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Purpose: To develop anautomated treatment planning approach for whole breast irradiation with simultaneous integrated boost using an automated hybrid VMAT class solution (HVMAT). Materials and methods: Twenty-five consecutive patients with left breast cancer received 50 Gy (2 Gy/fraction) to the whole breast and an additional simultaneous 10 Gy (2.4 Gy/fraction) to the tumor cavity. Ipsilateral lung, heart, and contralateral breast were contoured as main organs-at-risk. HVMAT plans were inversely optimized by combining two open fields with aVMAT semi-arc beam. Open fields were setup to include the whole breast with a2 cm flash region and to carry 80% of beams weight. HVMAT plans were compared with three tangential techniques: conventional wedged-field tangential plans (SWF), field-in-field forward planned tangential plans (FiF), and hybrid-IMRT plans (HMRT). Dosimetric differences among the plans were evaluated using Kruskal–Wallis one-way analysis of variance. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 15002D-array. Results: No significant differences were found among the four techniques for both targets coverage. HVMAT plans showed consistently better PTVs dose contrast, conformity, and homogeneity (p < 0.001 for all metrics) and statistically significant reduction of high-dose breast irradiation. V55 and V60 decreased by 30.4, 26.1, and 20.8% (p < 0.05) and 12.3, 9.9, and 6.0% (p < 0.05) for SWF, FIF, and HMRT, respectively. Pretreatment dose verification reported agamma pass-rate greater than the acceptance threshold of 95% for all HVMAT plans. In addition, HVMAT reduced the time for full planning optimization to about 20 min. Conclusions: HVMAT plans resulted in superior target dose conformity and homogeneity compared to other tangential techniques. Due to fast planning time HVMAT can be applied for all patients, minimizing the impact on human or departmental resources.

What is known and objective To avoid misconnections between different medical devices, a unique standardized design of connectors (ENFit® ) for enteral medical devices has been developed. It was expected that the syringes with these connectors will replace the pre-existing syringes, henceforth referred to as legacy syringes. However, the changes in the connector's design led to concerns regarding dosing errors for low volume syringes (≤2 ml). Therefore, novel low dose tip (LDT) syringes were designed to address these concerns. These LDT syringes can connect with the standardized ENFit® male connectors. Only a few studies have investigated dosing errors, and findings have largely been mixed. The objective of this report was to calculate the contributions of unavoidable dosing errors for LDT syringes, compare with legacy syringes and to suggest strategies to optimize dose accuracy for enteral applications. Methods Studies performed with a limited number of syringes to date may not reflect the actual diversity of dosing error that can occur across syringe orientations, batches, manufacturers, medications, etc. A computer-aided design software SolidWorks® was used to calculate the dosing errors in 0.5 and 1.0 ml legacy syringe connectors and were compared with dosing errors in LDT syringe connectors with the same nominal volume. Influence of orientation during delivery, spillage and flushing on dosing error was also investigated. Results and discussion For 0.5 and 1.0 ml LDT syringes, in absence of medication in the moat area, the maximum dosing error will be ±5% when delivering 100% of nominal volume, which is also equal to the dosing error in 0.5 and 1.0 ml slip tip legacy syringes. However, with medication present in moat area, and with syringe reused during flushing, the LDT dosing error can range from 1% to 18% and 28% to 35% for 1.0 and 0.5 ml syringes, respectively. The corresponding dosing error for legacy syringes would be when the same syringe is used for flushing or when syringe disengages pointing vertically up. The corresponding dosing errors for legacy syringes could range from -7 to 12% and -9% to 19% for 1.0 and 0.5 ml syringes, respectively. Dosing errors for legacy and LDT syringes increase as the nominal capacity of syringe reduces, or when the dose delivered is lower than the nominal capacity of the syringe. What is new and conclusion For LDT syringes, dosing errors can be reduced by clearing the moat area of the syringe and by using a new syringe for flushing post-delivery of medication. For legacy syringes, dosing errors can be minimized by ensuring the female connector points up during disengagement from the syringe post-medication administration, and by using a new syringe for flushing.

