Individual Dose Research Articles

Comparison of two biologically effective dose calculation models applied to single fraction stereotactic radiosurgery

BackgroundRecent studies suggest strong correlations between Biologically Effective Doses (BED) and single fraction stereotactic radiosurgery treatment outcomes, as demonstrated for vestibular schwannomas (VS), arterio-venous malformations and pituitary adenomas. The BEDs calculated in these studies consider an uniform dose delivery where the spatio-temporal aspects of dose delivery were neglected. PurposeThe aim of the study is to quantify the discrepancies between the BED values calculated with a simplified model of uniform dose delivery against the more complex model that incorporates the temporo-spatial incrementation of dose delivery and the bi-exponential effect of the sub-lethal damage repair. MethodsA software tool that computes the BED distributions based on individual isocenter dose matrices extracted from the GammaPlan (Elekta) treatment planning was developed. Two cohorts 5 VS and 5 jugular foramen schwannoma cases of various tumor volumes and isocenter number were utilized to benchmark the method. Their BEDs covering 98% of tumor volumes were compared against those determined with the uniform delivery model. ResultsThe BEDs covering 98% of the tumor volumes as calculated with both models show an approximately linear dependency with the treatment time. For all studied cases, the uniform delivery model overestimates the BEDs calculated with the full spatio-temporal delivery model. This discrepancy seems to accentuate with the tumor volume and treatment complexity. ConclusionsDespite their resemblance, the BED distributions provide a plethora of BED measures more suitable to characterize clinical outcomes than the unique peripheral BED value calculated with the simplified model of uniform dose delivery.

Selecting the Best Pharmacokinetic Models for a Priori Model-Informed Precision Dosing with Model Ensembling.

When utilizing population pharmacokinetic (popPK) models for a priori dosage individualization, selecting the best model is crucial to obtain adequate doses. We developed and evaluated several model-selection and ensembling methods, using external evaluation on the basis of therapeutic drug monitoring (TDM) samples to identify the best (set of) models per patient for a priori dosage individualization. PK data and models describing both hospitalized patients (n = 134) receiving continuous vancomycin (26 models) and patients (n = 92) receiving imatinib in an outpatient setting (12 models) are included. Target attainment of four model-selection methods was compared with standard dosing: the best model based on external validation, uninformed model ensembling, model ensembling using a weighting scheme on the basis of covariate-stratified external evaluation, and model selection using covariates in decision trees that were subsequently ensembled. Overall, the use of PK models improved the proportion of patients exposed to concentrations within the therapeutic window for both cohorts. Relative improvement of proportion on target for best model, unweighted, weighted, and decision trees were - 7.0%, 2.3%, 11.4%, and 37.0% (vancomycin method-development); 23.2%, 7.9%, 15.6%, and, 77.2% (vancomycin validation); 40.7%, 50.0%, 59.5%, and 59.5% (imatinib method-development); and 19.0%, 28.5%, 38.0%, and 23.8% (imatinib validation), respectively. The best (set of) models per patient for a priori dosage individualization can be identified using a relatively small set of TDM samples as external evaluation. Adequately performing popPK models were identified while also excluding poor-performing models. Dose recommendations resulted in more patients within the therapeutic range for both vancomycin and imatinib. Prospective validation is necessary before clinical implementation.

Plasma Renin: A Useful Marker for Mineralocorticoid Adjustment in Patients With Primary Adrenal Insufficiency.

