An Automated, Dynamic Radiation Oncology Prescription Checking System.

PURPOSE: Despite serving as a critical communication tool, radiation oncology prescriptions are entered manually and prone to error. An automated prescription checking system was developed and implemented to help address this problem. METHODS AND MATERIALS: Rules defining clinically appropriate prescriptions were generated, examining specific types of errors: (1) unapproved dose per fraction for a given disease site; (2) dose per fraction too large for nonstereotactic treatment technique; and (3) dose per fraction too low. With a goal of catching errors as upstream as possible to minimize their propagation, a report was created and ran every 30 minutes to check all newly written or approved prescriptions against the 3 rules. When a prescription violated these rules, an automated email was immediately sent to the prescriber alerting them of the potential error. System performance was continuously monitored and the criteria triggering an alert adjusted to balance error detection against false positives. Alerts leading to prescription amendment were considered true errors. RESULTS: From June 2021 to November 2022, the system checked 24,047 prescriptions. A total of 241 email alerts were triggered, for an average alert rate of 1%. Of the 241 alerts, 198 (82.2%) were unapproved doses per fraction for the disease site, 14 (5.8%) were doses per fraction that were too low, and 29 (12%) were doses too large for nonstereotactic treatment technique. Thirty-one percent of alerts led to a change of prescription, suggesting they were true errors. The baseline rate of erroneous prescription entry was 0.3%. A regression model showed that trainee prescription entry and dose per fraction <150 cGy were significantly associated with true errors. CONCLUSIONS: Given the significant consequences of erroneous prescription entry, which ranged from wasted resources and treatment delays to potentially serious misadministration, there is significant value in implementing automated prescription checking systems in radiation oncology clinics.

External validation of Cardiac disease, Hypertension, and Logarithmic Left anterior descending coronary artery radiation dose (CHyLL) for predicting major adverse cardiac events after lung cancer radiotherapy.

Background and purpose: Major adverse cardiac events(MACE) are prevalent in patients with locally advanced-non-small cell lung cancer(LA-NSCLC) following radiotherapy(RT). The CHyLL model, incorporating coronary heart disease(CHD),Hypertension(HTN),Logarithmic LADV15 was developed and internally-validated to predict MACE among LA-NSCLC patients. We sought to externally validate CHyLL to predict MACE in an independent LA-NSCLC cohort. Patients and methods: Patients with LA-NSCLC treated with RT were included. CHyLL score was calculated:5.51CHD + 1.28HTN + 1.48ln(LADV15 + 1)-1.36CHD*ln(LADV15 + 1). CHyLL performance in predicting MACE was assessed and compared to mean heart dose(MHD) using Cox-proportional hazard(PH) analyses and Harrel's concordance(C)-indices. MACE and overall survival(OS) among low-vs high-risk groups(CHyLL < 5 vs ≥ 5) were compared. Results: In the external validation cohort(N = 102), the median age was 71 years and 55% were females. Most(n = 74,73%), had clinical Stage III disease and 35(34%) underwent surgery. CHyLL demonstrated good MACE prediction with C-index of 0.73(95% Confidence Interval(CI):0.58-0.89), while MHD did not (C-index = 0.46 (95% CI:0.30-0.62)). Per CHyLL, 32(31%) and 70(69%) patients were considered low-and high-risk for MACE, respectively. CHyLL consistently identified lower MACE rates in the low-vs high-risk group(log-rank p = 0.108):0 vs 8%(12 months),5 vs 16%(24 months),5 vs 16%(36 months),and 5 vs 19%(48 months) post-RT. In the pooled internal and external validation cohort(N = 303), MACE rates in low-vs high-risk groups were statistically significantly different(log-rank p = 0.01):1 vs 6%(12 months),3 vs 12%(24 months),6 vs 19%(36 months),and 6 vs 21%(48 months). Conclusions: CHyLL was externally validated and superior to MHD in predicting MACE. CHyLL has the potential to identify high-risk patients who may benefit from cardio-oncology optimization and to estimate personalized LADV15 constraints based on cardiac risk factors and acceptable MACE thresholds.

Hidden in Plain Sight: Clinical Informaticians are the Oncology Subspecialists You Did Not Know You Needed.

