To assess the efficacy and safety of capecitabine in treating advanced colon cancer. Patients with advanced colon cancer were randomized into three groups: control group (n = 50, daily dose 2,500 mg/m2), the medium-dose group (n = 50, daily dose 2,000 mg/m2), and the low-dose group (n = 50, daily dose 1,500 mg/m2) capecitabine for 4 cycles(12 weeks). Afterwards, the response rate, quality of life, and adverse reactions of the three groups were collected for comparison. Efficacy rates were 50%, 70%, and 72%, respectively, with the low-dose group showing the highest efficacy (χ2 = 6.424, p = 0.040); Quality of life comparison results indicated significant differences in physical function (F = 98.528, p < 0.001), role function (F = 123.418, p < 0.001), social function(F = 89.539, p < 0.001), emotional function (6 F = 77.295, p < 0.001), cognitive function (F = 83.529, p < 0.001), and overall quality of life (F = 99.528, p < 0.001) among the three groups, and the three groups returned consistent scores, with the low-dose group scoring highest. Incidence rates were 86.00%, 46.00%, 34.00%, with the control group having the highest rate (χ2 = 16.505, p < 0.001). Capecitabine at a dosage of 1,500 mg/m2 demonstrated a good therapeutic effect and improved the quality of life in patients with advanced colon cancer, with a lower incidence of adverse reactions. A prolonged treatment cycle with reduced dosage is suggested to further improve treatment outcomes and patient prognosis. Trial registration The study was registered on clicaltrials.gov \'NCT06246461\' on 30/01/2024.

In the face of increasing antimicrobial tolerance and resistance there is a global obligation to optimise oral antimicrobial dosing strategies including narrow spectrum penicillins, such as penicillin-V. We conducted a randomised, crossover study in healthy volunteers to characterise the influence of probenecid on penicillin-V pharmacokinetics and estimate the pharmacodynamics against Streptococcus pneumoniae. Twenty participants took six doses of penicillin-V (250 mg, 500 mg or 750 mg four times daily) with and without probenecid. Total and free concentrations of penicillin-V and probenecid were measured at two timepoints. A pharmacokinetic model was developed, and the probability of target attainment (PTA) calculated. The mean difference (95% CI) between penicillin-V alone and in combination with probenecid for serum total and free penicillin-V concentrations was significantly different at both timepoints (total: 45 min 4.32 (3.20-5.32) mg/L p < 0.001, 180 min 2.2 (1.58-3.25) mg/L p < 0.001; free: 45 min 1.15 (0.88-1.42) mg/L p < 0.001, 180 min 0.5 (0.35-0.76) mg/L p < 0.001). There was no difference between the timepoints in probenecid concentrations. PTA analysis shows probenecid allows a fourfold increase in MIC cover. Addition of probenecid was safe and well tolerated. The data support further research into improved dosing structures for complex outpatient therapy and might also be used to address penicillin supply shortages.

To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.