Renin is a marker of blood volume. There is no consensus on the validity of plasma renin measurement for adjusting mineralocorticoid (MC) substitution in patients with primary adrenal insufficiency (PAI). This work aimed to investigate if plasma renin could be used to adjust MC substitution in patients with PAI. A total of 150 patients with at least one measurement of plasma renin followed for PAI at 2 tertiary expert centers between 2008 and 2022 were retrospectively included. As supraphysiological hydrocortisone might have additional MC activity, we integrated the individual hydrocortisone dose to obtain the MC equivalent dose (Eq-MC). Renin less than 20 mIU/L was considered oversubstituted, renin between 20 and 60 mIU/L as correctly substituted, and renin over 60 mIU/L as undersubstituted. The mean dose of fludrocortisone was 82.3 ± 46 μg/day. Plasma renin was abnormal in 56.7% of cases (7 patients oversubstituted and 78 patients undersubstituted). Abnormalities in electrolyte levels were observed in only 12.7% of patients. Plasma renin correlated negatively with sodium (P < .01) and systolic blood pressure (P = .026), and positively with potassium (P < .01). Doses changes in Eq-MC had a statistically significant effect on renin levels (P = .0037), with an increase of MC dose correlating with a decrease in renin level and vice versa; no correlation was observed using electrolytes or blood pressure. Plasma renin correlates with electrolytes and blood pressure. While dose changes significantly alter renin levels, electrolytes and blood pressure do not, suggesting that renin may provide more information about MC replacement therapy than electrolytes and blood pressure.

Assessment of occupational dose during abdominal fluoroscopic-guided procedures in Thailand using nanoDot OSL dosimeters

Interventional radiology is one of the most widely used treatment options for abdominal abnormality. Due to new dose limitations, radiation is a hazard that needs to be considered when choosing the international treatment technique. The aim of this study was to measure the effective/equivalent doses and to investigate the associated factors correlating with the doses during Transarterial Chemoembolization (TACE) and Percutaneous Transhepatic Biliary Drainage (PTBD) for radiologists, technologists and nurses involved with the treatment. This prospective study reports occupational dose per procedure of 57 cases (TACE = 42, PTBD = 15) in a Thailand hospital spanning one year. All staff included in this study wore 30 nanoDot Optically Stimulated Luminescence Dosimeter for measuring doses at 7 bodily locations. The average dose area product and cumulative doses was 151.3 Gy·cm2, 1,185.1 mGy during TACE and 21.3 Gy·cm2, 212.2 mGy during PTBD. The radiation exposure of the radiologists was significantly higher than technologists and nurses (p-value < 0.05). The lead protection equipment was a dose-reducing factor which decreased the dose up to 93%. The present study also contributes to the establishment of an individual dose location report and identifies significant correlations between associated factors and dose values. The left hand (1.2 mSv) and the left eye (1.1 mSv) showed maximum doses during the PTBD procedure. The exceeded dose over the limitation was observed in the left eye. We concluded that the dose feedback was able to increase awareness of the occupation staff. So, dose monitoring, updating education and regular training could be applied simply and effectively to improve skills, while reducing the occupational dose.

Optimizing the individual dosing of paroxetine in major depressive disorder with therapeutic drug monitoring.

Previous studies have examined the correlation between paroxetine concentrations and therapeutic efficacy in patients diagnosed with major depressive disorder (MDD), but findings have been contradictory. This study aimed to investigate the relationships among plasma concentrations, severity of symptoms, and adverse drug reactions (ADRs) to optimize individual dosing. Eighty-seven MDD patients, after completing treatment with paroxetine, were divided into low-concentration (LC, n = 38), medium-concentration (MC, n = 27), and high-concentration (HC, n = 22) groups, based on cutoff value concentrations with the 50% response rate and the laboratory alert level from the 2017 consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. The severity of depression and anxiety was evaluated using a 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA), respectively. Dosage, plasma concentrations, scale scores, and ADRs were recorded across the three groups at different treatment stages to define the therapeutic reference range. The 4-week plasma concentration of paroxetine (65.00 ng/mL) could predict the clinical response in MDD patients at 8 weeks. Symptom relief in patients with 4-week paroxetine concentrations ranging from 65.00 to 120.00 ng/mL at 8 weeks was greater than in those with concentrations below 65.00 ng/mL, with no significant difference observed above this range. In addition, more cases of liver injury and weight gain were observed in patients with high paroxetine concentrations. Our results support that early paroxetine concentration may predict clinical efficacy and the incidence of ADRs, thus improving individual dosing regimens for MDD patients.