Clinical informatics is a young, diverse and rapidly growing field. We asked eight clinical informaticians from a variety of oncology specialties, training pathways and careers for personal narratives to illustrate the wide spectrum of clinical informatics careers. Primary clinical specialties included radiation oncology, medical/haematology oncology and palliative care. Training pathways included fellowship, non-fellowship formal training and informal training. Careers included clinical care, research, operations and industry. We summarised common themes and advice for trainees. We hope to raise awareness of clinical informatics among trainees and oncologists to reveal new career opportunities and to avoid inadvertently taking clinical informatics and informaticians for granted.

Posterior urethral valves: comparison of clinical outcomes between postnatal and antenatal cohorts.

BACKGROUND: Posterior urethral valves (PUVs) constitute the most common infravesical urinary obstruction in boys and are often accompanied by severe consequences to the lower and upper urinary tract. Currently, about two-thirds of diagnosis of PUVs has been suspected by prenatal ultrasonography findings. The aim of this study was to compare long-term clinical outcomes in two groups of patients with PUVs, with antenatal vs. postnatal diagnosis. STUDY DESIGN: This was a retrospective cohort study of 173 patients with PUVs systematically followed up in a tertiary center. Median follow-up time was 66.5 months (interquartile range [IQ], 11.4-147.9 months) for those patients who survived neonatal period. Seventy-nine (45.6%) patients were followed up for more than 5 years and 55 (32%) for more than 10 years. For analysis, the cohort was stratified into two groups according to the clinical presentation (prenatal vs. postnatal). The events of interest were urinary tract infection (UTI), surgical interventions, proteinuria, hypertension, chronic kidney disease (CKD), and death. Survival analyses were performed to evaluate time until occurrence of the events. RESULTS: Sixty-two patients (35.8%) were diagnosed by fetal sonography. Patients of postnatal group presented a higher incidence rate of UTI episodes (6.5, 95% confidence interval [CI], 4.9-8.3) than antenatal group (1.2, 95% CI, 0.4-2.7) (P < 0.001). Thirty-six patients (21%) presented hypertension, and 77 (44.5%) had persistent mild proteinuria. There was no significant difference in the estimated incidence of hypertension (P = 0.28) and proteinuria (P = 0.78) between antenatal and postnatal groups. The cumulative incidence of CKD stage ≥3 was estimated to be about 37% at 10 years of age, and 56% at 18 years of age. By survival analysis, there was no significant difference in the estimated incidence of CKD stage ≥3 (log-rank = 0.32, P = 0.57) and CKD stage 5 (log-rank = 1.08, P = 0.28, Figure) between antenatal and postnatal groups. Of 173 patients included in the analysis, 13 (7.5%) died during follow-up with a median age of 2.6 months (IQ, 15 days-62 months). Survival analyses have not shown any significant difference in the estimated incidence of death between antenatal and postnatal groups (log-rank = 1.38, P = 0.24). CONCLUSION: The study findings did not corroborate the initial hypothesis that the rates of renal function declining in patients with PUVs would be attenuated by an early diagnosis and intervention after antenatal diagnosis.

Intracellular distribution and stability of a luminescent rhenium(i) tricarbonyl tetrazolato complex using epifluorescence microscopy in conjunction with X-ray fluorescence imaging.

Optical epifluorescence microscopy was used in conjunction with X-ray fluorescence imaging to monitor the stability and intracellular distribution of the luminescent rhenium(i) complex fac-[Re(CO)3(phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence imaging techniques. X-ray fluorescence also showed that the rhenium complex disrupted the homeostasis of some biologically relevant elements, such as chlorine, potassium and zinc.

The Bionanoprobe: hard X-ray fluorescence nanoprobe with cryogenic capabilities.

Hard X-ray fluorescence microscopy is one of the most sensitive techniques for performing trace elemental analysis of biological samples such as whole cells and tissues. Conventional sample preparation methods usually involve dehydration, which removes cellular water and may consequently cause structural collapse, or invasive processes such as embedding. Radiation-induced artifacts may also become an issue, particularly as the spatial resolution increases beyond the sub-micrometer scale. To allow imaging under hydrated conditions, close to the `natural state', as well as to reduce structural radiation damage, the Bionanoprobe (BNP) has been developed, a hard X-ray fluorescence nanoprobe with cryogenic sample environment and cryo transfer capabilities, dedicated to studying trace elements in frozen-hydrated biological systems. The BNP is installed at an undulator beamline at sector 21 of the Advanced Photon Source. It provides a spatial resolution of 30 nm for two-dimensional fluorescence imaging. In this first demonstration the instrument design and motion control principles are described, the instrument performance is quantified, and the first results obtained with the BNP on frozen-hydrated whole cells are reported.

