unsatisfactorily in prediction- and simulation-based diagnostics; none of the published models was suitable for designing the initial dosing regimens of vancomycin. Pharmacokinetic characteristics and covariates, such as weight, renal function, age and underlying disease should be taken into account when extrapolating the vancomycin model. Bayesian forecasting combined with therapeutic drug monitoring based on model 3 can be used to adjust vancomycin dosing regimens.

External Evaluation of Vancomycin Population Pharmacokinetic Models at Two Clinical Centers

Background: Numerous vancomycin population pharmacokinetic models in neonates have been published; however, their predictive performances remain unknown. This study aims to evaluate their external predictability and explore the factors that might affect model performance. Methods: Published population pharmacokinetic models in neonates were identified from the literature and evaluated using datasets from two clinical centers, including 171 neonates with a total of 319 measurements of vancomycin levels. Predictive performance was assessed by prediction- and simulation-based diagnostics and Bayesian forecasting. Furthermore, the effect of model structure and a number of identified covariates was also investigated. Results: Eighteen published pharmacokinetic models of vancomycin were identified after a systematic literature search. Using prediction-based diagnostics, no model had a median prediction error of ≤ ± 15%, a median absolute prediction error of ≤30%, and a percentage of prediction error that fell within ±30% of >50%. A simulation-based visual predictive check of most models showed there were large deviations between observations and simulations. After Bayesian forecasting with one or two prior observations, the predicted performance improved significantly. Weight, age, and serum creatinine were identified as the most important covariates. Moreover, employing a maturation model based on weight and age as well as nonlinear model to incorporate serum creatinine level significantly improved predictive performance. Conclusion: The predictability of the pharmacokinetic models for vancomycin is closely related to the approach used for modeling covariates. Bayesian forecasting can significantly improve the predictive performance of models.

Prophylactic norepinephrine infusion for postspinal anesthesia hypotension in patients undergoing cesarean section: A randomized, controlled, dose-finding trial.

Prophylactic norepinephrine infusion effectively lowers the incidence of postspinal anesthesia hypotension. The optimal prophylactic dose of norepinephrine remains undefined. The purpose of this study was to investigate the optimal prophylactic dose of norepinephrine to prevent postspinal anesthesia hypotension in patients undergoing cesarean section. Prospective, double-blind, randomized, controlled, dose-finding trial. Operating room from March 2020 to June 2020. Ninety nine primipara or multipara women 18 - 40 years of age, singleton pregnancy ≥ 37 weeks, American Society of Anesthesiologists' physical status 1 or 2, scheduled for elective cesarean section under spinal anesthesia were included in this study. Patients were randomly assigned into groups to receive normal saline (NS) or one of four different prophylactic doses (0.025 [NE25], 0.05 [NE50], 0.075 [NE75], and 0.1 [NE100] ug/kg/min) of norepinephrine. The primary end point was the incidence of postspinal anesthesia hypotension (systolic blood pressure [SBP] < 80% of baseline) within 15 min after spinal anesthesia. Secondary outcomes included the overall stability of SBP control versus baseline (median performance error [MDPE] and median absolute performance error [MDAPE]), the dose that would be effective in preventing postspinal anesthesia hypotension in 50% (effective dose, ED 50) and 90% (ED90) of patients, other adverse events (bradycardia, nausea, vomiting, hypertension, and the total additional bolus of norepinephrine and atropine), and neonatal outcomes (blood gas values and Apgar scores). The incidence of postspinal anesthesia hypotension in NS, NE25, NE50, NE75, and NE100 groups was 68.42% (13/19), 40.00% (8/20), 20.00% (4/20), 15.00% (3/20), and 10.00% (2/20), respectively. With increasing prophylactic doses of norepinephrine, the incidence of postspinal anesthesia hypotension decreased (p < 0.001), SBP was maintained closer to the baseline (MDPE, p < 0.001; MDAPE, p = 0.001), and the total additional bolus of norepinephrine decreased (p < 0.001). The ED50 and ED90 values of norepinephrine were 0.016 (95% CI: -0.014 - 0.033) and 0.088 (95% CI: 0.068 - 0.133) ug/kg/min, respectively. Other adverse effects, neonatal outcomes, and the total additional bolus of atropine did not differ among the five groups. A prophylactic dose of 0.05 or 0.075 μg/kg/min norepinephrine prevents postspinal anesthesia hypotension in patients undergoing cesarean section.