Risk Stratification by Combination of Heart and Lung Dose in Locally Advanced Non-Small-Cell Lung Cancer after Radiotherapy

Background/Objectives: Despite advancements in treatment for patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC), overall survival (OS) remains poor. The specific effects of varying heart and lung doses on OS in LA-NSCLC patients have not been thoroughly investigated, especially their combined impact on survival. This study aimed to examine the impact on OS of both individual and combined heart and lung doses in patients with LA-NSCLC treated with radiotherapy over a three-year follow-up period. Methods: A total of 120 patients who received definitive radiotherapy for LA-NSCLC (stage III, 92.5%) from January 2015 to January 2020 were retrospectively reviewed. The endpoint in this study was OS. Each patient was followed for a fixed period of three years. Results: Univariate Cox regression analysis showed that OS was significantly related to mean heart dose (MHD, hazard ratio [HR], 3.4 [1.8–6.3]; p &lt; 0.001), pericardium V40 (HR, 3.2 [1.7–6.0]; p &lt; 0.001), and total lung V20 (HR, 2.6 [1.4–5.0]; p = 0.003), and these were independent predictors for worse OS in multivariate analysis. Kaplan–Meier curve analysis with log-rank tests revealed that survival was significantly worse in patients with higher MHD (p &lt; 0.001), pericardium V40 (p &lt; 0.001), and total lung V20 (p = 0.002). Combining MHD and total lung V20, and pericardium V40 and total lung V20 provided enhanced risk stratification for OS (p &lt; 0.001 for both combinations). Conclusions: The combination of heart and lung doses provided enhanced and more detailed risk stratification in prediction of OS for a fixed period of three years in LA-NSCLC patients treated with radiotherapy.

Personalization of Intravaginal rings by droplet deposition modeling based 3D printing technology

Intravaginal rings (IVRs) are long-acting drug device systems designed for controlled drug release in the vagina. Commercially available IVRs employ a one-size-fits-all development approach, where all patients receive the same drug in similar doses and frequencies, allowing no space for dosage individualization for specific patients’ needs. To allow flexibility for dosage individualization, this study explores the impact of infill-density on critical characteristics of personalized IVRs, manufactured using droplet deposition modeling three-dimensional (3D) printing technology. The model drug was dispersed on the surface of thermoplastic polyurethane pellets using an oil coating method. IVR infill-density ranged from 60 to 100 %. The compatibility of the drug and matrix was assessed using thermal and spectroscopic analyses. The IVRs were evaluated for weight, porosity, surface morphology, mechanical properties, and in vitro drug release. The results demonstrated high dimensional accuracy and uniformity of 3D-printed IVRs, indicating the robustness of the printing process. Increasing infill-density resulted in greater weight, storage modulus, Young’s modulus, Shore hardness, and compression strength, while reducing the porosity of IVRs. All IVRs showed a controlled drug release pattern when tested under accelerated conditions of temperature for 25 days. Notably, greater infill-densities were associated with a decrease in the percentage of drug released. Overall, the study demonstrated that infill-density was an important parameter for personalizing the critical characteristics of the 3D-printed IVRs to fit individual patient needs.

Radiotherapy for painful shoulder syndrome: aretrospective evaluation.