TU-E-BRB-02: A Decision Support Tool for SBRT Planning Using a Searchable DVH Database.

PURPOSE: Develop a decision support tool that aids dosimetrists, physicians, and physicists in assessing and improving plan quality through comparison to plans previously used in similar clinical situations. METHODS: Software was developed to capture and store DVHs and other clinically relevant treatment plan characteristics in a database. In addition to the plan DVH, the database contains a total of 24 plan characteristics including fractionation, prescribed dose, treatment volume, prior surgery, tumor position, and smoking history. DVH and other plan data was captured from the treatment planning system via exported dicom RT files. Structures in the plan were automatically matched by name to a list of standard structures using a system of regular expressions. Additional fields were entered manually using a simple java interface. As a support tool, a plan under development can be quickly compared to similar plans in the database based on selected plan characteristics. A plot displaying the current and historical DVHs provides an easy visual comparison. Our interface also provides statistics for comparison for each dose/volume level such as average, minimum, maximum and standard deviation. RESULTS: DVHs from 111 lung SBRT plans treated from 2009-2011 were imported in accordance with an approved IRB protocol. As an example of data comparisons that can be easily performed to guide plan evaluation, we examined plans prescribing 5400cGy in 3 fractions and found that tumors >7.5cc (n=34) had an average PTV coverage of 94.2% (range: 73.5-95.0%), and tumors =7.5cc (n=35) had an average PTV coverage of 94.9% (range: 81.6-99.6%). CONCLUSION: A searchable DVH database was constructed to provide planners, physicists, and physicians with a straightforward means of comparing plans against historic distributions of DVHs. In the future, outcome data will be included in the database to strengthen its functionality as a decision support and research tool.

SU-E-J-126: Generation of Fluoroscopic 3D Images Using Single X-Ray Projections on Realistic Modified XCAT Phantom Data.

PURPOSE: To simulate the process of generating fluoroscopic 3D treatment images from 4DCT and measured 2D x-ray projections using a realistic modified XCAT phantom based on measured patient 3D tumor trajectories. METHODS: First, the existing XCAT phantom is adapted to incorporate measured patient lung tumor trajectories. Realistic diaphragm and chest wall motion are automatically generated based on input tumor motion and position, producing synchronized, realistic motion in the phantom. Based on 4DCT generated with the XCAT phantom, we derive patient-specific motion models that are used to generate 3D fluoroscopic images. Patient-specific models are created in two steps: first, the displacement vector fields (DVFs) are obtained through deformable image registration of each phase of 4DCT with respect to a reference image (typically peak-exhale). Each phase is registered to the reference image to obtain (n-1) DVFs. Second, the most salient characteristics in the DVFs are captured in a compact representation through principal component analysis (PCA). Since PCA is a linear decomposition method, all the DVFs can be represented as linear combinations of eigenvectors. Fluoroscopic 3D images are obtained using the projection image to determine optimal weights for the eigenvectors. These weights are determined through iterative optimization of a cost function relating the projection image to the 3D image via the PCA lung motion model and a projection operator. Constructing fluoroscopic 3D images is thus reduced to finding optimal weights for the eigenvectors. RESULTS: Fluoroscopic 3D treatment images were generated using the modified XCAT phantom. The average relative error of the reconstructed image over 30 sec is 0.0457 HU and the standard deviation is 0.0063. CONCLUSIONS: The XCAT phantom was modified to produce realistic images by incorporating patient tumor trajectories. The modified XCAT phantom can be used to simulate the process of generating fluoroscopic 3D treatment images from 4DCT and 2D x-ray projections.

Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older.