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Diagnostic reference levels (DRLs) and achievable doses (ADs) provide guidance to optimise radiation doses for patients undergoing medical imaging procedures. This multi-centre study aimed to compare institutional DRLs (IDRLs) across hospitals, propose ADs and multi-centric DRLs (MCDRLs) for four common x-ray examinations in Sri Lanka, and assess the potential for dose reduction. A prospective cross-sectional study of 894 adult patients referred for abdomen anteroposterior (AP), kidney-ureter-bladder (KUB) AP, lumbar spine AP, and lumbar spine lateral (LAT) x-ray examinations was conducted. Patient demographic information (age, sex, weight, BMI) and exposure parameters (tube voltage, tube current-exposure time product) were collected. Patient dose indicators were measured in terms of kerma-area product (PKA) using a PKAmeter. IDRLs, ADs, and MCDRLs were calculated following the International Commission on Radiological Protection guidelines, with ADs and MCDRLs defined as the 50th and 75th percentiles of the median PKAdistributions, respectively. IDRL ranges varied considerably across hospitals: 1.42-2.42 Gy cm2for abdomen AP, 1.51-2.86 Gy cm2for KUB AP, 0.83-1.65 Gy cm2for lumbar spine AP, and 1.76-4.10 Gy cm2for lumbar spine LAT. The proposed ADs were 1.82 Gy cm2(abdomen AP), 2.03 Gy cm2(KUB AP), 1.27 Gy cm2(lumbar spine AP), and 2.21 Gy cm2(lumbar spine LAT). MCDRLs were 2.24 Gy cm2(abdomen AP), 2.40 Gy cm2(KUB AP), 1.43 Gy cm2(lumbar spine AP), and 2.38 Gy cm2(lumbar spine LAT). Substantial intra- and inter-hospital variations in PKAwere observed for all four examinations. Although ADs and MCDRLs in Sri Lanka were comparable to those in the existing literature, the identified intra- and inter-hospital variations underscore the need for dose reduction without compromising diagnostic information. Hospitals with high IDRLs are recommended to review and optimise their practices. These MCDRLs serve as preliminary national DRLs, guiding dose optimisation efforts by medical professionals and policymakers.

UNASSIGNED: Diagnostic reference levels (DRLs) are an important metric in identifying abnormally high radiation doses in diagnostic examinations. National DRLs for CT colonography do not currently exist in South Africa, but there are efforts to collect data for a national DRL project.
UNASSIGNED: This study investigated radiation doses for CT colonography in adult patients at a large tertiary hospital in South Africa with the aim of setting local DRLs.
UNASSIGNED: Patient data from two CT scanners (Philips Ingenuity and Siemens Somatom go.Top) in the period March 2020 - March 2023 were obtained from the hospital\'s picture archiving and communication system (PACS) (n = 115). Analysis involved determining the median computed tomography dose index-volume (CTDIvol) and dose-length product (DLP) values. The findings were compared with DRLs established internationally.
UNASSIGNED: Ingenuity median CTDIvol was 20 mGy and DLP was 2169 mGy*cm; Somatom median CTDIvol was 6 mGy and DLP was 557 mGy*cm. Ingenuity exceeded the United Kingdom\'s (UK) recommended DRLs by 82% and 214%, respectively. Somatom median CTDIvol and DLP were 45% and 19% lower than UK NDRLs.
UNASSIGNED: Somatom\'s tin filter and other dose reduction features provided significant dose reduction. These data were used to set DRLs for CT colonography at the hospital; CTDIvol: 6 mGy and DLP: 557 mGy*cm.
UNASSIGNED: In addition to informing radiation protection practices at the level of the institution, the established local DRLs contribute towards implementing regional and national DRLs.

BACKGROUND: The adoption of size-specific dose estimate (SSDE) in clinical practice is still limited owing to the tedious and complex manual measurement of individual patient size for the clinical calculation of SSDE. Thus, the automation of SSDE is imperative. This study aims to evaluate a predictive equation for the automated calculation of SSDE.
METHODS: A user-friendly software was developed to accurately predict the individual size-specific dose estimation of paediatric patients undergoing computed tomography (CT) scans of the head, thorax, and abdomen. The software includes a calculation equation developed based on a novel SSDE prediction equation that used a population\'s pre-determined percentage difference between volume-weighted computed tomography dose index (CTDIvol) and SSDE with age. American Association of Physicists in Medicine (AAPM RPT 204) method (manual) and segmentation-based SSDE calculators (indoseCT and XXautocalc) were used to assess the proposed software predictions comparatively.
RESULTS: The results of this study show that the automated equation-based calculation of SSDE and the manual and segmentation-based calculation of SSDE are in good agreement for patients. The differences between the automated equation-based calculation of SSDE and the manual and segmentation-based calculation are less than 3%.
CONCLUSIONS: This study validated an accurate SSDE calculator that allows users to enter key input values and calculate SSDE.
CONCLUSIONS: The automated equation-based SSDE software (PESSD) seems a promising tool for estimating individualised CT doses during CT scans.