Total body irradiation (TBI) is an external radiotherapy technique. Its aim is to deliver a therapeutic dose uniformly within ± 10% of the absorbed dose to the prescription point. In the present study, the TBI technique was implemented in anterior/posterior (AP/PA), and bilateral geometry with photons from a 6 $$\mathrm{MV}$$ and 18 $$\mathrm{MV}$$ accelerator. The TBI technique was implemented on an Alderson Rando phantom at 312 $$\mathrm{cm}$$ source surface distance. During bilateral fraction, rice bags were applied as tissue compensators. To reduce the lung’s absorbed dose to the acceptance level, in AP/PA geometry lung blocks made of Cerrobend were used. The required monitor unit (MU) for each fraction was calculated regarding depending on the prescribed dose and beam output. Gafchromic EBT3 films were used for dosimetry between the phantom layers in eight selected points. It is demonstrated that dose uniformity for AP/PA geometry with 6 $$\mathrm{MV}$$ and 18 $$\mathrm{MV}$$ photons was within ± 10%. In contrast, for the bilateral geometry the dose uniformity was not acceptable for both studied energies; However, the results for 18 $$\mathrm{MV}$$ were better than those for 6 $$\mathrm{MV}$$ . Dose accuracy for all measurements was within ± 5 of the prescribed dose. The absorbed dose to the lungs was successfully reduced using the lung blocks. By combining different therapeutic geometries and energies over six fractions, the results of uniformity and accuracy of dose delivery could be improved. It is concluded that the introduced TBI method achieved good dose accuracy and acceptable dose uniformity. Lungs absorbed dose was lower than 10 $$\mathrm{Gy}$$ using the lungs blocks. Based on these results, the TBI technique can now be implemented in radiotherapy at Tehran’s Imam Hospital. The approach developed in the present study can be used and adapted to match with the conditions at other hospitals.

Increasing the number of elderly causes an increase in health problems one of which is associated with hypertension which can cause complications and death. The purpose of this study was to determine the description and accuracy of the use of antihypertensive drugs in geriatric patients who were diagnosed with hypertension at the Tajinan Primary Health in Malang in the period January-December 2019. This study was an observational or non-experimental study conducted using retrospective medical record data. The measuring instrument used was the data collection sheet from the medical record, the Consensus for Hypertension Management 2019 to see the accuracy of indications, patient accuracy, drug accuracy, and dose accuracy. Data analysis using Correlation Test. The results of the correlation analysis showed that the resulting Standardize estimates were 0.002 (p

Pneumonia was pulmonary lung disease called parenchyma caused by microorganism, Pneumonia can be cured byantibiotic to prevent the resistantof bacteria and to improve the effective of the treatment, the right antibiotic must be determining. This research purpose is to determine the accuracy of using antibiotic in toddler patients suffering pneumonia who hospitalized in RSUD “Y” “X” City, in 2016. This is nonexperimental research. Data collected retrospectively and was analized descriptively. Samplestaken by purposive sampling method which searched the medical report of toddler patient suffer pneumonia hospitalized in RSUD “Y”X City, in 2016 which met the inclusion criteria. Reseach accuracy was analized used “Pedoman Pelayanan Medis Ikatan Dokter Anak Indonesia year 2009” and “British National Formularium for Children 2011-2012”, Such as indication accuracy, precision medicine accuracy, patient accuracy and drug dose accuracy. The result of the research was found that in 49 toddler patient suffering pneumonia, the kind of antibiotic used was cefotaxime (89,80%), Ampicillin (4,08%), combination of cefotaxime + gentamicin (4,08%) and ampicillin + gentamicin (2,04%). Evaluation of accuracy of the use antibiotic 100% right in indication, precision medicine by 93,87%,100% patient accuracy, and 10,20% drug dose accuracy.

Background: High Dose Rate (HDR) brachytherapy sources with high photon energy have been widely used in treating tumors. Dosimetric parameter of these brachytherapy sources should be determined according to the AAPM TG-43 recommendation. Gafchoromic films are reliable tools for this evaluation. Objective: The aim of this study is to evaluate and compare dose accuracy of the two-brachytherapy sources in a dedicated phantom.Material and Methods: In this analytical study, two common sources, including Cobalt and Iridium, were loaded into the dedicated phantom. The two-dimensional dose distribution around the source was calculated by TPS system for certain activities and geometries around the sources. Then, the experimental dose measured by Gafchromic film dosimetry was reported for different angles ranging from 0 to 180 degrees. Results: The difference between calculated and measured doses was less than 6 percent (-5 to +6 percent) for all of the channels and angles. These errors are smaller and mainly more than zero (Dfilm>DTPS) for angles less than 20 and larger than 110 degrees. There is no statistically significant discrepancy in dose calculation by treatment planning system. Conclusion: Although the estimated error in dose calculation is not significant, there is still an opportunity to increase the treatment precision. The correlation between the error and the angle should be considered in further plans of brachytherapy. The present study showed comparable errors compared to results of other research studies.

Aim Tablets can be manipulated in several ways to obtain a fraction as the dose—a practice frequently seen in paediatric care due to lack of suitable formulations. Splitting tablets prior to fragment dispersion in a small volume of liquid is one such method. The objective of this study was to investigate the accuracy and precision of this method. Methods Four different types of aspirin tablets (two dispersible, one conventional and one chewing) were split with a tablet splitter into half and quarter fragments. The fragments were dispersed in a medicine measure or an oral syringe. The amount recovered was determined by UHPLC analysis. Results The largest quarter fragments ranged from 26.7% to 31.5% of the full tablet weight. Dispersing the fragment in an oral syringe, the amount recovered was greater than 90.8% of the fragment manipulated for all four tablet types, when rinsing was performed. Dispersing the fragment in a medicine measure, the amounts recovered spanned from 32.9% for the conventional tablets to 98.7% for one of the dispersible tablets. Conclusion Dispersion of half or quarter tablets directly in an oral syringe, but not a medicine measure, could give satisfactory recovery from fragments of all the investigated aspirin tablets.