Randomized trials of chemoradiation for esophageal cancer have included very few patients age > or = 75. In this retrospective study, we describe the outcomes and toxicity of full-dose chemoradiation in elderly patients with esophageal cancer. Patients, age > or = 75, treated with full-dose chemoradiation for esophageal carcinoma from 2002 to 2008 were retrospectively reviewed. Thirty-four patients were identified with a median age of 79.5 (range 75-89). The median Eastern Cooperative Oncology Group performance status was 1 (range 0-3) and the median Adult Comorbidity Evaluation-27 score was 1 (range 0-3). Twenty-eight patients received definitive and six received neoadjuvant chemoradiation. The median radiation dose delivered was 50.4 Gray (range 3.6-68.4 Gray). Platinum-based chemotherapy was used in 79.4% of patients. Fifty percent of the patients completed all planned radiation therapy (RT) and chemotherapy; 85.3% completed RT. Acute toxicity > or = grade 4 occurred in 38.2% of patients, and 70.6% of the patients required hospitalization, emergency department visit, and/or RT break. Median follow-up was 14.5 months among 7 survivors, and median survival was 12.0 months (95% confidence interval [CI]: 9.7 to 24.1 months). The actuarial overall survival at 2 years was 29.7% (95% CI: 16.6 to 52.6%). There were four treatment-related deaths. The median time to any recurrence was 10.4 months. Nineteen patients had a local and/or distant recurrence. In conclusion, elderly patients experienced substantial morbidity from chemoradiation, and long-term survival was low. Future efforts to improve treatment tolerability in the elderly are needed.

Antimicrobial stewardship program directed at broad-spectrum intravenous antibiotics prescription in a tertiary hospital.

The antimicrobial stewardship program (ASP) is a major strategy to combat antimicrobial resistance and to limit its expenditure. We have improved on our existing ASP to implement a sustainable and cost-effective two-stage immediate concurrent feedback (ICF) model, in which the antimicrobial prescription is audited by two part-time infection control nurses at the first stage, followed by "physician ICF" at the second stage. In January 2005, an ASP focused on broad-spectrum intravenous antibiotics was implemented. All in-patients, except from the intensive care, bone marrow transplantation, liver transplantation, pediatric, and private units, being treated with broad-spectrum intravenous antibiotics were included. The compliance to ICF and "physician ICF", antibiotics usage density measured by expenditure and defined daily doses (DDD) were recorded and analyzed before and after the ASP. The overall conformance rate to antibiotic prescription guidelines was 79.4%, while the conformance to ICF was 83.8%. Antibiotics consumption reduced from 73.06 (baseline, year 2004) to 64.01 (year 2007) per 1,000 patient bed-day-occupancy. Our model can be easily applied even in the clinical setting of limited resources.

[Incidence of Neisseria gonorrhoeae infections in Belgium: trends 2000-2006]. / Incidence des infections à Neisseria gonorrhoeae en Belgique: tendances 2000-2006.

In Belgium, three registration systems collect epidemiological information on N. gonorrhoeae infections. The descriptive analysis of the data presented in this article allows describing the epidemiology of N. gonorrhoeae infections in Belgium in terms of trends in time, describing the characteristics of the patients, and providing information on resistance to antibiotics. The results on the incidence of N. gonorrhoeae infections show an important increase since the year 2000, and this increase is even more pronounced between 2005 and 2006. The majority of the patients reside in big cities, mainly in the district of Antwerp and in the Brussels-Capital region. Among the N. gonorrhoeae specimens that were sent to the reference laboratory, the proportion of specimens resistant to ciprofloxacine increases each year; this proportion reaches 61.4% in 2006. The increase in the incidence of N. gonorrhoeae infections and in antimicrobial resistance is also observed in other European countries. The increase in incidence may be partly related to the important increase of resistance to ciprofloxacine. It is very important to continue the surveillance of antimicrobial resistance, to adapt treatment in function of the recent evolutions and to inform physicians at a regular basis. The results show that homo- and bisexual men are most at risk for N. gonorrhoeae infections. The prevention campaigns for sexually transmitted infections and screening policy have to be reinforced, particularly among homo- and bisexual men.

Progress in understanding the immunopathogenesis of psoriasis.

This review emphasizes how translation from bench research to clinical knowledge and vice versa has resulted in considerable progress in understanding the immunopathogenesis of psoriasis. First, the journey in understanding the pathogenic mechanisms behind psoriasis is described. The roles of different components of the adaptive and innate immune systems involved in driving the inflammatory response are explained. Discovery of new immune pathways i.e. the IL23/Th17 axis and its subsequent impact on the development of novel biological therapies is highlighted. Identification of potential targets warranting further research for future therapeutic development are also discussed.