1. This study aimed to establish a population pharmacokinetic (PPK) model of mycophenolic acid (MPA), quantify the effect of clinical factors and pharmacogenomics of MPA, and optimise the dosage for adult kidney transplant recipients.2. One-hundred and four adult renal transplant patients were enrolled. The PPK model was established using the Phoenix® NMLE software and the stepwise methods were filtered for significant covariates. Monte Carlo simulations were performed to optimise the dosage regimen.3. A two-compartment model with first-order absorption and elimination (including lag time) provided a more accurate description of MPA pharmacokinetics. Serum albumin (ALB) significantly affected the central apparent clearance (CL/F), whereas post-transplant time and creatinine clearance were associated with a central apparent volume of distribution (V/F). The estimated population values obtained by the final model were 17.5 L/h and 93.97 L for CL/F and V/F, respectively. Simulation results revealed that larger mycophenolate mofetil doses are required as the ALB concentration decreases. This study established a PPK model of MPA and validated it using various methods. ALB significantly affected CL/F and recommended optimal dose strategies were given based on the final model. These results provide a reference for the personalised therapy of MPA for kidney transplant patients.

Dose optimisation is increasingly important in oncology, as exemplified by the US Food and Drug Administration\'s Project Optimus initiative, which is aligned with similar initiatives in other countries. In parallel, multiple stakeholders have raised concerns about anticancer drug prices, affordability, and access. This is of particular concern to government payers as well as patients and physicians in low- and middle-income countries. As anticancer drugs have historically been approved at the maximally tolerated dose, it is now highly relevant to question whether lower doses are equally effective and can be delivered at lower doses, resulting in less toxicity for patients, and lower costs for patients and payers. We illustrate this opportunity by discussing the combination of atezolizumab and bevacizumab, approved in multiple countries for both non-small cell lung cancer and hepatocellular cancer. Our conclusion is that the cost of this regimen can be reduced by more than 80%, an opportunity that should be considered by patients, prescribers, payers, and policymakers.

The establishment of diagnostic reference levels (DRLs) is an effective tool for optimising radiation doses delivered to patients during medical imaging procedures. This study aimed to compare the institutional DRLs (IDRLs) and propose a multi-centric diagnostic reference level (MCDRL) for chest x-ray examinations in adult patients in Sri Lanka. A prospective cross-sectional study was conducted with 1091 adult patients across six major tertiary care hospitals. Data on patient characteristics, such as age, sex, weight, and body mass index, and exposure parameters, such as tube voltage (kVp) and the product of tube current and exposure time (mAs), were collected. Patient doses were measured in terms of kerma-area product (PKA) using a PKAmeter mounted on the collimator of the x-ray tube. IDRLs were computed for each hospital according to the International Commission on Radiological Protection guidelines, and the 75th percentile PKAwas used to propose the MCDRL. The relationship between patient weight and exposure parameters was examined using Spearman\'s rank correlation to investigate the radiographic practice among hospitals. Results showed that IDRLs varied from 0.10 to 0.26 Gy cm2. The proposed MCDRL was 0.23 Gy cm2, substantially higher than the recently published DRLs from other countries. The median kVp ranged from 95 to 104, while mAs ranged from 2.5 to 5.6. Large variations in the PKAand exposure parameters were observed within and among hospitals. The elevated PKAvalues observed in this study were mostly due to the use of high mAs in clinical practice. The weak correlation observed between patient weight and exposure parameters suggests the need to standardise examination protocols concerning patient size. The observed dose variations demonstrate the need for the establishment of national DRLs. Until then, the proposed MCDRL can be considered as the benchmark dose level for chest x-ray examinations in Sri Lanka.