Patient Dose Research Articles

Enoxaparin Venous Thromboembolism Prophylaxis Dosing in Critically Ill Underweight Patients

Purpose: Optimal dosing of VTE prophylaxis for specific patient populations remains an area of concern as insufficient evidence exists regarding dosing for underweight patients. The purpose of this study is to compare the incidence of major bleeding events in underweight patients given different prophylactic doses of enoxaparin. Methods: This is a retrospective analysis performed at multiple hospitals within a single health care system. Patients with a BMI < 18.5 kg/m2 were divided into 2 groups depending on whether they received at least 1 prophylactic dose of enoxaparin 30 mg subcutaneously once daily or enoxaparin 40 mg subcutaneously once daily. Underweight adult patients were included if they were admitted to an ICU for at least 48 hours and received at least 1 dose of enoxaparin for VTE prophylaxis during their ICU admission. The primary aim was to compare the incidence of clinically significant bleeding between dosing strategies. Secondary aims included the incidence of VTE during admission, ICU length of stay, overall hospital length of stay, and all-cause mortality 30 days post-discharge. Results: A total of 310 patients met inclusion criteria for this study, with 80 patients in the 30 mg group and 230 patients in the 40 mg group. There was no significant difference in major bleeding events between the 2 groups ( P = .61). No significant differences in incidence of VTE ( P = .455 ), ICU length of stay ( P = .466), overall hospital stay ( P = .502), or all-cause mortality ( P = .925) were found between groups. Conclusions: No difference was found in clinically significant bleeding between underweight critically ill patients receiving VTE prophylaxis with enoxaparin 30 mg once daily or 40 mg once daily. Further studies are needed to evaluate the optimal dosing of VTE prophylaxis with enoxaparin in underweight patients.

Dosage Optimization Using Physiologically Based Pharmacokinetic Modeling for Pediatric Patients with Renal Impairment: A Case Study of Meropenem.

The pharmacokinetics of renally eliminated antibiotics can be influenced by changes associated with renal function and development in a growing subject. Little is known about the effects of renal insufficiency on the pharmacokinetics of meropenem in pediatric subjects. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of meropenem for pediatric patients that can be used to optimize meropenem dosing in pediatric patients with renal impairment (RI). The PBPK model was developed using GastroPlus™ 9.9 based on clinical data obtained from the literature and then scaled to pediatric patients with RI for dose optimization of meropenem. The goodness of fit of the model was assessed by comparing the predicted values of AUC0-t, AUC0-α, and Cmax with the observed data and the average fold errors (AFE). The AFE values for AUC0-t, AUC0-α, and Cmax in the pediatric population were measured to be 1.60, 1.08, and 1.48, respectively. In addition, dose optimization was performed in virtual pediatric populations with varying degrees of RI and a dose reduction to 10mg/kg and 7.5mg/kg was recommended for moderate and severe RI, respectively. In all virtual pediatric populations with RI, the plasma concentration reached the recommended time above the minimum inhibitory concentration (MIC) at all optimized doses. The developed PBPK model for meropenem provides a quantitative tool to assess the impact of RI on the pharmacokinetics of meropenem in pediatric patients, which may be useful for optimizing the dosing regimen.

Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies. To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles. We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior. We employed the model for exposure-response evaluation and for investigating doses in paediatric patients to match the adult exposure at the labelled dose. At Week 30, 104/129 (81%) children (53% female and 47% Crohn disease) remained on vedolizumab, of whom 39 (31%) in the exposure-response evaluation were in deep biochemical remission. Increased baseline drug clearance was associated with lower deep biochemical remission rates at Week 30 based on ESR/CRP (OR 0.47 [95% CI 0.2-1.05, p = 0.08]) and calprotectin < 100 μg/g (OR 0.13 [95% CI 0.1-0.79, p < 0.05]). Higher weight and lower serum albumin were associated with increased clearance (p < 0.001). Simulation models found that, for children ≤ 30 kg, tiered fixed dosing regimens best matched adult drug concentrations. Drug clearance was strongly influenced by serum albumin. Baseline clearance predicted deep biochemical remission at Week 30. Further investigation is needed to better understand optimal dosing strategies-especially for lower-weight children receiving vedolizumab.

Comparison of 4-factor fixed dose versus 4-factor weight-based dose prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis.