A Comparison of Intraocular Lens Power Calculation Formulas in High Myopia.

To comparatively evaluate the accuracy of newer intraocular lens (IOL) calculation formulas and common third-generation formulas after Wang-Koch adjustment in the prediction of postoperative refraction in highly myopic eyes. This was a retrospective study including eyes with high myopia that had uncomplicated cataract surgery with implantation of an AcrySof MA60MA IOL (power range: -5.00 to +5.00 diopters [D]) (Alcon Laboratories, Inc). All patients underwent optical biometry (Carl Zeiss IOLMaster 500 and IOLMaster 700, and Allegro Biograph) and the postoperative spherical equivalent for the implanted IOL was estimated using SRK/T, Holladay 1 (both Wang-Koch adjusted), Haigis, Barrett Universal II, Kane, Ladas, and Hill-RBF v2.0 formulas. Outcomes included the median absolute prediction error (MedAE) and the proportion of eyes within ±0.25, ±0.50, and ±1.00 D of the preoperative prediction. Eighty-two eyes with a mean axial length of 30.89 ± 1.85 mm were included. The MedAE in ascending order was Hill-RBF v2.0 0.31 D, Kane 0.33 D, Barrett 0.36 D, Holladay Iwk 0.37 D, SRK/Twk 0.37 D, Holladay Iwk 0.43 D, HaigisULIB 0.54 D, and Ladas 0.61 D. The formula with the lowest MedAE (Hill-RBF v2.0) yielded a prediction error within ±0.25, ±0.50, and ±1.00 D in 43.1%, 70.6%, and 94.1% of cases, respectively. Recent formulas such as Barrett Universal II, Kane, and Hill-RBF v2.0 and Wang-Koch adjusted formulas perform well in this subset of patients with high myopia. The Hill-RBF v2.0 formula had the lowest MedAE and highest proportion of eyes within ±0.25, ±0.50, and ±1.00 D of the predicted target. [J Refract Surg. 2021;37(3):207-211.].

Prediction accuracy of standard and total keratometry by swept-source optical biometer for multifocal intraocular lens power calculation

We aimed to compare the refractive outcomes of cataract surgery with diffractive multifocal intraocular lenses (IOLs) using standard keratometry (K) and total keratometry (TK). In this retrospective observational case series study, a total of 302 patients who underwent cataract surgery with multifocal IOL implantation were included. Predicted refractive outcomes were calculated based on the current standard formulas and a new formula developed for TK using K and TK, which were obtained from a swept-source optical biometer. At 2-month postoperatively, median absolute prediction errors (MedAEs) and proportion of eyes within ± 0.50 diopters (D) of predicted postoperative spherical equivalent (SE) refraction were analyzed. There was no significant difference between MedAEs or proportion of eyes within ± 0.50D of predicted refraction from K and TK in each formula. In TFNT00 and 839MP IOL cases, there was no difference between MedAEs from K and TK using any formula. In 829MP IOL cases, MedAE from TK was significantly larger than that from K in Barrett Universal II/Barrett TK Universal II (P = 0.033). In 677MY IOL cases, MedAE from TK was significantly larger than that from K in Haigis (P = 0.020) and Holladay 2 (P = 0.006) formulas. In the subgroup analysis for IOL, there was no difference between the proportion of eyes within ± 0.50 D of predicted refraction from K and TK using any formula. TFNT00 and 839MP IOLs were favorable with TK, with 677MY IOL with K and 829MP IOL being in a neutral position, which necessitates the study that investigates the accuracy of the new TK technology.

Project hyperopic power prediction: accuracy of 13 different concepts for intraocular lens calculation in short eyes

PurposeTo evaluate the accuracy of intraocular lens (IOL) power calculation in a patient cohort with short axial eye length to assess the performance of IOL power calculation schemes in strong...

Relationship between blood pressure stability and mortality in cardiac surgery patients: retrospective cohort study.

