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• We carefully identified possible handling procedures for CSTDs that may impact dose accuracy when transferring small volumes during dose preparation, and systematically evaluated these different handling procedures for all steps of a complex dose preparation scheme common with first-in-human drug product configurations. • We show that the risk of underdosing and overdosing with non-ideal handling procedures depends not only on CSTD component hold-up volumes, but on drug product reconstitution volume and withdrawal/transfer volume, and that the impact can be predicted theoretically when these volumes are known. • We show that dose accuracy can be achieved in all situations using multiple syringe units (syringe adapter + syringe) and flushing of vial/bag adapters. However, clear instructions for each step are necessary, because a seemingly inconsequential difference in handling procedure can mean the difference between accurate dosing and severe under- or over-dosing. • We explore potential downsides of the identified mitigation techniques through assessment of particle and protein aggregate formation from silicone oil leaching and mechanical or interfacial stress. Many challenges have been identified for ensuring compatibility of closed system transfer devices (CSTDs) with biologic drug products. One challenge is large hold-up volumes (HUVs) of CSTD components, which can be especially problematic with early-stage biologics when low transfer volumes smaller than the nominal fill volume may be used to achieve a wide range of doses with a single drug product configuration. Here, we identified possible CSTD handling techniques during dose preparation of a drug product requiring small volume transfers during reconstitution, intermediate dilution, and dilution in an IV bag, and systematically evaluated the impact of these handling procedures on the ability to deliver an accurate dose to the next step. We show that small changes to CSTD procedures can have a major impact on dose accuracy, depending on both CSTD HUVs and drug product-specific transfer volumes. We demonstrate that it is possible to craft CSTD instructions for use to mitigate these issues, and that the dose accuracy for specific drug product/CSTD combinations can be estimated using theoretical equations. Finally, we explored potential downsides of these mitigations. Our results emphasize key factors for consideration by both drug and CSTD manufacturers when assessing compatibility and providing CSTD instructions for use with biologics requiring low transfer volumes during dose preparation. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to establish criteria for convolution dose calculations and an efficient procedure to include the heterogeneity effects in GammaKnife radiosurgery (GKRS) treatment plans. Methods and materials: We analyzed 114 GKRS cases of various disease types, tumor locations, sizes, the number of fractions, and prescription doses. There was a total of 205 tumors. CT scans were performed in addition to routine MRI scans for all treatments. All treatment plans were created using the TMR10 algorithm (TMR10). We repeated the dose calculations for this study with the convolution algorithm (Conv). We calculated the ratios between Conv and TMR10 of the treatment volume (TxtVol), the volume covered by half of the prescription dose (TxtVol2), the minimum, maximum, and mean doses in the tumor (minDose, maxDose, and meanDose), and the volume of tumor covered by the prescription isodose (covVol). We then categorized those quantities for locations of tumors represented by the shortest distance of the skull surface from the tumor center (distC) and the tumor edge (distE). Results: All six ratios increased with increasing distC and distE. For example, the median minDose ratio increased from 0.885 to 0.933 as distE increased. There was a statistically significant difference in the minDose ratio between tumors of distE < 2 cm and distE ≥ 2 cm. On the other hand, the median maxDose ratio was about 0.933 [0.928-0.939], being almost independent of distE. This suggested a 6.1% overestimation of the delivered dose with TMR10. Conclusions: The heterogeneity effects must be considered for the volume dose calculations by applying the convolution algorithm when the distance of the skull surface from the closest point of the tumor is less than 2 cm to achieve less than 3% accuracy. [ABSTRACT FROM AUTHOR]

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 (Rabır®) 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

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 (Rabır®) 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 (<1%). Splitting decreased the disintegration time (4.5 vs. 2.2 min). Overall, the accuracy of the tablet cutter was more favorable than hand splitting and knife. The study demonstrated that the splitting technique may result in inaccurate dosing and significant drug fluctuations for nebivolol tablets. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of intra-fractional motion on dose distribution in patients treated with intensity-modulated radiotherapy (IMRT) for lung cancer. Materials and methods: Twenty patients who had undergone IMRT for non-small cell lung cancer were selected for this retrospective study. For each patient, a four-dimensional computed tomography (CT) image set was acquired and clinical treatment plans were developed using the average CT. Dose distributions were then recalculated for each of the 10 phases of respiratory cycle and combined using deformable image registration to produce cumulative dose distributions that were compared with the clinical treatment plans. Results: Intra-fractional motion reduced planning target volume (PTV) coverage in all patients. The median reduction of PTV covered by the prescription isodose was 3·4%; D98 was reduced by 3·1 Gy. Changes in the mean lung dose were within ±0·7 Gy. V20 for the lung increased in most patients; the median increase was 1·6%. The dose to the spinal cord was unaffected by intra-fractional motion. The dose to the heart was slightly reduced in most patients. The median reduction in the mean heart dose was 0·22 Gy, and V30 was reduced by 2·5%. The maximum dose to the oesophagus was also reduced in most patients, by 0·74 Gy, whereas V50 did not change significantly. The median number of points in which dose differences exceeded 3%/3 mm was 6·2%. Findings: Intra-fractional anatomical changes reduce PTV coverage compared to the coverage predicted by clinical treatment planning systems that use the average CT for dose calculation. Doses to organs at risk were mostly over-predicted. [ABSTRACT FROM AUTHOR]