The objective of this systematic review and meta-analysis is to evaluate the efficacy, safety, time to INR reversal, total volume of 4-factor prothrombin complex concentrate (PCC) administered of fixed-dose versus weight-based dosing strategies in patients requiring urgent warfarin reversal, with specific focus on clinical outcomes such as hemostatic efficacy, thromboembolic events, and mortality rates. A comprehensive systematic review was conducted using the PubMed, Embase, and Cochrane databases from inception through October 2023. We searched for randomized clinical trials or observational studies that compared efficacy or safety outcomes of fixed-dose vs. variable 4-PCC dose in adult patients. A total of fourteen studies were included. The overall use of fixed-dose 4-PCC was associated with a lower likelihood of reaching the INR goal (RR = 0.84, 95% CI 0.80 - 0.89) and a significantly higher proportion of patients (169 out of 651 [26%]) required an additional dose of 4-PCC compared to the variable-dose group. The rate of mortality (RR = 0.85, 95% CI 0.70 - 1.03) and thromboembolic events (RR = 1.27, 95% CI 0.65 - 2.45) were similar between the two treatment groups. This systematic review and meta-analysis showed that variable dosing of 4-PCC more successfully achieves the target INR for warfarin reversal compared to fixed dosing. However, both dosing strategies have similar mortality and thromboembolic rates. While fixed dosing offers a simpler approach, it may require additional dosing. Future studies should focus on optimizing dosing strategies to balance efficacy, safety, and practicality in various clinical scenarios.

Importance of Glomerular Filtration Rate Determination and its Role in Drug-Dose Adjustments with Special Reference to Oncology

Glomerular filtration Rate (GFR) measured in steady state is the best marker of kidney function. Glomerular filtration rate can be determined using exogenous markers like inulin, iothalamate, or iohexol (mGFR), or estimated using endogenous markers like creatinine and cystatin C (eGFR). Several equations are available, CKD-EPI equation is the recommended equation as per current guidelines. CKD-EPI creatinine equation refit (without the race variable) – 2021, and CKD-EPI creatinine - cystatin C equation refit (without the race variable)-2021 are the most recent recommendations from the National Kidney Foundation and the American Society of Nephrology. Dose modifications of many drugs are needed in kidney dysfunction. In chronic kidney disease, as the kidney function is stable, determination of GFR is more accurate and can be used to modify the drug doses. Since the kidney function is not stable in acute kidney injury, determination of GFR is more difficult and it is not accurate. This makes it difficult to use it for determining dose modifications of drugs. Therapeutic drug level monitoring, and adjusting the dose based on pharmacokinetics/pharmacodynamics knowledge of the drug could be helpful in such cases. In oncology, accurate GFR measurement is crucial for adjusting the doses of chemotherapeutic agents to avoid toxicity and ensure efficacy, as cancer patients often have compromised kidney function due to the disease or its treatment. In this manuscript, we review all these aspects to provide a comprehensive understanding of GFR measurement and its implications in drug-dose adjustments, with a particular focus on how accurate GFR assessment is essential for optimizing chemotherapy dosing in oncology patients to minimize toxicity and maximize therapeutic efficacy. Frequently, medical professionals need to depend on online calculators to get the value of eGFR, as these equations can be complicated. Scientific calculators can be used too, but that is not a common practice in nephrology clinics. The authors have shown in this paper how to use Microsoft Excel to create personal calculators, so that eGFR may be calculated by medical professionals and dialysis staff even when internet is not available due to institutional policies or otherwise. The ‘Appendix’ section given at the end of the paper shows how to create these personal calculators in Microsoft excel. Calculators for CKD-EPI equations can also be developed in excel, however the calculations are more complex, so I prefer using the programming language python to develop these calculators. In this paper, the authors have shown only the excel based calculators for CG equation and MDRD-4 (re-expressed) equation.

Comparing two-sample log-linear exposure estimation with Bayesian model-informed precision dosing of tobramycin in adult patients with cystic fibrosis.