Tablet splitting is a common practice in clinical settings to lower doses, facilitate swallowing or save costs. Splitting devices can be used when hand splitting is difficult or painful. However, data on the accuracy of tablet splitting are limited and it presents a number of patient or formulation-related problems. Thirty nebivolol IR tablets on the Turkish market were split by hand, a tablet cutter (Rabir (R)) or a knife, and tested for weight variation, loss of mass, disintegration, and friability. The accuracy of split tablets was in the range of 75.4-121, 82.4-115, and 86.9-115% when split by hand, the cutter, and knife, respectively. No significant difference in accuracy was determined between the left and right sides split by the cutter (p = 0.222). The differences were significant for hand and knife splittings (p < 0.005). The precision was 9.02, 7.87, and 6.11% (CV%) for hand, tablet cutter, and knife, respectively. Only hand splitting failed to comply with the subdivision test of European Pharmacopoeia. The split portions met USP standards for friability (

Objectives When caring for children in a hospital setting, tablets are often manipulated at the ward to obtain the right dose. One example is manipulation of tablets containing the slightly water-soluble substance aspirin, used in paediatric care as an antiplatelet agent. The evidence base, however, for choosing certain tablet formulations and manipulation methods over others for extraction of proportions is lacking. The aim of this study was to investigate the effect of tablet formulation and manipulation technique on the dose accuracy and precision attained when dispersing different commercially available aspirin tablets and extracting a small proportion suitable for children. Methods The manipulation methods investigated simulated those observed in the paediatric clinic. Four tablet formulations—one chewable, one conventional and two dispersible—were dispersed in 10 mL water in a medicine measure. On (1) passive dispersion, (2) mixing by stirring with the syringe, or (3) stirring and pumping the dispersion in and out of the syringe, respectively, proportions (1 mL or 2 mL) were extracted and the doses recovered were determined using a validated UHPLC (ultra high-pressure liquid chromatography) method. Results Fractions from the four different dispersed aspirin tablet formulations varied from 99% to 3% of that intended with the lowest degree of mixing, and from 96% to 34% of that intended with the highest degree of mixing. Only the dispersible tablets gave average doses within 20% of the intended dose. Conclusions Fraction extraction from dispersed aspirin tablets only gave doses within 20% of intended for the dispersible tablets, and then only for some of the manipulation methods: ‘passive dispersion’ for the 75 mg dispersible tablet and ‘stirring and pumping’ for the 300 mg dispersible tablet. The tablets not intended for dispersion gave unsatisfactory results, outside 20%, regardless of manipulation method. The findings underline the importance of considering both tablet formulation and dose extraction technique when manipulations are required.

Purpose Given the large use of computed tomography (CT) worldwide, the potential harmful effects and the radiation dose delivered to the patient have become high-interest topics among the scientific community. The main objective of this work was to modify existing three-dimensional (3D) voxel phantom models to resemble real patients as much as possible, thus trying to give a contribute towards the concept of a more personalized patient dosimetry. Moreover, comparisons were made of organ dose computed in the standard reference phantom and phantoms modified to match patient body size and organ size. This study focused essentially on one of the biggest and most radiosensitive organs in the thorax, the lungs. Methods In order to accomplish this objective a FORTRAN-based program was developed, which is able to semi-automatically modify the volumetric information of organs of interest in a standard voxel phantom (Female ICRP Adult Reference). Monte Carlo (MC) PENELOPE simulation code was used to mimic CT previews and, therefore, generate 2D projections, used for visual organ matching with clinical patient CT images, and calculate organ dose in both phantoms (ICRP standard and ICRP modified). Two CT scan irradiation setups were considered, namely Fan Beam CT (FBCT) and Cone Beam CT (CBCT) geometries. Validation of the implemented MC model (voxel phantom plus X-ray sources in diagnostic energy range) was accomplished through the calculation of lung-absorbed dose per fluence conversion coefficients for the Anterior-Posterior (AP) geometry setup with subsequent comparison with ICRP 116 tabulated values. Results The main results reported that matching the voxel phantom's size and lungs provides organ dose values substantially different from the ones calculated in the ICRP reference phantom. According to the data presented in this study, organ dose can be up to 20% underestimated and 40% overestimated when compared to organ dose in the reference phantom, considering both irradiation setups. Conclusions This study demonstrates that voxel phantoms developed using single patient data could provide a better and more precise organ dose assessment by MC methods with respect to a standard phantom.