Background: Acuros XB (AXB) is a novel algorithm implemented to the commercial vender of Varian Eclipse treatment planning system. It is developed to improve the accuracy of dose calculation in external beam radiotherapy, especially in heterogeneity region. Objectives: To evaluate dosimetric impact of AXB algorithm in basic beam characteristics and clinical applications according to IAEA TRS 430 protocol. Materials and methods: Scanning percentage depth doses (PDDs) from CC13 ionization chamber and beam profiles at 10 cm depth from PFD diode of 6 MV from TrueBEAM linear accelerator were obtained in water phantom. Output factors were measured at 10 cm depth using CC13 chamber. Doses of fifteen cases in each 3D-CRT, IMRT, and VMAT techniques in solid phantom and CIRS thorax phantom were measured with CC13 chamber. All measurement results were compared with calculation from Eclipse treatment planning system (TPS) using AXB algorithm. Results: The results showed good agreement between measured and calculated PDDs with δ1 (high dose & small dose gradient) less than 1.5% and δ2 (high dose & large dose gradient) within 1.5 mm. Measured profiles also displayed the coincidence results with TPS, which showed δ2 less than 2 mm, δ3 (high dose & small dose gradient) within 3%, δ4 (low dose & small dose gradient) within 3%, and δ50-90 within 2 mm as the recommendation from IAEA TRS 430 protocol. Maximum output factors differences were only -1.54%. Clinical plans exhibited the dose differences between measurement and calculation in 3D-CRT, IMRT, and VMAT of -0.12±0.38%, -1.59±0.93%, and 0.87±1.24% for homogeneous phantom and 0.27±0.29%, -0.60±1.05%, and -1.12±0.44% for inhomogeneous phantom, respectively. Conclusion: Dose differences between measurement and AXB algorithm calculation are within the recommendation of IAEA TRS 430. AXB algorithm is acceptable for dose calculation in external beam radiotherapy.

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%.

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. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusion: Formulation parameters like viscosity can have an impact on dose delivery using hypodermic syringes for intravitreal injections and on the resulting glide force. [ABSTRACT FROM AUTHOR]

Background: This study aimed to confirm that the incremental dose/clicks system dispenses accurate doses for the Merck family of fertility pen injectors., Research Design and Methods: Set doses (V set ) for three dose dial settings (minimum dose [V min ], midpoint dose [V mid ] and maximum dose [V max ] for the follitropin alfa, choriogonadotropin alfa [D2 classification: single use/variable dose], and follitropin alfa:lutropin-alfa 2:1 combination pen injectors) or a single V set for the choriogonadotropin alfa (D1 classification: single use/single dose) were assessed. Last dose administered by the multi-dose device was assessed for the 900 IU, 450 IU, 300 IU and 150 IU follitropin alfa, and the 900:450 IU, 450:225 IU and 300:150 IU follitropin alfa:lutropin-alfa 2:1 combination pen presentations., Results: Dose accuracy tests for V min , V mid and V max for the follitropin alfa and the follitropin alfa:lutropin-alfa 2:1 combination pen injectors, and last dose administered, were within acceptable limits according to ISO 11,608-1:2012/2014. Dose accuracy tests for the single use/single dose device classification and the single use/variable dose device classification of the choriogonadotropin alfa pen injector were also within the acceptable limits, according to ISO 11608-1:2000/2014., Conclusions: The Merck family of fertility pen injectors functions reliably and the incremental dose/clicks system dispenses accurate doses.