Tobramycin dosing in patients with cystic fibrosis (CF) is challenged by its high pharmacokinetic (PK) variability and narrow therapeutic window. Doses are typically individualized using two-sample log-linear regression (LLR) to quantify the area under the concentration-time curve (AUC). Bayesian model-informed precision dosing (MIPD) may allow dose individualization with fewer samples; however, the relative performance of these methods is unknown. This single-center retrospective analysis included adult patients with CF receiving tobramycin from 2015 to 2022. Tobramycin concentrations were predicted using LLR or Bayesian estimation with two population PK models (Hennig and Alghanem). Then, both methods were used to estimate the AUC for simulated patients. For Bayesian estimation, AUC estimation with flattened priors and limited sampling strategies were also assessed. Predictions were evaluated using normalized root mean square error (nRMSE), mean percent error (MPE), and accuracy. The data set included 70 treatment courses, with 32 not evaluable by LLR due to detection limits or timing issues. Bayesian estimation demonstrated worse accuracy (47.1%-50.7% vs 75.7%), higher MPE (24.2%-32.4% vs -2.4%), and higher nRMSE (35.0%-39.4% vs 24.8%) than LLR for peak concentrations but performed better on troughs (accuracy: 92.0%-92.9% vs 84.6%). Bayesian estimation with flattened priors and a single sample at 4 h was comparable to LLR performance, with better accuracy (42.9%-68.0% vs 41.1% LLR), comparable MPE (-2.3% to -3.7% vs -0.5%) and nRMSE (11.3%-21.6% vs 17.3%). Bayesian estimation with one concentration and flattened priors can match LLR prediction accuracy. However, popPK models must be improved to better estimate peak samples.

CT material decomposition with contrast agents: Single or multiple spectral photon-counting CT scans? A simulation study.

With the widespread introduction of dual energy computed tomography (DECT), applications utilizing the spectral information to perform material decomposition became available. Among these, a popular application is to decompose contrast-enhanced CT images into virtual non-contrast (VNC) or virtual non-iodine images and into iodine maps. In 2021, photon-counting CT (PCCT) was introduced, which is another spectral CT modality. It allows for scans with more than two different detected spectra. With these systems, it becomes possible to distinguish more than two materials. It is frequently proposed to administer more than one contrast agent, perform a single PCCT scan, and then calculate the VNC images and the contrast agent maps. This may not be optimal because the patient is injected with a material, only to have it computationally extracted again immediately afterwards by spectral CT. It may be better to do an unenhanced scan followed by one or more contrast-enhanced scans. The main argument for the spectral material decomposition is patient motion, which poses a significant challenge for approaches involving two or more temporally separated scans. In this work, we assume that we can correct for patient motion and thus are free to scan the patient more than once. Our goal is then to quantify the penalty for performing a single contrast-enhanced scan rather than a clever series of unenhanced and enhanced scans. In particular, we consider the impact on patient dose and imagequality. We simulate CT scans of three differently sized phantoms containing various contrast agents. We do this for a variety of tube voltage settings, a variety of patient-specific prefilter (PSP) thicknesses and a variety of threshold settings of the photon-counting detector with up to four energy bins. The reconstructed bin images give the expectation values of soft tissue and of the contrast agents. Error propagation of projection noise into the images yields the image noise. Dose is quantified using the total CT dose index (CTDI) value of the scans. When combining multiple scans, we further consider all possible tube current (or dose) ratios between the scans. Material decomposition is done image-based in a statistical optimal way. Error propagation into the material-specific images yields the signal-to-noise ratio at unit dose (SNRD). The winning scan strategy is the one with the highest total SNRD, which is related to the SNRD of the material that has the lowest signal-to-noise ratio (SNR) among the materials to decompose into. We consider scan strategies with up to three scans and up to three materials (water W, contrast agent X and contrast agent Y). In all cases, those scan strategies yield the best performance that combine differently enhanced scans, for example, W+WX, W+WXY, WX+WXY, W+WX+WY, with W denoting an unenhanced scan and WX, WY and WXY denoting X-, Y-, and X-Y-enhanced scans, respectively. The dose efficiency of scans with a single enhancement scheme, such as WX or WXY, is far lower. The dose penalty to pay for these single enhancement strategies is about two or greater. Our findings also apply to scans with a single energy bin and thus also to CT systems with conventional, energy-integrating detectors, that is, conventional DECT. Dual source CT (DSCT) scans are preferable over single source CT scans, also because one can use a PSP on the high Kilovolt spectrum to better separate the detected spectra. For the strategies and tasks considered here, it does not make sense to simultaneously scan with two different types of contrast agents. Iodine outperforms other high Z elements in nearly allcases. Given the significant dose penalty when performing only one contrast-enhanced scan rather than a series of unenhanced and enhanced scans, one should consider avoiding the single-scan strategies. This requires to invest in the development of accurate registration algorithms that can compensate for patient and contrast agent motion between separatescans.

Incidence of surgical infection in cefazolin 3 g versus 2 g for colorectal surgery in obese patients.