We evaluated the efficacy of low-dose radiotherapy for painful shoulder syndrome from an orthopedic perspective. Patients with painful shoulder syndrome were recruited for this retrospective clinical quality assessment from January 2011 to December 2017. Patients were treated with alinear accelerator or an orthovoltage device at individual doses of 0.5-1.0 Gy and total doses of 3.0-6.0 Gy. To assess response, we used the von Pannewitz score with five levels: "worsened," "unaffected," "improved," "significantly improved," and "symptom free." "Good treatment success" was defined as "significantly improved" and "symptom free." Within-group and between-group differences were statistically evaluated. Of 236 recruited patients (150 women, 86men; mean age66.3 [range 31-96] years), 180 patients underwent radiotherapy with alinear accelerator and 56with an orthovoltage device. Fractionation was 12 × 0.5 Gy in 120 patients, 6 × 0.5 Gy in 74, and 6 × 1 Gy in 42patients. Treatments were completed in one series for 223 and in two series at least 6weeks apart for 13patients. Of the 236 patients, 163 patients (69.1%) agreed to be re-interviewed at amedian of 10.5 (range 4-60) months after radiotherapy completion. Directly after radiotherapy, 30.9% (73patients) had "good treatment success," which had increased to 55.2% (90patients) at follow-up. Protracted pain improvement with low-dose radiotherapy is possible in painful shoulder syndrome. Patients with refractory pain because of subacromial syndrome or shoulder osteoarthritis should also be evaluated for radiotherapy.

Handling delayed or missed direct oral anticoagulant doses: model-informed individual remedial dosing

AbstractNonadherence to direct oral anticoagulant (DOAC) pharmacotherapy may increase the risk of thromboembolism or bleeding, and delayed or missed doses are the most common types of nonadherence. Current recommendations from regulatory agencies or guidelines regarding this issue lack evidence and fail to consider individual differences. This study aimed to develop individual remedial dosing strategies when the dose was delayed or missed for DOACs, including rivaroxaban, apixaban, edoxaban, and dabigatran etexilate. Remedial dosing regimens based on population pharmacokinetic (PK)-pharmacodynamic (PD) modeling and simulation strategies were developed to expeditiously restore drug concentration or PD biomarkers within the therapeutic range. Population PK-PD characteristics of DOACs were retrieved from previously published literature. The effects of factors that influence PK and PD parameters were assessed for their impact on remedial dosing regimens. A web-based dashboard was established with R-shiny to recommend remedial dosing regimens based on patient traits, dosing schedules, and delay duration. Addressing delayed or missed doses relies on the delay time and specific DOACs involved. Additionally, age, body weight, renal function, and polypharmacy may marginally affect remedial strategies. The proposed remedial dosing strategies surpass current recommendations, with less deviation time beyond the therapeutic range. The online dashboard offers quick and convenient solutions for addressing missed or delayed DOACs, enabling individualized remedial dosing strategies based on patient characteristics to mitigate the risks of bleeding and thrombosis.

The Effects of Abnormal Exposure on Individual Dose Monitoring with TLD Dosimeter

Abstract Objectives: To analyze the effects of normal x-ray inspection, machine washing, and machine drying on thermoluminescent dosimeter (TLD) measurements during external individual monitoring and to provide suggestions for determining individual monitoring measurements under the mentioned abnormal situations. In this study, we focused on three abnormal situations: x-ray inspection, machine washing, and machine drying, which are common in external individual dose monitoring. We measured and compared the doses from TLD with and without 11, 23, 35, and 50 security checks. We used different radiation sources to expose the TLDs before or after machine washing with or without hot drying. The three radiation sources are natural background radiation, 137Cs γ rays, and 320 kVp x-rays. We measured 20 TLDs for each situation. The average doses for the TLDs with 11, 23, 35, 50 security checks are 27.7 μGy, 59.7 μGy, 84.1 μGy, and 121.0 μGy, respectively. We measured an average dose of 2.5 μGy per exposure. The doses showed no significant difference between different times of washing with different radiation sources, natural background radiation, 137Cs, or x-ray exposures. There was also no significant difference between the dose coming from the controlled group, drying at 60 °C and 90 °C for 1 h after exposure to 137Cs γ rays and 320 kVp x-rays. The common machine drying under the temperature of 90 °C did not affect TLD measured doses.