Streaking artifacts in computed tomography (CT) scans caused by metallic dental implants (MDIs) can lead to inaccuracies in dose calculations. This study quantifies and compares the effect of MDIs on dose distributions using the collapsed cone convolution superposition (CCCS) and Monte Carlo (MC) algorithms, with and without correcting for the density of the MDIs. Ion chamber measurements were taken to test the ability of the algorithms in Pinnacle3 and Monaco to calculate dose near high-Z materials. Nine previously treated patients with head and neck cancer were included in this study. The MDI and the streaking artifacts on the CT images were carefully contoured. For each patient, a plan was optimized and calculated using the Pinnacle3 treatment planning system (TPS). Two dose calculations were performed for each patient: one with overridden densities of the MDI and CT artifacts and one without overridden densities of the MDI and CT artifacts. The plans were then exported to the Monaco TPS and recalculated for the same number of monitor units (MUs) using its MC dose calculation algorithm. The changes in dose to the planning target volume (PTV) and surrounding healthy tissues were examined between all the plans using VelocityAI. For the ion chamber measurements, when correct density information was used, Monaco was within 3% of the measured values, whereas the doses calculated in Pinnacle3 varied up to 7%. The CCCS algorithm in Pinnacle3 calculated only a significant decrease in PTV coverage for 1 patient when the densities were overridden. The MC algorithm in Monaco was able to calculate a significant change in PTV coverage for five of the patients when the density was overridden. Additionally, when healthy tissues affected by streaking artifacts were assigned the correct density, cumulative (from all the fractions) point doses increased up to 46.2 Gy. Not properly accounting for MDIs can impact both the high-dose regions (PTVs) and surrounding healthy tissues. This study demonstrates that if MDIs and the artifacts are not appropriately accounted for by contouring and assigning to them the correct density, there is a potential risk of compromising the quality of the plan regarding PTV coverage and dose to healthy tissues.

Marilyn S Kwolek,1 Jon E Block2 1Private Practice, Danville, CA 94526, USA; 2Independent Clinical Consultant, San Francisco, CA 94115, USA Background: Although freehand injection of botulinum toxin remains the status quo, it is an inaccurate technique for delivering precise amounts of neurotoxin at multiple injection sites with expediency. We developed an inexpensive, ergonomic, single-use, disposable exostructure device that rapidly converts a standard syringe into a highly accurate injection instrument. Materials and methods: Based on the results of two independent injectors, we determined the comparative delivery dose accuracy, precision, and amount of product waste associated with a standard syringe using the freehand injection technique vs a prototype injection assist device. Fifteen experienced injectors were also surveyed regarding their satisfaction using the device in a controlled research setting. Results: The average percentage difference from the expected dose value was 10% or 0.0025 mL). Accuracy estimates were also superior with the device over freehand for 2- and 4-unit doses. Precision estimates favored the device for all comparisons and all dosing regimens. The magnitude of variability around the average difference ranged from 2.2 to 5.4 times worse for the freehand method compared to the device. The overall percentage of product waste was substantial with the freehand method (>10%) compared to the device (4.3%) (P=0.04) for 1-unit injections. The percentage of injections showing measurable product waste was also significantly lower with the device (78% vs 25%, P=0.01). Fourteen of 15 (93%) injectors surveyed would use the device in daily practice if it were included complimentary with the neurotoxin. Conclusion: The injection assist device offered superior accuracy and precision compared to the freehand method across the entire injection regimen. The ancillary finding of a significant reduction in product waste with the device was particularly notable. Keywords: neurotoxin, injection, syringe, accuracy

Background: The main goal of radiation therapy is to deliver the highest dose to the tumor and at the same time the lowest dose to the surrounding normal tissue. In vivo dosimetry is a quality control procedure that, instead of controlling the components separately, directly examines the dose reached to the tumor area. Objectives: In this study, the entrance, exit, and middle dose of the breast and supraclavicular area of patients with breast cancer under radiation therapy were measured and compared with calculations. Methods: In this experimental study, the entrance and exit doses of 33 patients with breast tumors treated with 6 MV and 18MV photons were measured simultaneously. The measurement was done, using p-type diodes after calibration and, then, the midpoint dose was calculated, using the transfer method and arithmetic mean method. Also, the entrance dose, exit dose, and midline dose measured with dosimeter were compared with the calculated values in the treatment planning system. Results: There was no significant difference between calculated and measured doses in the entrance, exit, and midline point in breast regions (P > 0.05), but in the supraclavicular region, a challenge was observed. The difference in entrance and midline point between calculation and measurement is not significant based on the transfer method, but there is a significant error based on the arithmetic mean method (P < 0.05). Conclusions: In vivo dosimetry by measured real given dose to the patient can perform a basic role in the quality control of the radiotherapy department. It seems in the entrance dose, the relative error is smaller but due to the smaller value of exit dose, the relative error in small values is more apparent.