To compare the incidence of surgical site infection (SSI) between cefazolin 3 g and 2 g surgical prophylaxis in patients weighing ≥120 kg that undergo elective colorectal surgery. A multicenter, retrospective cohort study was performed utilizing a validated database of elective colorectal surgeries in Michigan acute care hospitals. Adults weighing ≥120 kg who received cefazolin and metronidazole for surgical prophylaxis between 7/2012 and 6/2021 were included. The primary outcome was SSI, which was defined as an infection diagnosed within 30 days following the principal operative procedure. Multivariable logistic regression was used to identify variables associated with SSI; the exposure of interest was cefazolin 3 g surgical prophylaxis. A total of 581 patients were included; of these, 367 (63.1%) received cefazolin 3 g, while 214 (36.8%) received 2 g. Patients who received cefazolin 3 g had less optimal antibiotic timing (324 [88.3%] vs 200 [93.5%]; P = .043) and a higher receipt of at least 1 of the prophylaxis antibiotics after incision (22 [6%] vs 5 [2.3%]; P = .043). There was no SSI difference between cefazolin 3 g and 2 g cohorts (23 [6.3%] vs 16 [7.5%], P = .574). When accounting for age, smoking status, and surgical duration, cefazolin 3 g was not associated with a reduction in SSI (adjOR, .64; 95%CI, .32-1.29). Surgical prophylaxis with cefazolin 3 g, in combination with metronidazole, was not associated with decreased SSI compared to 2 g dosing in obese patients undergoing elective colorectal surgery.

Determination of Diagnostic reference levels (DRLs) for frontal chest radiology of adult patients at Regional Hospital Center of Daloa, Côte D'Ivoire

Although, diagnostic radiology is important in medical field, it significantly contributes to the irradiation of patients. One of the major goals of medical imaging is to minimize the radiation dose to the patient without compromising the image quality needed to produce an accurate diagnosis. Therefore, it is necessary to establish the diagnostic reference levels (DRLs) in radiology in order to achieve this goal. This study aimed to determine the DRLs for the chest radiological examination at the Regional Hospital of Daloa. A DAP meter was used to acquire the dose-area product (DAP) and air kerma data of 127 adult patients (≥ 18 years) undergoing chest examinations in the radiology room. Then the Entrance Surface Dose (ESD) calculated by weighting the dose in air by the BSF backscatter factor and DRLs in DAP and ESD were determined with the 75th percentile statistical method. The key findings showed a variation of 2.69 to 500.47cGy.cm2 and 0.388 to 10.104 mGy respectively for DAP and ESD with means of 52.314 cGy.cm2 and 2.279 mGy respectively. The respective values of DRL in DAP and ESD found in this work were 60.91 cGy.cm2 and 2.658 mGy. The comparison of the DRL values in DAP and ESD found in this work with others values has shown that they were lower than the national and international values of DRLs. This study was essential for RHC of Daloa because it has evaluated the patient doses and indicated that these doses are quietly optimized.

Comparison of ZnS(Ag) Scintillator and Proportional Counter Tube for Alpha Detection in Thin-Layer Chromatography

(1) Background: Targeted alpha therapy is an emerging field in nuclear medicine driven by two advantages: overcoming resistance in cancer-suffering patients to beta therapies and the practical application of lower activities of 212Pb- and 225Ac-labelled peptides to achieve the same doses compared to beta therapy due to the highly cytotoxic nature of alpha particles. However, quality control of the 212Pb/225Ac-radiopharmaceuticals remains a challenge due to the low activity levels used for therapy (100 kBq/kg) and the formation of several free daughter nuclides immediately after the formulation of patient doses; (2) Methods: The routine alpha detection on thin-layer chromatograms (TLC) of 212Pb- and 225Ac-labelled peptides using a MiniScanPRO+ scanner combined with an alpha detector head was compared with detection using an AR-2000 scanner equipped with an open proportional counter tube. Measurement time, resolution and validity were compared for both scanners; (3) Results: For 225Ac, the quality control values of the radiochemical purity (RCP) were within the acceptance criteria 2 h after TLC development, regardless of when the TLC probe was taken. That is, if the TLC probe was taken 24 h after radiosynthesis, the true value of the RCP was not measured until 5 h after TLC development. For 212Pb-labelled peptides, the probe sampling did not have a high impact on the value of the RCP for the MiniScanPRO+ and AR-2000. A difference was observed when measuring TLC with the AR-2000 in different modes; (4) Conclusions: The MiniScanPRO+ is fast, does not require additional equipment and can also measure the gamma spectrum, which may be important for some radiopharmaceutical production sites and regulatory authorities. The AR-2000 has a better signal-to-noise ratio, and this eliminates the need for additional waiting time after TLC development.