Performance measurement variables can be applied in clinical practice to evaluate hemodynamic instability. This study aimed to evaluate the relationship between the performance measurement of mean arterial pressure during cardiac surgery using cardiopulmonary bypass and postoperative mortality. A retrospective cohort study of patients who underwent cardiac surgery requiring cardiopulmonary bypass between 2013 and 2016 was conducted. The median performance error (MDPE) and median absolute performance error (MDAPE) were calculated using the preoperative mean arterial pressure as a reference, and intraoperative mean arterial pressures as measured values. Multivariable logistic regression analyses were performed using performance measurement variables to predict 30-day mortality. Overall survival according to performance measurement variables was evaluated using Cox proportional hazard models and Kaplan-Meier survival curves were generated to compare survival probability. Among 1203 patients, 110 (9.1%) died after surgery, and the 30-day mortality rate was 2.3% (28/1203). After adjusting for confounders, MDPE and MDAPE were significant mean arterial pressure derived predictors of 30-day mortality and overall survival. Intraoperative hypotension measured by performance measurement variables was independently associated with 30-day and overall mortality after cardiac surgery requiring cardiopulmonary bypass. Kaplan-Meier survival curves showed lower survival probability in patients with higher MDAPE during the pre- and post- cardiopulmonary bypass periods (P < 0.001 by log-rank test). Intraoperative hypotension measured by performance measurement variables was independently associated with 30-day and overall mortality after cardiac surgery requiring CPB. We propose that performance measurement variables are useful for quantifying the degree of intraoperative hypotension and predicting survival following cardiac surgery.Trial registration: ClinicalTrials.gov, identifier: NCT03785132.

Effect of Hemodilution on Fluctuation of Cerebral Oxygen Saturation during Cardiopulmonary Bypass in Children with Cyanotic Congenital Heart Disease

Background: In patients with cyanotic congenital heart disease (CHD), cerebral oxygenation may be maintained by elevations in hematocrit (Hct). Hemodilution accompanying cardiopulmonary bypass (CPB), however, can disrupt cerebral oxygen balance, leading to fluctuations in cerebral oxygen saturation (ScO2). The present study investigated the effects of Hct changes on the fluctuation of ScO2 during CPB in cyanotic CHD using performance measurement (PM). Methods: Children with CHD (51 acyanotic and 46 cyanotic) who had undergone cardiac surgery using CPB were enrolled. Median performance error (MDPE), median absolute performance error (MDAPE), and wobble parameters of ScO2 were calculated before (reference value), during, and after CPB. Correlations of PM parameters with Hct and reductions in Hct (ΔHct) were also evaluated. Results: Before CPB, patients with cyanotic CHD had lower MDPE and larger wobble than those with acyanotic CHD, although mean ScO2 did not differ significantly between the two groups. During CPB, ScO2 of acyanotic CHD increased as ΔHct increased, but PM variables were not associated with ΔHct. In cyanotic CHD, MDPE (r = −0.324, p = 0.032) and MDAPE (r = 0.339, p = 0.024) correlated significantly with ΔHct during CPB. After CPB, MDPE (r = 0.574, p = 0.025) and MDAPE (r = −0.543, p = 0.036) were significantly correlated with Hct in children with cyanotic CHD who underwent palliative surgery. Conclusion: Therefore, ScO2 fluctuation during CPB in children with cyanotic CHD may be affected by the decrease in Hct, suggesting that excessive hemodilution can negatively influence the maintenance of cerebral oxygenation in these patients.

Evaluation of Bayesian Forecasting Methods for Prediction of Tacrolimus Exposure Using Samples Taken on Two Occasions in Adult Kidney Transplant Recipients.