Background and importance Manipulation of tablets is often necessary to achieve an appropriate dose in the paediatric ward.1 However, previous studies have shown a difference in dose accuracy obtained on manipulation for different tablets, in particular for the slightly soluble drug substance aspirin.2 Prednisolone is a very slightly soluble drug substance, and prednisolone tablets are frequently manipulated in paediatric care. Aim and objectives To investigate the dose accuracy and dose precision attained after manipulation of a commercially available prednisolone tablet, and to compare the results with those previously found for aspirin, a drug substance where solubility may similarly be challenging. Material and methods Prednisolone tablets: Prednisolon Alternova 5 mg, Alternova A/S. Instrument: UHPLC-system from Shimadzu Corp (Nexera, with prominence DAD detector). Analytical column: ACE Excel 2 μm C18-AR, 2.1 × 100 mm (Advanced Chromatography Technologies Ltd). The analytical method was validated for linearity, precision and specificity. Dosing accuracy study: six tablets were dissolved in 10 mL water. After 4 min of intermittent stirring, samples of 1 mL, a 10th of the tablet, were withdrawn. Dosing accuracy was recorded and compared with previous findings for aspirin. Results After manipulation of Prednisolon Alternova 5 mg tablets, 92.2% (85.3–95.1%) of the intended dose was retrieved. Conclusion and relevance After manipulation by dispersion and dose extraction, the prednisolone tablets were found to give doses within the limits of tablet fractions according to the European Pharmacopeia (85–115%). In contrast, conventional tablets containing aspirin (Aspirin ‘Bayer’ 500 mg), a slightly soluble drug substance, has previously been shown to have never exceeded 55% of the intended dose when a 10th of the tablet was extracted.2 This shows that knowledge about solubility is not always sufficient for estimating the suitability for manipulation of tablets. References and/or acknowledgements Bjerknes K, Boyum S, Kristensen S, et al. Manipulating tablets and capsules given to hospitalised children in Norway is common practice. Acta Paediatr 2017;106:503–8. Brustugun J, Notaker N, Paetz LH, et al. Adjusting the dose in paediatric care: Dispersing four different aspirin tablets and taking a proportion. Eur J Hosp Pharm 2019. https://doi.org/10.1136/ejhpharm-2019-001903 Conflict of interest No conflict of interest

During the last decades, inkjet printing has emerged as a novel technology and attracted the attention of the pharmaceutical industry, as a potential method for manufacturing personalized and customizable dosage forms to deliver drugs. Commonly, the desired drug is dissolved or dispersed within the ink and then dispensed in various dosage forms. Using this approach, several studies have been conducted to load hydrophilic or poorly water-soluble small molecules onto the surface of different solid substrates, including films, tablets, microneedles, and smart data-enriched edible pharmaceuticals, using two-dimensional and three-dimensional inkjet printing methods, with high dose accuracy and reproducibility. Furthermore, biological drugs, such as peptides, proteins, growth factors, and plasmids, have also been evaluated with positive results, eliciting the expected biological response; nonetheless, minor changes in the structure of these compounds with significant impaired activity cannot be dismissed. Another strategy using inkjet printing is to disperse drug-loaded nanoscale particles in the ink liquid, such as nanosuspension, nanocomplexes, or nanoparticles, which have been explored with promising results. Although these favorable outcomes, the proper selection of ink constituents and the inkjet printer, the correlation of printing cycles and effectively printed doses, the stability studies of drugs within the ink and the optimal analysis of samples before and after the printing process are the main challenges for inkjet printing, and therefore, this review analyzes these aspects to assess the body of current literature and help to guide future investigations on this field.

The objective of this study is to evaluate the dosimetric precision of the Monte Carlo (MC) algorithm to validate the Monaco® (Elekta) treatment planning system for the two radiotherapy techniques IMRT and VMAT® on the Infinity™ Elekta linear accelerator. Several irradiation plans were created on the Monaco® treatment planning system (TPS) and calculated by the integrated MC algorithm for its validation. The same plans were applied experimentally using the Matrixx Evolution 2D array with its appropriate phantom. All measurements were performed by superimposition with those calculated on the Infinity™ linear accelerator (ELEKTA). The calculated and measured dosimetric data were overlaid to make the comparison of what is realistic and what was simulated using the MyQA (IBA) software associated with the Matrixx. Good agreement was observed between calculated and measured data using 3%, 3mm distance to agreement (DTA) and low dose threshold 5% criteria. Global gamma analysis passing rates for all tests are greater than 95%. An agreement less than 2 mm is shown for open fields and homogenous dose test. However, there was increase in the agreement criteria above 3 mm for chair and pyramid test as a result of high gradient dose regions especially at the edge of target volumes. Results obtained from this study allowed, in one hand to confirm the accuracy of our MC model dose calculation with Monaco® TPS, and in the other hand, the use of the matrix detector as a standard tool for IMRT/VMAT® patient quality control.