Radiological protection of Young Scientist and Scientific Researcher trainees in controlled areas of the Argonaut reactor installation: analytical approach

Since the increasing use of ionizing radiations in medical and industrial proceedings, recommendations and actions have been necessaries to reduce the individual radiological risks. In the Nuclear Engineering Institute (IEN), there is the Argonauta research nuclear reactor (RARG) used for producing radionuclides, neutrongraphy studies and training young scientists (YST) and scientific researchers (SRT). During their trainings, these trainees are exposed to ionizing radiations meanly during the neutrongraphyc experiments when they need to adjust neutrongraphy plates in front the J9 channel with the RARG in critical condition. At this moment, they are exposed to neutron and gamma radiations in the RARG hall. This paper evaluated the gamma and neutron expositions that YST and SRT are submitted during the neutrongraphy experiments, by using area monitors to measure the ambient dose equivalent rates in two points near to J9 channel. Considering only this experiment, there was found that the annual individual effective dose could reach up to 2.5 mSv, which is more than 150% of the annual dose to member of the public (MP), but below the annual effective dose to occupationally exposed individual (OEI) as a worker. The question is if YST and SRT should be considered an OEI or a MP. This question is answered through an analytical approach of the regulations and recommendations. The conclusion is that YST and SRT shall be controlled as OEI, but must be submitted to MP’ restriction doses.

First clinical implementation of a highly efficient daily online adapted proton therapy (DAPT) workflow.

This study presents the first clinical implementation of an efficient online daily adaptive proton therapy workflow (DAPT).&#xD;Approach: The DAPT workflow includes a pre-treatment phase, where a template and a fallback plan are optimized on the planning CT. In the online phase, the adapted plan is re-optimized on daily images from an in-room CT. Daily structures are rigidly propagated from the planning CT. Automated quality assurance (QA) involves geometric, sanity checks and an independent dose calculation from the machine files. &#xD;Differences from the template plan are analyzed field-by-field, and clinical plan is assessed by reviewing the achieved clinical goals using a traffic light protocol. If the daily adapted plan fails any QA or clinical goals, the fallback plan is used. In the offline phase the delivered dose is recalculated from log-files onto the daily CT, and a gamma analysis is performed (3%/3mm). The DAPT workflow has been applied to selected adult patients treated in rigid anatomy for the last serie of the treatment between October 2023 and April 2024.&#xD;&#xD;Main Results: DAPT treatment sessions averaged around 23 minutes [range: 15-30 min] and did not exceed the typical 30-minute time slot. Treatment adaptation, including QA and clinical plan assessment, averaged just under 7 minutes [range: 3:30-16 min] per fraction. All plans passed the online QAs steps. In the offline phase a good agreement with the log-files reconstructed dose was achieved (minimum gamma pass rate of 97.5 %). The online adapted plan was delivered for > 85% of the fractions. In 92% of total fractions, adapted plans exhibited improved individual dose metrics to the targets and/or organs at risk.&#xD;Significance: This study demonstrates the successful implementation of an online daily DAPT workflow. Notably, the duration of a DAPT session did not exceed the time slot typically allocated for non-DAPT treatment. As far as we are aware, this is a first clinical implementation of daily online adaptive proton therapy.&#xD.

Assessment of groundwater quality, irrigation suitability, and health risks from radon and heavy metals near Ilokun dumpsite, Ado-Ekiti, Nigeria

ABSTRACT Concentrations of 222Rn and other toxic metals (Ni, Cu, Fe, Cd, Zn, Pb, Cr, and Mn) were measured by alpha spectrometry using Rad7 and atomic absorption spectrophotometry, respectively, in the water samples from the Ilokun dumpsite, Ado-Ekiti, Nigeria. The physicochemical parameters of the groundwater were also assayed to determine its suitability for drinking and irrigation purposes. While the physicochemical parameters met the World Health Organization (WHO)-safety standards, Cu, Fe, Cd, Pb, Cr, and Mn exceeded permissible limits. Hazard index (HI) values for adults (8.40) and children (39.23) indicated heightened susceptibility to non-carcinogenic health risks among both age group populations. The 222Rn concentrations present in the studied samples range from 5.4 to 23.1 Bq l−1 with an average of 13.9 Bq l−1. Approximately 60% of the samples have radon concentrations above the US Environmental Protection Agency (EPA)-maximum contaminant level of 11.1 Bq l−1. The evaluated radiation doses to the stomach and respiratory tract due to radon content in the water are well below the WHO-specified individual dose criterion of 0.1 mSv year−1. This study suggests a need for groundwater resource management strategies and measures to protect human health from radiological and toxicological risks associated with groundwater consumption around the Ilokun dumpsite.