Bayesian forecasting-based limited sampling strategies (LSSs) for tacrolimus have not been evaluated for the prediction of subsequent tacrolimus exposure. This study examined the predictive performance of Bayesian forecasting programs/services for the estimation of future tacrolimus area under the curve (AUC) from 0 to 12 hours (AUC0-12) in kidney transplant recipients. Tacrolimus concentrations were measured in 20 adult kidney transplant recipients, 1 month post-transplant, on 2 occasions one week apart. Twelve samples were taken predose and 13 samples were taken postdose at the specified times on the first and second sampling occasions, respectively. The predicted AUC0-12 (AUCpredicted) was estimated using Bayesian forecasting programs/services and data from both sampling occasions for each patient and compared with the fully measured AUC0-12 (AUCmeasured) calculated using the linear trapezoidal rule on the second sampling occasion. The bias (median percentage prediction error [MPPE]) and imprecision (median absolute prediction error [MAPE]) were determined. Three programs/services were evaluated using different LSSs (C0; C0, C1, C3; C0, C1, C2, C4; and all available concentrations). MPPE and MAPE for the prediction of fully measured AUC0-12 were <15% for each program/service (with the exclusion of when only C0 was used), when using estimated AUC from data on the same (second) occasion. The MPPE and MAPE for the prediction of a future fully measured AUC0-12 were <15% for 2 programs/services (and for the third when participants who had a tacrolimus dose change between sampling days were excluded), when the occasion 1-AUCpredicted, using C0, C1, and C3, was compared with the occasion 2-AUCmeasured. All 3 Bayesian forecasting programs/services evaluated had acceptable bias and imprecision for predicting a future AUC0-12, using tacrolimus concentrations at C0, C1, and C3, and could be used for the accurate prediction of tacrolimus exposure in adult kidney transplant recipients.

Comparison of the accuracy of intraocular lens power calculation formulas for eyes after corneal refractive surgery.

In cataract surgery, calculating intraocular lens (IOL) power in patients who have previously received corneal refractive surgery on the same eye presents a clinical challenge. This study aims to compare the accuracy of the Haigis-L, Barrett True-K, and Shammas-PL formulas in predicting the IOL power in eyes following corneal refractive surgery. This study analyzed 32 eyes belonging to 28 patients who underwent cataract surgery and IOL implantation after previously undergoing myopic corneal refractive surgery. The IOL power was calculated using the Haigis-L, Barrett True-K, and Shammas-PL formulas, and the accuracy of the three formulas was compared. The Haigis-L, Barrett True-K, and Shammas-PL formulas had a mean arithmetic IOL prediction error of -0.65, -0.39, and -0.46, respectively. The mean numerical errors of the three formulas were significantly different from zero (P<0.001). The smallest median absolute refraction prediction error (median =0.40) belonged to the Barrett True-K formula, which was significantly smaller than that of the Haigis-L formula (median =0.57, P<0.05) but similar to that of the Shammas-PL formula (median =0.49, P>0.05). There was no significant difference in the percentage of eyes within either ±0.50 D or ±1.00 D of the predicted refraction error across the three formulas. The Barrett True-K formula can predict IOL power in eyes that have previously undergone myopic corneal refractive surgery better than the Haigis-L formula.

Influence of Remifentanil on the Control Performance of the Bispectral Index Controlled Bayesian-Based Closed-Loop System for Propofol Administration.

This study investigated the clinical performance of a model-based, patient-individualized closed-loop (CL) control system for propofol administration using the bispectral index (BIS) as a controlled variable during the induction and maintenance of anesthesia with propofol and remifentanil and studied the influence of the targeted effect-site concentration of remifentanil (CeREMI) on its clinical performance. In 163 patients, propofol was administered using a CL system (BIS target [BISTARGET] between 40 and 50). Initial CeREMI targets between 2 and 7.5 ng/mL were selected as deemed clinically required. Performance parameters during induction were the time required to initially cross the target BIS, the time required to reach the maximal drug effect after induction (TPEAK, BIS) and the corresponding BIS at this moment, and the time required to regain the target BIS at the end of induction. Performance during maintenance was defined as the percentage of case time with target BIS ± 10 from target and the amount of performance error (PE) between the observed and target BIS values and its derived median PE (MDPE) as a measure of control bias, median absolute PE (MDAPE) as a measure of control inaccuracy, divergence as a measure of the time-related trend of the measured BIS values relative to the target BIS values, and wobble as a measure of intrasubject variability in prediction error. The secondary end point was the hemodynamic stability of the patient during CL control. The applied CL system induced and maintained anesthesia within clinically accepted ranges. The percentage of case time [mean (standard deviation [SD]) across all study participants] with BIS ± 10 from the target was 82% (14%). The mean (SD) population MDPE and MDAPE were -6.6% (5.5%) and 11.2% (5.5%), respectively. A negative divergence [-0.001 (0.004)] and acceptable wobble [9.7% (4.0%)] were found. The correlation between the system PE and CeREMI was low and only influenced by a CeREMI <2.8 ng/mL. Hemodynamic stability stayed within the clinically acceptable range. The applied CL system for propofol administration has an acceptable performance in the CeREMI range of 2.8-7.5 ng/mL during the induction and maintenance of anesthesia. There was no evidence of a strong association between CeREM and the CL performance. This study also shows that when the CeREMI is <2.8 ng/mL, it might be more challenging to prevent arousal during propofol anesthesia.