Background: The diagnostic reference level (DRL) is measured with different methods in the common Computed tomography (CT) exams, but it has not been measured through the size-specific dose estimate (SSDE) method in Iran, yet. Objective: This study aimed to calculate the local DRL (LDRL) using the new quality control-based dose survey method (QC) and patients’ effective diameter (MQC) and compare them with a data collection method (DC) as well as local national DRLs (NDRL). Material and Methods: In this cross-sectional study, LDRL, based on the third quartile of volumetric computed tomography dose index (CTDIvol) and dose length product (DLP) values, was calculated for the four common CT examinations in four CT scan centers affiliated with Shiraz University of Medical Sciences by DC, QC and MQC methods. The CTDIvol of each patient for each CT exam calculated with three methods was compared with paired t-test. Also, the LDRL using MQC method was compared with other national DRL studies. Results: There was a significant difference between the CTDIvol values calculated with MQC and QC in all four examinations (P

Background The purpose of this study was to assess dose accuracy improvement and dosimetric impact of switching from the anisotropic analytical algorithm (AA) to the Acuros XB algorithm (AXB) when performing an accurate beam calibration in head and neck (H&N) FFF-VMAT treatments. Materials and methods Twenty H&N cancer patients treated with FFF-VMAT techniques were included. Calculations were performed with the AA and AXB algorithm (dose-to-water — AXBw– and dose-to-medium — AXBm–). An accurate beam calibration was used for AXB calculations. Dose prescription to the tumour (PTV70) and at-risk-nodal region (PTV58.1) were 70 Gy and 58.1 Gy, respectively. A PTV70_bone including bony structures in PTV70 was contoured. Dose-volume parameters were compared between the algorithms. Statistical tests were used to analyze the differences in mean values and the correlation between compliance with the D95 > 95% requirement and occurrence of local recurrence. Results AA systematically overestimated the dose compared to AXB algorithm with mean dose differences within 1.3 Gy/2%, except for the PTV70_bone (2.2 Gy/3.2%). Dose differences were significantly higher for AXBm calculations when including accurate beam calibration (maximum dose differences up to 2.8 Gy/4.1% and 4.2 Gy/6.3% for PTV70 and PTV70_bone, respectively). 80% of AA-calculated plans did not meet the D95 > 95% requirement after recalculation with AXBm and accurate beam calibration. The reduction in D95 coverage in the tumour was not clinically relevant. Conclusions Using the AXBm algorithm and carefully reviewing the beam calibration procedure in H&N FFF-VMAT treatments ensures (1) dose accuracy increase by approximately 3%; (2) a consequent dose increase in targets; and (3) a dose reporting mode that is consistent with the trend of current algorithms.

Evaluation of product viscosity, density and aeration on the dose delivery and accuracy for intravitreal injections with commonly used commercially available hypodermic 1 mL syringes. Six commercially available hypodermic 1 mL syringes with different specifications were used for the study. Syringes were filled with the test solutions with different densities and viscosities. Syringes were also subjected to shaking stress to introduce aeration in the test solutions in the presence of different surfactant concentrations with and without high antibody concentration. Target intravitreal volumes of 100 μL, 50 μL and 30 μL were tested to assess dosing accuracy in a controlled simulated administration setup using DIN ISO 11040-4 guidelines and Zwick/Roell Z010 TN instrument. With increasing product viscosity, higher volumes and hence doses were delivered especially for very low volumes like 50 μL and 30 μL. No impact of increasing product density was found on the delivered dose. The presence of surfactants or high protein concentration can lead to aeration, which also negatively affects the dose accuracy and precision. Formulation parameters like viscosity can have an impact on dose delivery using hypodermic syringes for intravitreal injections and on the resulting glide force.

Purpose: To perform a comprehensive dosimetric and clinical evaluation of the new Pinnacle Personalized automated planning system for complex head-and-neck treatments. Methods: Fifteen consecutive head-neck patients were enrolled. Radiotherapy was prescribed using VMAT with simultaneous integrated boost strategy. Personalized planning integrates the Feasibility engine able to supply an “a priori” DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually-generated (MP) and automated (AP) plans was performed using dose-volume histograms and a blinded clinical evaluation by two radiation oncologists. Planning time between MP and AP was compared. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Results: For similar targets coverage, AP plans reported less irradiation of healthy tissue, with significant dose reduction for spinal cord, brainstem and parotids. On average, the mean dose to parotids and maximal doses to spinal cord and brainstem were reduced by 13–15% (p < 0.001), 9% (p < 0.001) and 16% (p < 0.001), respectively. The integral dose was reduced by 16% (p < 0.001). The dose conformity for the three PTVs was significantly higher with AP plans (p < 0.001). The two oncologists chose AP plans in more than 80% of cases. Overall planning times were reduced to