Dosage by design – 3D printing individualized cabozantinib tablets with immediate release

Production of patient-specific dosage forms is important to improve patient adherence and effectiveness while reducing the prevalence and severity of adverse effects. Due to its possibility of rapid prototyping 3D printing can be used to produce individual dosages while utilizing techniques such as hot melt extrusion to increase the bioavailability of poorly soluble drugs. In this work, Parteck MXP and Kollicoat IR were used as water-soluble polymer bases for formulation development for 3D printing of various dosages incorporating cabozantinib while enabling immediate release. The effect of tablet design and the excipients sorbitol, croscarmellose sodium, and sodium starch glycolate was investigated for this goal. A way to calculate the size of tablets for predetermined dosages is proposed to enable the printing of individual strengths from one formulation. Rheological data were collected to deepen the understanding of the role of melt viscosity in 3D printing and hot melt extrusion processes. The production of immediate-release cabozantinib tablets containing every therapeutically relevant dosage in a single unit produced by two-step 3D printing was realized.

N-of-1 trials in epilepsy: A systematic review and lessons paving the way forward.

Defined as prospective single-patient crossover studies with repeated paired cycles of active and control intervention, N-of-1 trials have gained attention as an option to obtain high-quality evidence of efficacy, particularly for patients with rare epilepsies in whom conduction of well-powered randomized controlled trials can be challenging. The objective of this systematic review is to provide an appraisal of the literature on N-of-1 trials in individuals with epilepsy. We searched PubMed and Embase on January 12, 2024, for studies meeting the following criteria: prospectively planned, within-patient, multiple-crossover design in individuals with epilepsy and outcomes related to comorbidities. Information on design, outcome measurements, intervention, and analyses was retrieved. Risk of bias assessment was performed using the Risk of Bias in N-of-1 Trials (RoBiNT) scale. We highlighted methodological aspects of the N-of-1 trials identified and discuss future recommendations. Five studies met our inclusion criteria. An additional multiple-crossover trial that evaluated treatment effects exclusively at group level was also included because of its relevance to N-of-1 study methodology. The studies enrolled individuals with focal seizures, absences or cognitive impairement and electrographic discharges. Treatments included established or investigational antiseizure medications, off-label medications, neurostimulation or lifestyle intervention. Three of the five N-of-1 trials reported on individual cases. The studies' strengths were the use of individualized treatment dosages and symptom-specific patient-reported outcomes. Limitations were related to minimal reporting of baseline characteristics and seizure burden. The trials identified by our search exemplify how the N-of-1 design can be applied to assess interventions in individuals with epilepsy-related disorders. Future N-of-1 trials of antiseizure interventions should take into account baseline seizure frequency, should apply statistical models suited to capture seizure frequency changes reliably and make predefined interim assessments. Non-seizure outcome measures evaluable over short periods should be considered. Tailored N-of-1 methodology could pave the way to evidence-based, treatment selection for patients with rare epilepsies.