Effect of Mandatory IFRS Adoption on Accounting-Based Prediction Models for CDS Spreads

In this study, we examine the effects of mandatory IFRS adoption on accounting-based prediction models of CDS spreads for a sample of 292 firms in 16 countries. In our examination, we estimate the models for both financial and nonfinancial firms before and after mandatory IFRS adoption. We find that mean and median absolute percentage prediction errors are larger for both financial and non-financial firms after mandatory IFRS adoption. We also estimate accounting-based prediction models of CDS spreads separately for financial and non-financial US firms as a benchmark. Although US firms also show an increase in the mean and median absolute percentages of prediction errors over the same period, our findings from regressions that use a difference-in-difference design indicate that the increase is significantly greater for firms in countries that adopted IFRS mandatorily. We also find that in the post-adoption period, prediction errors are larger for firms in countries with weaker institutions such as low levels of property rights and more restrictive access to credit.

Application of Reticulocyte-Based Estimation of Red Blood Cell Lifespan in Anemia Management of End-Stage Renal Disease Patients.

Shortened red blood cell (RBC) lifespan is one of the major factors contributing to anemia in end-stage renal disease (ESRD) patients and should be taken into account in anemia management protocols. In this study, we aimed to estimate RBC lifespan and the source of between-subject variability in ESRD patients. The resulting individual parameters (empirical Bayes estimates) were used to predict hemoglobin concentrations 2weeks in advance. The reticulocyte-based estimation of RBC lifespan (REBEL) and the population modeling of RBC count data were used. A total of 120 blood samples collected biweekly over 10weeks in 24 patients receiving maintenance doses of recombinant human erythropoietin (rHuEPO) subcutaneously were included in this analysis. Typical RBC lifespan was estimated to be 63.3days. RBC lifespan was found to increase with erythroferrone, a recently identified hormone participating in iron metabolism. Approximately, a 10% increase in plasma erythroferrone was associated with a 5% increase in RBC lifespan. In addition, RBC lifespan was 18.7% shorter in females compared with males. Out of 24 subjects, 16 had hemoglobin concentrations predicted within 95% prediction intervals. The median absolute prediction error was 15.9% (interquartile range, 9.5 to 24.7%). We demonstrated that REBEL coupled with the population modeling technique can be used effectively to estimate RBC lifespan. Then, individual parameters can be used to predict future hemoglobin concentrations in ESRD patients.

A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication.

Solithromycin is a fourth-generation macrolide antibiotic with potential efficacy in pediatric community-acquired bacterial pneumonia. Pharmacokinetic (PK) studies of solithromycin in pediatric subjects are limited, therefore application of minimally invasive drug sampling techniques, such as dried blood spots (DBS), may enhance the enrollment of children in PK studies. The objectives of this study were to compare solithromycin concentrations in DBS with those in liquid plasma samples (LPS) and to quantify the effects of modeling DBS concentrations on the results of a population PK model. Comparability analysis was performed on matched DBS and LPS solithromycin concentrations collected from two different phase 1 clinical trials of solithromycin treatment in children (clinicaltrials.gov #NCT01966055 and #NCT02268279). Comparability of solithromycin concentrations was evaluated based on DBS:LPS ratio, median percentage prediction error, and median absolute percentage prediction error. The effect of correcting DBS concentrations for both hematocrit and protein binding was investigated. In addition, a previously published population PK model (NONMEM) was leveraged to compare parameter estimates resulting from either DBS or LPS concentrations. A total of 672 paired DBS-LPS concentrations were available from 95 subjects (age: 0-17 years of age). The median (range) LPS and DBS solithromycin concentrations were 0.3 (0.01-12) mcg/mL and 0.32 (0.01-14) mcg/mL, respectively. Median percentage prediction error and median absolute percentage prediction error of raw DBS to LPS solithromycin concentrations were 5.26% and 22.95%, respectively. In addition, the majority of population PK parameter estimates resulting from modeling DBS concentrations were within 15% of those obtained from modeling LPS concentrations. Solithromycin concentrations in DBS were similar to those measured in LPS and did not require correction for hematocrit or protein binding.