Obtention of customized dosage forms is one of the main attractions of 3D printing in pharmaceuticals. In this sense, children are one of the groups within the population with a greater need for drug doses adapted to their requirements (age, weight, pathological state…), but most 3D printed oral dosages are solid forms and, therefore, not suitable for them. This work developed patient-tailored medicinal gummies, an alternative oral dosage form with eye-catching appearance and appropriate organoleptic characteristics. Four inks were formulated, characterised and 3D printed by means of syringe-based extrusion mechanism. Different tests were performed to ensure reproducibility of the process and validate work methodology for dosage unit fabrication applying basic manufacturing standards. Rheological test helped in evaluating inks printability. Visual characterization concluded that drugmies, apart from a high fidelity in the 3D model shape reproduction, had a bright and uniformly coloured appearance and a pleasant aroma, which made them highly appetising and attractive. The printed gummy oral dosages complied comfortably with the mass uniformity assay regardless of the formulated ink used or the 3D model selected for printing. Ranitidine hydrochloride individual contents were determined using uv-vis spectrophotometry, showing successful results both in dose accuracy, uniformity of drug content and dissolution.

Purpose To investigate, in proton therapy, whether the Gamma passing rate (GPR) is related to the patient dose error and whether MU scaling can improve dose accuracy. Methods Among 20 consecutively treated breast patients selected for analysis, two IMPT plans were retrospectively generated: (1) the pencil-beam (PB) plan and (2) the Monte Carlo (MC) plan. Patient-specific QA was performed. A 3%/3-mm Gamma analysis was conducted to compare the TPS-calculated PB algorithm dose distribution with the measured 2D dose. Dose errors were compared between the plans that passed the Gamma testing and those that failed. The MU was then scaled to obtain a better GPR. MU-scaled PB plan dose errors were compared to the original PB plan. Results Of the 20 PB plans, 8 were passed Gamma testing (G_pass_group) and 12 failed (G_fail_group). Surprisingly, the G_pass_group had a greater dose error than the G_fail_group. The median (range) of the PTV DVH RMSE and PTV ΔDmean were 1.36 (1.00–1.91) Gy vs 1.18 (1.02–1.80) Gy and 1.23 (0.92–1.71) Gy vs 1.10 (0.87–1.49) Gy for the G_pass_group and the G_fail_group, respectively. MU scaling reduced overall dose error. However, for PTV D99 and D95, MU scaling worsened some cases. Conclusion For breast IMPT, the PB plans that passed the Gamma testing did not show smaller dose errors compared to the plans that failed. For individual plans, the MU scaling technique leads to overall smaller dose errors. However, we do not suggest use of the MU scaling technique to replace the MC plans when the MC algorithm is available.

Background: A basal bolus insulin regimen requires multiple daily insulin injections, which might discourage patient adherence. As a potential solution, a mealtime insulin-delivery system—a 3-day wearable bolus-only patch—was designed to manually administer mealtime insulin discreetly by actuating buttons through clothing, without the need for multiple needle sticks. Method: Extensive functional testing of the patch included dose accuracy (from initial fill of the device to empty), pressure-vacuum leak testing, last-dose lockout and occlusion detection (safety alert features that lock the dosing buttons when no insulin is delivered), assessments of insulin drug stability, toxicological risk (including chemical testing), and system biocompatibility. Results: Dosing accuracy was 2 units ±10% (with U-100 insulin) over a range of environmental conditions, with ≥95% reliability and confidence. The fluid seal performance and the safety alert features performed with ≥95% reliability and ≥95% confidence. The system met acceptable standards for insulin (U-100 lispro and aspart) stability for its intended 3-day use, in addition to the operational requirements. The toxicological risk assessment and demonstrated biocompatibility suggested that the patch is safe for human use. Conclusions: Benchtop performance showed that the bolus-only patch is a safe, accurate, and reliable device for mealtime insulin delivery.

More than 50% of patients with type 2 diabetes mellitus are associated with hypertension. Uncontrolled blood pressure in patients with type 2 diabetes mellitus correlated with the onset of cardiovascular and cerebrovascular complications. Therefore, proper blood pressure management is needed to delay and prevent complications. Selection of appropriate antihypertensive drugs along with appropriate doses is one way to inhibit the possibility of complications. The purpose of this study is to know about the accuracy of the use of antihypertensive drugs and doses used. This research is a descriptive and observational retrospective research. The subjects of the study were 88 patients with diabetes mellitus with accompanying hypertension. Data taken include antihypertensive, antidiabetes mellitus, laboratory data. The data obtained are then analyzed descriptively using JNC edition 8 and DIH 2015. The results showed that there were 88 samples meeting the inclusion and exclusion criteria. The commonly used single antihypertensive group is Angiotensin Receptor Blocker (ARB) of 56.09%, and antihypertensive combination is Angiotensin Receptor Blocker (ARB) - Calsium Chanel Blocker (CCB) of 65.95%. Based on the results of analysis, the results obtained for the right drug and the patient is 98.86% and for the accuracy of the dose obtained 97.72%.