Cancer Trial Eligibility and Therapy Modifications for Individuals With Duffy Null–Associated Neutrophil Count

Absolute neutrophil counts (ANCs) are used to determine cancer clinical trial (CCT) eligibility and systemic anticancer therapy (SACT) dose modifications. Duffy null-associated ANC (DANC) is a nonpathologic phenotype associated with lower ANC and most frequently seen in individuals with African and Middle Eastern ancestry. It is unclear whether CCTs exclude or SACT regimens modify doses for individuals with ANC within the DANC reference range. To investigate CCT exclusions and SACT dose modifications for ANC within the DANC reference range. This cross-sectional study of contemporary CCTs and SACT regimens included adult, interventional, phase 3 CCTs for the 5 most prevalent cancers in the US and United Kingdom (prostate, breast, melanoma, colorectal, and lung cancers) testing SACTs with start dates between November 1, 2021, and November 1, 2023, and that were registered on ClinicalTrials.gov. Preferred curative-intent SACT regimens were listed in National Comprehensive Cancer Network guidelines. Cancer clinical trial exclusions and SACT regimen modifications. Proportions of CCTs that exclude and SACT regimens that modify doses for individuals with an ANC within the DANC reference range. For CCTs, 289 of 382 trials (75.7%) were eligible, of which 221 (76.5% [95% CI, 71.1%-81.2%]) excluded patients with ANC values within the DANC reference range. Colorectal CCTs had the highest (38 of 44 [86.4% (95% CI, 72.6%-94.8%)]) and prostate CCTs had the lowest (11 of 23 [47.8% (95% CI, 26.8%-69.4%)]) proportions of exclusions. Of CCTs testing cytotoxic chemotherapy, 116 of 142 (81.7% [95% CI, 74.3%-87.7%]) had exclusions; 93 of 123 (75.6% [95% CI, 67.0%-82.9%]) CCTs testing targeted therapies alone and 12 of 24 (50.0% [95% CI, 29.1%-70.9%]) testing hormonal therapies alone had exclusions. Among the 113 US- and UK-based trials, exclusions were present in 89 (78.8% [95% CI, 70.1%-85.9%]). Of 71 SACT regimens, 38 (53.5% [95% CI, 41.3%-65.5%]) included dose modifications for ANC values within the DANC reference range. Lung cancer regimens had the highest (23 of 31 [74.2% (95% CI, 55.4%-88.1%)]) and prostate cancer had the lowest (0 of 12 [0 (95% CI, 0%-26.4%)]) proportions of modifications. Regimens including chemotherapy had modifications in 32 of 44 (72.7% [95% CI, 57.2%-85.0%]); 11 of 20 (55.0% [95% CI, 31.5%-76.9%]) of targeted therapy regimens and 0 of 16 (0% [95% CI, 0%-20.6%]) of hormonal therapy regimens had modifications. Among regimens including chemotherapy and/or targeted therapy, modifications were present in 38 of 55 (69.1% [95% CI, 49.7%-73.2%]). In this cross-sectional study, substantial proportions of CCTs excluded and SACT regimens modified doses for patients with ANCs in the DANC reference range. These practices structurally discriminate against patients of African and Middle Eastern ancestry. While determining optimal SACT dose modifications requires further study, CCT exclusion criteria should be revised.

Is personal physiology-based rapid prediction digital twin for minimal effective fentanyl dose better than standard practice: a pilot study protocol

IntroductionPatients with advanced cancer frequently suffer from chronic, severe disabling pain. Opioids such as morphine and fentanyl are commonly used to manage this pain. Transdermal drug delivery systems are important...

Short‑term effects of oxybutynin dosage in individuals with neurogenic bladder following spinal cord injury: A retrospective cohort study.