Compliance and immunogenicity of two hepatitis B vaccination schedules in sex workers in Belgium.

OBJECTIVES: To compare the coverage for the third dose and the compliance to two hepatitis B vaccination schedules: 0,1,4 versus 0,1,6 months, in commercial sex workers (CSW) in Belgium; to compare the immunogenicity of the actually administered schedules. METHODS: In seven health centres in Belgium, hepatitis B vaccination was offered free of charge to CSW. In a randomised, prospective study a commercialised hepatitis B vaccine (Engerix-B 20mcgr) was offered according to one of both schedules. After complete vaccination, bleeding was performed to assess immunogenicity. RESULTS: Between June 2003 and September 2004, 615 non-immune CSW were enrolled, of whom 52% in the 0,1,4 month schedule (n=322). Coverage of the third dose was 57% overall, 59% (0,1,4) and 54% (0,1,6), respectively. Age, the health centre and drug use significantly influenced the compliance and the coverage of dose 3, whereas the planned vaccination did not. When comparing the immunogenicity results as a function of the actually administered vaccination schedule, immune responses did not significantly differ between CSW receiving the third dose 4-6 months and those receiving it at least 6 months after the first dose. In total, 19 persons (8%) were not protected after a full vaccination course (anti-HBs <10IU/L). Two health centres measured markedly lower anti-HBs levels. CONCLUSIONS: In this highly mobile at-risk population, a 0,1,4 month schedule is more easy to offer and confers equal protection within a shorter period of time. We therefore propose this 0,1,4 month schedule to vaccinate CSW in the future.

Myostatin and insulin-like growth factors in uremic sarcopenia: the yin and yang in muscle mass regulation.

Myostatin and the insulin-like growth factors (IGF-I and -II) play inhibitory and stimulatory roles, respectively, in the development and regulation of skeletal muscle mass. The findings of Sun et al. in this issue shed light on the potential regulation and actions of this yin-and-yang system in uremic sarcopenia and the salutary effects of exercise.

An unusual patient with Rothmund-Thomson syndrome, porokeratosis and bilateral iris dysgenesis.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis characterized by poikiloderma and the variable presence of other features including skeletal and ocular abnormalities, ectodermal defects, and susceptibility to certain malignancies. We report a 40-year-old woman with known RTS who developed porokeratoses on her limbs in adulthood, an association that has not previously been reported. In addition, she had bilateral iris dysgenesis, which has only been described once before in RTS.

Leptin and inflammation-associated cachexia in chronic kidney disease.

Leptin is an adipocyte-derived hormone that acts as a major regulator of food intake and energy homeostasis. It circulates both as a free and as a protein-bound entity. Leptin is released into the blood in proportion to the amount of body fat and exerts sustained inhibitory effects on food intake while increasing energy expenditure. The leptin receptor belongs to the class I cytokine receptor superfamily and possesses strong homology to the signal-transducing subunits of the IL-6 receptor. The hypothalamic melanocortin system, and specifically the melanocortin-4 receptor (MC-4R), is critical in mediating leptin's effect on appetite and metabolism. Serum leptin concentrations are elevated in patients with chronic kidney disease (CKD) and correlate with C-reactive protein levels suggesting that inflammation is an important factor that contributes to hyperleptinemia in CKD. Hyperleptinemia may be important in the pathogenesis of inflammation-associated cachexia in CKD. We showed that experimental uremic cachexia was attenuated in db/db mice, a model of leptin receptor deficiency. Nephrectomy in these animals did not result in any change in weight gain, body composition, resting metabolic rate, and efficiency of food consumption. Furthermore, experimental uremic cachexia could be ameliorated by blocking leptin signaling through the hypothalamic MC-4R. MC-4R knockout mice or mice administered the MC-4R and MC-3R antagonist, agouti-related peptide, resisted uremia-induced loss of lean body mass and maintained normal basal metabolic rates. Thus, melanocortin receptor antagonism may provide a novel therapeutic strategy for inflammation-associated cachexia in CKD.