Increasing cumulative cabergoline dose in patients with prolactinoma improves metabolic parameters independently of decrease in prolactin levels

Objectives: In prolactinoma patients treated with cabergoline, all of whom achieved normoprolactinemia, longitudinal changes in metabolic parameters and the factors influencing these changes were investigated. Methods: This retrospective-longitudinal study was conducted at a pituitary disease center. Medical records of newly diagnosed prolactinoma patients between 2013 and 2023 were reviewed. After applying exclusion criteria, 102 prolactinoma patients were included in the final analysis. Clinical and laboratory parameters of prolactinoma patients were recorded. Metabolic parameters assessed were fasting plasma glucose, lipid levels, fasting insulin levels, HbA1c levels, and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) levels. Subsequently, metabolic parameters assessed at the initial and final visits were compared, and factors influencing these parameters were analyzed. Results: All prolactinoma patients were treated with cabergoline, and all were in remission at their final visit. The treatment significantly reduced fasting plasma glucose, HbA1c, and LDL cholesterol levels (P&amp;lt;0.05). Although there were improvements in other lipid parameters, fasting insulin, BMI, and HOMA-IR compared to baseline, the differences were not statistically significant. A correlation analysis was conducted to identify factors influencing fasting plasma glucose, HbA1c, and LDL cholesterol levels at the final visit in prolactinoma patients. The analysis revealed that only the cumulative dose of cabergoline significantly impacted all three metabolic parameters (P&amp;lt;0.05). Conclusions: Cabergoline not only balances prolactin levels but also directly improves metabolic health. Current and future evidence clearly indicates that dopamine agonists like cabergoline could be an effective treatment not only for patients with prolactinomas but also for individuals affected by metabolic disorders without hyperprolactinemia.

Effectiveness and safety of daily versus alternate-day rosuvastatin dose in dyslipidemic patients: a prospective, randomized and open-label study

Background: Dyslipidemia is considered to be an important risk factor for development of atherosclerotic cardiovascular disease (ASCVD). Statins, also called HMG CoA reductase inhibitors are considered to the most effective lipid lowering agents. This study assessed the effectiveness and safety of daily versus alternate day dosing regimens of rosuvastatin in dyslipidemia patients. Methods: This study was conducted for a period of 12 weeks. Study subjects comprised patients of either sex in age group 18-65 years diagnosed with dyslipidemia and a total of 90 subjects completed study who were randomly distributed to three groups, A (rosuvastatin 10 mg daily), B (rosuvastatin 10 mg on alternate days) and C (rosuvastatin 20 mg on alternate days). Results: Rosuvastain significantly lowered total cholesterol, low density lipoprotein-cholesterol and triglycerides in all groups (p&lt;0.001). High density lipoprotein-cholesterol increased, but non-significantly (p&gt;0.05). Intergroup differences were not statistically significant. Group A reported slightly more adverse events than group B and group C. Conclusions: Alternate-day rosuvastatin therapy showed effectiveness statistically similar to the daily dose therapy in dyslipidemic individuals. It also exhibited fewer side effects, suggesting it could be a feasible approach for managing dyslipidemia, providing a more economical and potentially safer alternative to daily administration.

Impact of pediatric continuous renal replacement therapy parameters on Meropenem, Piperacillin and tazobactam pharmacokinetics: an in vitro Model

ABSTRACT Background Limited data exist on how continuous renal replacement therapy (CRRT) affects antimicrobial dosing in pediatric patients. This study examined the impact of pediatric CRRT parameters on the pharmacokinetics (PK) of meropenem, piperacillin, and tazobactam using an in vitro CRRT model. Research design and methods An in vitro CRRT model with a pediatric ST60 circuit was used to assess antimicrobial clearance during continuous veno-venous hemodialysis (CVVHD) or hemofiltration (CVVH). Antimicrobials were administered intermittently or continuously, with samples taken pre- and post-filter, and from the effluent. The model tested two conditions: 1) off treatment (0 mL/kg/h), and 2) an elimination phase with CRRT flow rates ranging from 40 to 400 mL/kg/h. Results Clearance of meropenem, piperacillin, and tazobactam increased significantly with higher dialyzate/ultrafiltration flow rates (p < 0.001). Median clearance rates differed significantly by CRRT flow rates and modality (p < 0.001). Under CVVHD, the saturation coefficient (Sa) decreased with increasing dialyzate flow rates, while under CVVH, the sieving coefficient (Sc) remained stable regardless of ultrafiltration rates. Conclusions The clearance of low protein-binding, low molecular weight antimicrobials increases with higher CRRT effluent flow rates, with modality-specific differences in clearance dynamics.

Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: an individual participant data meta-analysis.

The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS). An individual patient data meta-analysis (IPD-MA) offers a unique opportunity to develop and validate a universal prediction model to help choose the optimal gonadotropin starting dose to minimize treatment risks without affecting efficacy. The objective of this IPD-MA is to develop and validate a gonadotropin dose-selection model to guide the choice of a gonadotropin starting dose in IVF/ICSI, with the purpose of minimizing treatment risks without compromising live birth rates. Electronic databases including MEDLINE, EMBASE, and CRSO were searched to identify eligible studies. The last search was performed on 13 July 2022. Randomized controlled trials (RCTs) were included if they compared different doses of gonadotropins in women undergoing IVF/ICSI, presented at least one type of ORT, and reported on live birth or ongoing pregnancy. Authors of eligible studies were contacted to share their individual participant data (IPD). IPD and information within publications were used to determine the risk of bias. Generalized linear mixed multilevel models were applied for predictor selection and model development. A total of 14 RCTs with data of 3455 participants were included. After extensive modeling, women aged 39 years and over were excluded, which resulted in the definitive inclusion of 2907 women. The optimal prediction model for live birth included six predictors: age, gonadotropin starting dose, body mass index, AFC, IVF/ICSI, and AMH. This model had an area under the curve (AUC) of 0.557 (95% confidence interval (CI) from 0.536 to 0.577). The clinically feasible live birth model included age, starting dose, and AMH and had an AUC of 0.554 (95% CI from 0.530 to 0.578). Two models were selected as the optimal model for combined treatment risk, as their performance was equal. One included age, starting dose, AMH, and bFSH; the other also included gonadotropin-releasing hormone (GnRH) analog. The AUCs for both models were 0.769 (95% CI from 0.729 to 0.809). The clinically feasible model for combined treatment risk included age, starting dose, AMH, and GnRH analog, and had an AUC of 0.748 (95% CI from 0.709 to 0.787). The aim of this study was to create a model including patient characteristics whereby gonadotropin starting dose was predictive of both live birth and treatment risks. The model performed poorly on predicting live birth by modifying theFSH starting dose. On the contrary, predicting treatment risks in terms of OHSS occurrence and management by modifying thegonadotropin starting dose was adequate. This dose-selection model, consisting of easily obtainable patient characteristics, aids in the choice of the optimal gonadotropin starting dose for each individual patient to lower treatment risks and potentially reduce treatment costs.

Optimizing Individualized Antimicrobial Dosing in Pediatric Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Therapeutic drug monitoring (TDM) and target concentration intervention (TCI) represent significant advancements in individualized medicine, aiming to tailor dosages based on patient-specific characteristics. These approaches account for intra- and inter-individual physiological and clinical variability, with the goal of improving target attainment and clinical remission while reducing treatment failure and adverse effects. The objective is to assess and enhance the current body of randomized controlled trials (RCTs) that have investigated alternative personalized dosing strategies, such as TDM and TCI, in terms of their efficacy and safety for individualized antimicrobial dosing in pediatric populations. Only studies that compared different dosing regimens and reported plasma concentrations were included in the analysis. Databases such as MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until January 3rd, 2024. Only published, peer-reviewed RCTs were considered for inclusion. The study focused on human subjects aged < 18 years who were receiving an antimicrobial drug. The interventions compared experimental dosing versus standard dosing with TDM or TCI. The risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials. The primary outcome was the attainment of target concentrations, while secondary outcomes included adverse effects, clinical remission, and treatment failure. Data synthesis was performed using the restricted maximum likelihood method, and the risk ratio (RR) was used as the measure of effect size. Only 11 TDM-based RCTs were included in the study [experimental vs standard doses: 592 (51.3%) patients vs 563 (48.7%) patients]. Experimental dose was significantly associated with improvement in target attainment (RR 1.2587, OR 1.0717-1.4786; p=0.0051). However, experimental antimicrobial dose optimization was non-significantly associated with a numerical decrease in treatment failure (RR 0.8966, OR 0.7749-1.0374; p=0.1424). In addition, it was not significant associated with higher adverse effects [RR 1.3408, odds ratio (OR) 0.1783-10.0825; p=0.7757] and clinical remission rates (RR 4.0589, OR 0.2494-66.0558; p=0.3250). This meta-analysis showed that only target attainment using TDM was significantly improved in pediatric patients treated with experimental doses of antimicrobials compared to standard doses. Larger TCI-focused RCTs are needed to significantly improve treatment failure, adverse effects, and clinical remission.