The aim of the present study was to determine the relationship between dose of oxybutynin and reduction in detrusor pressure in individuals with neurogenic bladder (NGB) secondary to spinal cord injury (SCI). The hospital-based data were examined for all individuals with NGB and SCI who were admitted for urological evaluation between January 1999 and December 2016. Patient characteristics, urodynamics and bladder management details were collected at pre-treatment and post-treatment. The primary outcome used to assess oxybutynin treatment was the change in detrusor pressure (Pdet). Analysis of covariance (ANCOVA) was used to investigate the relationship between dosage of oxybutynin and decrease in Pdet. A total of 245 participants (112 who received no medication and 133 treated with oxybutynin) were included. After controlling for confounding factors, each 1 mg increase in oxybutynin was associated with a mean decrease of 0.9 cmH2O in Pdet (95% CI, -1.4 to -0.3). Stratifying bladder management by indwelling catheter, oxybutynin at a dose of 1 mg was associated with a mean decrease in Pdet of 0.5 cmH2O (95% CI, -1.4 to 0.4) in patients with indwelling catheters and 1.0 cmH2O (95% CI, -1.7 to -0.3) in patients with clean intermittent catheterization and balanced bladder. This study provided guidance for setting the starting dose of drugs associated with response variability in NGB with SCI. Oxybutynin is deemed to be clinically effective for managing NGB in patients with SCI.

Intermittent micafungin dosing schedule in pediatric oncology patients ‐ safe for outpatient parenteral antimicrobial therapy?

IntroductionAntifungal prophylaxis is an important preventative strategy for high-risk pediatric oncology patients. When triazoles are contraindicated, micafungin is an alternative to polyenes, due to improved tolerability and limited drug-drug interactions. An intermittent dosing schedule is advantageous for outpatient parenteral antimicrobial therapy (OPAT), but studies assessing safety in pediatric patients are limited. MethodsThis single-centre, retrospective, observational study compared the safety and tolerability of daily (1 mg/kg) and intermittent (3 mg/kg) dosing of amphotericin B liposomal (AmB) and micafungin in children under 18 years, with high-risk leukemia. ResultsOf 51 patients, with 76 individual dosing schedules, hepatoxicity and nephrotoxicity were comparable across all four dosing schedules. Severity of hypokalemia was significantly higher amongst patients receiving AmB (p = 0.041), with higher rates of intravenous electrolyte supplementation required. Infusion-related reactions occurred only in the AmB group (22 %). Intermittent administration and dosing of micafungin was well tolerated, with similar effects on liver function and reduced rates of hypokalemia. ConclusionThis study supports the positive safety profile of intermittent micafungin compared with AmB and describes successful OPAT implementation. Prospective studies assessing efficacy are needed to validate these findings.

Lisdexamfetamine's Efficacy in Treating Attention Deficit Hyperactivity Disorder (ADHD): A Meta-Analysis and Review.

Lisdexamfetamine dimesylate, a prodrug stimulant, appears to effectively treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adults. However, an analysis of the treatment effects of the two subscales (inattentiveness and hyperactivity) within the ADHD Rating Scale-IV (ADHD-RS-IV) has not yet been done to determine if clinical significance may be attributed to either one. Nor has there been a meta-analysis of the individual doses of lisdexamfetamine dimesylate. The current meta-analysis utilizes MEDLINE, Embase, Cochrane, PubMed, and clinicaltrials.gov to identify peer-reviewed studies. Selected studies were eligible if they met the following criteria: English language, randomized-controlled trials, and utilized the ADHD-RS-IV scale to assess the efficacy of lisdexamfetamine on treating ADHD in either children or adults. The primary studies utilized were published between January 2007 and April 2024. Many of these studies calculate effect sizes based on several dosages pooled together rather than by individual dosages. We conducted a random-effects meta-analysis to estimate the effect sizes for these pooled dosages on the full ADHD-RS-IV scale and its subscales, as well as to calculate effect sizes on the same scales based on the individual dosages. Our main outcome measures are the ADHD-RS-IV scale and its subscales in individual doses and pooled results in both children and adults. Adverse events during treatment were also analyzed based on stratified dosages. Eleven publications met our inclusion criteria. The analyses indicate that compared to placebo, lisdexamfetamine effectively alleviates the symptoms outlined by the ADHD-RS-IV. Moreover, there are no differences in the individual subscales or in the safety profile. Lisdexamfetamine demonstrates efficacy in treating the symptoms of ADHD, but we report that differing dosages did not yield significant differences in ADHD symptom management.