To date, self administrations of recombinant human follicle-stimulating hormone (rhFSH) are carried out using pen injectors with minimal dose increments of 8.33 IU or 12.5 IU (IU – international units of activity). To ensure the accuracy of dose titration and to minimize the dose adjustments during the treatment, new pen injectors are needed. Those would provide for the self administration of rhFSH in a wide range of doses and with a dose increment less than the existing fractional values. Aim: to develop a pre-filled, multi-dose pen injector for rhFSH solution with a 5 IU dose increment and a dose setting from 0 to 300 IU. Materials and methods. Dispensed volumes containing the minimal dose of 5 IU were measured gravimetrically. Results. After testing 48 pen injectors the estimated minimal dose of 5 IU (0.0083 ml of the solution) produced the following results: the mean value of the dispensed volume was 0.0081 ml, the mean deviation was ± 0.0006 ml (or ± 0.36 IU). The results are in consistence with the ISO 11608-1:2014(E) requirements of dose accuracy for the minimal dose setting in commercial injectors. Conclusion. We have developed a pen injector for rhFSH administration with a dose setting from 0 to 300 IU and with a minimal increment of dose adjustment of 5 IU. The individual approach to the dose selection/adjustment with a minimal increment of 5 IU may help achieving a highly accurate administration of rhFSH for the controlled ovarian hyperstimulation and for the induced-ovulation protocols with growth activation of 1-2 follicles.

Polymer gels are three-dimensional dosimetric tools. The purpose of the present study was to investigate the temperature dependence of polymer gels during scanning Magnetic Resonance Imaging. Prepared gels were irradiated with a 6MV X-ray beam at intensities ranging from 0 to 20 Gy in order to investigate their dose-R2 and dose-R1 responses. Irradiated gels were evaluated from 1.5-T magnetic resonance R2 and R1 images for each 5°C change in temperature from 5°C to 41°C, and then the four-field box technique irradiation plan was used to deliver a total dose of 4 Gy using the same beam weight in each direction to the prepared gels. The profile of the dose map generated from the four-field irradiated gel data at 20°C was then compared with the planned data. The dose-R2 response curve was linear up to 20 Gy at 20°C, with a slope of 1.17 Gy-1˙s-1. The slopes of the fitted curves of the dose-R2 decreased as gel temperature increased. The slopes of the dose-R1 curves were more parallel than the slopes of the dose-R2 curves between 5 and 41°C. The difference in the full width of half maximum of the gel profile data obtained using the four-field box technique at 20°C and the planned data were below 5% on average. The dose map from the irradiated gels obtained using the dose-R2 curve was the same as that from the planned data under the same temperature conditions. Measurement of difference between various temperatures is significant with dose accuracy. It is suitable to evaluate the gel dosimeter under the thermal equilibrium condition, MRI room temperature from the point of view of the stability of the irradiated gels.

Purpose/Objective(s) Biology-guided radiotherapy (BgRT), utilizes hardware that incorporates a PET detection system into a ring-gantry LINAC for real-time tracking delivery. For this study, we focus on the BgRT delivery performance in the case of static targets for dose accuracy measurement. During active beam delivery, the system operates by aiming beamlets of therapeutic radiation at malignant tumors in response to outgoing PET emissions with sub-second latency. Over a treatment fraction, these beamlets sum to the total intended dose prescribed by the physician. Physical demonstration of BgRT has not previously been reported. Here we report phantom experiments validating BgRT using static PET-avid targets of varying shapes and background PET environments. Materials/Methods An FDG-fillable insert with different shaped targets was developed to mimic different potential radiotherapy targets. Spherical and C-shaped targets were filled with 18F-flurodeoxyglucose (FDG) to represent tumors and/or organs-at-risk. The background material in the insert was either a homogenous water medium or a water filled heterogeneous medium with a Styrofoam mesh simulating lung tissue surrounding the target. Targets and OARs were filled with FDG to achieve a target/OAR: background ratio of 8:1, while the background concentration varied from 4.5-10 kBq/ml to simulate typical patient background activity concentrations. For our set-ups were investigated: Spherical target in homogenous background, spherical target in heterogeneous background, C-shaped target in homogenous background, and spherical target in homogenous background with nearby PET-avid, C-shaped OAR. For each combination, SBRT and BgRT treatment plans were created on the RefleXion treatment planning system (TPS). Next, SBRT and BgRT plans were delivered on a pre-commercial version of the RefleXion system and dosimetric accuracy was measured using the AC phantom. Gamma criteria (3%/3mm) were used to compare delivered and calculated dose. Paired Student's t-test assessed differences in SBRT and BgRT gamma pass results. Results All BgRT deliveries met 3%/3mm gamma pass criteria greater than 95% (Range, 95.2% to 98.9%). Additionally, gamma passing rates were not significantly different than the companion SBRT plans performed on the same targets (P = 0.16). Conclusion Dose accuracy results indicate that BgRT plans can be delivered accurately over a variety of test conditions (different target shapes, attenuating media and activity concentration levels) to FDG-avid targets, with performance similar to SBRT treatments.