Predictive factors for first dose reduction and interruption of lenvatinib after beginning of the standard dose in Japanese patients with thyroid cancer.

The associations between first dose reduction or interruption by side effects and lenvatinib plasma trough concentration (C0) after administration of a starting dose of 24 mg in 70 Japanese patients with thyroid cancer were evaluated. Plasma samples were collected each week for 1 month and at the first incidence of side effects leading to dose reduction or interruption after beginning administration of 24 mg lenvatinib. The area under the receiver operating characteristic curve was 0.789 at a lenvatinib C0 threshold of 128.25 ng/mL for predicting the first dose reduction or interruption. The median time to the first dose reduction or interruption was 14.0 days in patients with a C0 of≥128.25 ng/mL and 21.0 days in those with a C0 of<128.25 ng/mL (P = 0.001). At one, two, three and four weeks respectively, the first dose reduction or interruption was associated with body weight (P = 0.034); sex (P = 0.021); sex, age, and lenvatinib C0 of≥ 128.25 ng/mL (P = 0.025, 0.024, and 0.048, respectively); and age and lenvatinib C0 of ≥ 128.25 ng/mL (each P = 0.004). On day 8 after administration of 24mg lenvatinib, lenvatinib dose may be adjusted based on the target C0 of 128.25 ng/mL to maintain a high dose intensity during this early phase; however, because persistence of a higher C0 of 128.25 ng/mL causes early dose interruption or reduction, prospective dose reduction based on the next lower target C0 for the maintenance phase may be necessary.

Photon counting CT versus energy-integrating CT: A comparative evaluation of advances in image resolution, noise, and dose efficiency.

Photon counting computed tomography (PCCT) employs direct and spectrally resolved counting of individual x-ray quanta, enhancing image quality compared to the standard energy-integrating CT (EICT). To evaluate the quantitative improvements in CT image quality metrics by comparing the first medical PCCT with a state-of-the-art EICT. The PCCT versus EICT noise improvement ratio R was derived from the quantum statistics of the measurement process and measured across the clinical x-ray flux range for both systems. Detector and system modulation transfer functions (MTFs) were obtained using tilted-slit and wire phantom measurements. Image root mean square (RMS) noise, noise power spectrum (NPS), and x-ray patient dose were compared using a CatPhan phantom at two identical clinical target resolutions. The measurement of the PCCT noise improvement ratio R showed an elimination of electronic noise and a 10% noise transfer advantage. The PCCT detector MTF exhibited 3x higher angular resolution limits in comparison to EICT and close to ideal sinc behavior due to the electromagnetic formation of pixels in the PCCT semiconductor detector. This translated to 3.5x enhancements in CT system MTF ratios at 10 LP/cm, reflecting a significant improvement in millimeter range CT imaging. Both the improved quantum detection and the system MTF ratio improvement contribute to the measured 3x enhancements in image NPS at 10 LP/cm for identical image target resolution. An improvement of up to 1.7x in RMS image noise was observed accordingly. For low and ultra-low dose imaging with image filtering, dose efficiency increased between 2x and 10x, demonstrating the PCCT's capability to advance CT ultra-low dose imaging. The direct counting detection in PCCT has been shown to significantly improve sinogram noise and detector MTF ratios compared to energy integrating EICT. The observed translations into CT system MTF, image NPS, image noise, and dose ratios reflect a paradigm shift for CT image quality and dose efficiency.

Evaluation of Response to Weight-based Dosing Strategies of Continuous, Fixed-Rate Atracurium Infusions in Critically Ill, Obese Adults With Acute Respiratory Distress Syndrome.