The association between knee breadth and body mass: The Northern Finland Birth Cohort 1966 case study.

Body mass estimation from skeletal dimensions is a useful tool when studying archeological human samples. Bony articular surface dimensions of the lower limb have frequently been utilized to estimate body size. In the present study, we investigated the association between knee breadth and body mass in a Northern European population. Our study aimed to confirm both methodology and results presented in earlier studies. The study sample consists of 1,290 subjects belonging to the Northern Finland Birth Cohort 1966. Three knee breadth dimensions-femoral biepicondylar breadth, mediolateral breadth of femoral condyles, and mediolateral breadth of the tibial plateau-were measured from subjects' knee PA-radiographs. Measurements and their association with body weight at 31 years were utilized for creating body mass estimation equations using linear regression and reduced major axis regression. Correlations between knee measurements and body weight at three different ages (18, 31, and 46) were also analyzed. Positive associations were detected between each knee breadth variable and weight in the total sample and both genders separately. Body mass estimation equations were created for the total sample, for males and for females. R values of the models ranged from 0.38 to 0.74. Median absolute percent prediction errors ranged from 6.89 to 9.72%. The highest correlations were obtained between knee breadth and body weight in early adulthood. Our large sample confirmed that equations derived from knee breadth dimensions are accurate when estimating body mass of modern humans. Knee breadth measurements clearly have a positive association with body weight in early maturity.

Predicting radiation dosimetric distribution in different regions of the jaw in patients receiving radiotherapy for squamous cell carcinoma of the tonsil.

Radiotherapy (RT), the main treatment for patients with head and neck cancer, can lead to dental complications. We identified 244 patients with squamous cell carcinoma of the tonsil treated with RT from 2004 to 2013. For each patient, we contoured the 10 tooth-bearing regions and calculated the radiation dose (gray, Gy) to each region. From this data set, we built two predictive models to determine the expected maximum radiation dose, one for the non-molar regions and another for the molar regions. For the non-molars, the final model included location, T-classification, and overall stage, with a median absolute prediction error of 7.0 Gy. For the molars, the final model included location, T-classification, overall stage, and treatment year, with a median absolute error of 6.0 Gy. Our current model offers a good estimation of the maximum radiation dose delivered to different regions of the jaw; future work will independently validate these models.

Accuracy and Precision of Intraocular Lens Calculations Using the New Hill-RBF Version 2.0 in Eyes With High Axial Myopia

To compare the accuracy and precision of the new Hill-RBF version 2.0 (Hill-RBF 2) formula with other formulas (Barrett Universal II, Haigis, Hoffer Q, Holladay 1, and SRK/T) in predicting residual refractive error after phacoemulsification in high axial myopic eyes. Retrospective case series. 127 eyes of 127 patients with axial length (AL) ≥26mm were included. The refractive prediction error (PE) was calculated as the difference between the postoperative refraction and the refraction predicted by each formula for the intraocular lens (IOL) power actually implanted. Standard deviation (SD) of PE, median absolute PE (MedAE), proportion of eyes within ±0.25, ±0.50, and ±1.00 diopter (D) of PE were compared. A generalized linear model was used to model the mean function and variance function of the PE (indicative of the accuracy and precision) with respect to biometric variables. The MedAE and SD of Hill-RBF 2 were lower than that of Hoffer Q, Holladay 1, and SRK/T (P≤ .036) and were comparable to Barrett Universal II and Haigis (P ≥ .077). Hill-RBF 2 had more eyes within ±0.25 D of the intended refraction (76 out of 127 eyes [59.84%]) compared to other formulas (P ≤ .034) except Barrett Universal II (P= .472). AL was associated with the mean function or variance function of the PE for all formulas except Hill-RBF 2. In this study, the precision of Hill-RBF 2 is comparable to Barret Universal II and Haigis. Unlike the other 5 formulas, its dispersion and the accuracy of the refractive prediction is independent of the AL.