Fixed-rate infusions of weight-based neuromuscular blocking agents (NMBAs) were adopted during the COVID pandemic to limit caregiver exposure during titrations. Although fixed-rate infusions are supported in studies of acute respiratory distress syndrome (ARDS), the optimal scalar for weight-based NMBAs in patients with obesity remains controversial. This study sought to compare change in oxygenation using two weight-based dosing strategies for atracurium in obese patients with ARDS. Secondary outcomes included total atracurium dose, mortality, and intensive care unit (ICU) and ventilator-free days. Following an institutional practice update to use ideal body weight (IBW) for patients with obesity, we retrospectively compared adults (≥18 years) with ARDS and a body mass index (BMI) ≥ 30 kg/m2 who received atracurium (15 µg/kg/min) based on actual body weight (ABW) with those using IBW. The primary outcome was change in PaO2/FiO2 ratio (P/F) 48 hours after atracurium initiation. Analysis-of-covariance compared change in P/F between groups after adjustment for confounders. The IBW group (n = 123), compared with the ABW group (n = 133), had lower baseline P/F (85.0 [71.0, 118.3] vs 93.3 [76.0, 128.3], P = 0.025) and sequential organ failure assessment (SOFA) score (9.7 ± 2.6 vs 10.5 ± 2.6, P = 0.015), with greater use of steroids (96% vs 89%, P = 0.032) and prone positioning (72% vs 58%, P = 0.015). No difference was detected in change in P/F at 48 hours (adjusted least squares mean [95% confidence interval, CI]: 55.8 [37.0, 74.5] vs 56.9 [39.6, 74.1], P = 0.90). Atracurium doses were higher in the ABW group (97.4 mg/h [84.4, 110.3] vs 55.4 [47.2, 65.7], P < 0.001). There was no difference in hospital mortality, ICU mortality, and ICU-free days or ventilator-free days. In patients with obesity with ARDS receiving fixed-rate atracurium infusions, the change in P/F at 48 hours did not differ based on weight. Atracurium dosed on IBW may use less total drug without compromising ability to improve oxygenation. This is the first study comparing the dosing weight used for continuous infusion atracurium in hospitalized, critically ill ARDS patients with obesity. Additional studies are warranted to optimize dosing in obese patients.

Establishment of local diagnostic reference levels in terms of dose area product (DAP) in conventional radiology at the Regional Hospital Center of Souss Massa, Morocco

Introduction: The effectiveness of diagnostic reference levels (DRLs) in reducing the doses delivered to patients has been demonstrated. Establishing DRLs in terms of the dose surface product (DSP) is an essential step in the management of radiation doses in conventional radiology. Objective: This retrospective study aimed to assess local diagnostic reference levels (LDRLs) for four types of X-ray examinations in terms of DAP at the Regional Hospital Center of Souss Massa. Materials and methods: Data from 120 adult patients, 30 per location (thorax (PA), pelvis (AP), lumbar spine (AP) and abdomen (AP)) were collected. Patient parameters such as gender, age, BMI, clinical indications, and examination acquisition parameters such as kV, mAs, patient source distance (PSD), and exposure field dimensions were recorded for each patient. The calculation of DRLs is based on a statistical method known as the 75th percentile of the distribution of DAP. The data were statistically analysed by SPSS software V 21.0. Pearson’s parametric test was used to explore the relationship between the different quantitative variables. Results: The mean ESDs for the thorax (PA), lumbar spine (AP), abdomen (AP), and pelvis (AP) were 0.17, 2.55, 2.16, and 2.63 mGy, respectively. The mean DAP values for the thorax (PA), lumbar spine (AP), abdomen (AP), and pelvis (AP) were 16.53, 213.11, 230.55, and 265.19 cGy.cm2, respectively. The DRLs in terms of ESD for the thorax (PA), lumbar spine (AP), abdomen (AP), and pelvis (AP) were 0.17, 2.77, 2.64, 2.87 mGy, respectively. In terms of DAP, they were 16.58, 245, 291.83, and 300.45 cGy.cm², respectively. The results show a significant relationship between DAP and tension, charge, and ESD for all examinations. In addition, there was a significant relationship between DAP and BMI for abdomen X-ray, and no significant relationship for the three other X-ray examinations. Conclusion: It is possible to reduce the dose delivered to patients in the Regional Hospital Center of Souss Massa through the continuous training of radiology workers, implementation of a quality assurance program for equipment, and institutionalization of DRL as an approach to reducing patient doses and health service costs.

A multimodal approach to the treatment of painful diabetic neuropathy. Case report

In painful diabetic polyneuropathy (DPN), an integrated approach is effective, including kinesiotherapy, sleep hygiene, an educational program, and pharmacological agents if indicated. A case of a patient with type 1 diabetes mellitus and a painful DPN is presented. The patient received metabolic therapy for a long time, an anticonvulsant at doses that are not the safest in diabetic nephropathy. At the neurological center, the patient's dosage of analgesics was adjusted, and a complex therapy was tailored to improve comorbidities. After 3 months, during therapy, the patient reported decreased neuropathic pain in the legs, decreased hypodynamia level, partial normalization of her emotional state, and normalization of sleep quality. Risk factors for developing neuropathic pain in DPN and effective methods for its treatment as part of a multidisciplinary approach are discussed.