Purpose: The purpose of this research was to develop a system that can read and report the volume of liquid medication present in syringes. Methods: The system is comprised of a digital webcam which is designed to communicate with a computer program developed using MATLAB. The system includes two functional modules, one supporting syringe classification, and another supporting volume measurement. Adaptive template matching was used to determine the best match point between target and template images. The connected component labeling method was used during volume measurement. An artificial neural network (ANN) model was developed using MATLAB to support the intended volume measurement functionality. The developed ANN was designed as a classifier which determines the plunger depth of the syringe and then leverages this result to calculate and derive the volume of medication inside the syringe as the final system output. Commercial Luer-lock syringes of sizes from 1 to 30 ml were used in conjunction with syringe tip caps of blue and yellow color. Tap water or aqueous dye solutions of yellow, red, and blue color simulated liquid medication in the syringe. Results: The developed syringe classification system successfully detected and categorized all tested syringes according to their size. The best accuracy of the system was found to be 99.95% with a 3-ml syringe, while the worst accuracy was 95.82% with a 5-ml syringe. It took approximately 6 s to perform the entire task demonstrating the utility of this system to report volumes in real time. Conclusion: The developed system can be used across a variety of settings that routinely support measuring and handling liquids in syringes including hospitals, pharmacies, and the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Background: Recent studies demonstrate variable results of the accuracy with which patch pumps infuse insulin. Aim of this evaluation was to measure dose accuracies of the patch pump mylife™ OmniPod® (OP) in comparison with the durable insulin pump MiniMed® 640G (MM) simulating real-life clinical situations under laboratory conditions. Methods: Thirty-two OP and 15 MM were tested using insulin aspart at five different boluses (0.5, 1, 5, 10, and 15 international units [IU]) and three basal rates (0.2, 0.6, and 1.8 IU/h) at different time points during a 70 h investigation period. Owing to malfunctions only 22 OP and 11 MM could be analyzed. Dose accuracy was measured by an experimental setting based on IEC 60601-2-24:2012 with determination of weight differences of insulin collection tubes before and after experiments using a precision scale. A maximal tolerance of ±5% for boluses and basal rates was considered adequate according to IEC 60601-2-24:2012. Results: For the five boluses, the percentages of measurement results within the ±5% accuracy threshold were as follows: OP (18.6%, 26.5%, 89.0%, 96.0%, and 96.0%); MM (21.7%, 44.1%, 88.1%, 98.3%, and 100.0%). Both pumps were more accurate at higher bolus volumes (5, 10, and 15 IU), later bolus periods, and if the accuracy threshold was lowered to <10%, <15%, or >15%. For the three basal rates, the percentages within the ±5% accuracy threshold were as follows: OP (66.7%, 22.7%, and 16.7%); MM (14.3%, 0.0%, and 0.0%). Conclusion: This study demonstrates low accuracy for basal rates and single bolus deliveries at low insulin doses for both pump models. Clinicians should be aware of this variability when initiating insulin pump therapy especially in insulin-sensitive patients with low insulin dose requirements. [ABSTRACT FROM AUTHOR]

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.

Flat panel displays (FPD) are electronic viewing technologies used to let people see content in media and entertainment, consumer electronics, personal computer and mobile devices. Other applications and industries are medical, transportation and industrial equipment. FPD is often the preferred choice due to lower weight and less power consumption. Common types of FPD are liquid crystal display (LCD), plasma display panels (PDP) and organic light‐emitting diode (OLED). The global market for FPD continues to grow due to the high demand in the automobile and smartphone industries. As a result of the high demand, the FPD manufacturing industry continues to remain highly competitive. In this cost sensitive arena, FPD manufacturers need to find new ways to reduce the cost of ownership of lithography equipment. Most lithography systems in FPD manufacturing plants use high power mercury ARC lamps to generate i‐line (365nm) wavelength for the photoresist exposure process. This is a costly process as the mercury ARC lamps have a limited lifetime, typically less than one month, which results in downtime to swap lamps.. The cost of replacing the high power mercury ARC lamp, together with the high electricity consumption, and disposal of mercury waste, turns out to be a substantial operating cost. This paper will demonstrate how the use of ultraviolet light emitting diode (UV LED), in replacing the high power mercury lamp, will reduce the overall operating cost which therefore lowers the cost of ownership of the stepper. The breakdown of cost structure will be discussed in detail and show that UV LED is a good replacement solution for the high power mercury ARC lamp. The throughput improvement by using UV LED will also be discussed and compared to the conventional high power mercury arc lamp. The analysis will also show that the consistency of throughput, as compared to the degradation of mercury arc lamp intensity, as well as the time saved for replacement further reduces operating costs. This paper also demonstrates the improved performance of dose accuracy and repeatability, as well as the capability to achieve extremely low exposure doses without compromising dose accuracy. The improvement in stepper reliability by removing the conventional shutter moving parts will also be discussed. The performance data for illumination intensity, dose accuracy, uniformity, spectral line width, CD uniformity and cost reduction will be discussed in detail. The final analysis will show that moving to UV LED illumination offers lower cost and better performance. [ABSTRACT FROM AUTHOR]

Objective Standard ampoules and prefilled syringes of adrenaline are widely available in Australasian EDs for use in cardiac arrest. We hypothesise that prefilled syringes can be administered more rapidly and accurately when compared with the two available standard ampoules. Methods This is a triple arm superiority study comparing the time to i.v. administration and accuracy of dosing of three currently available preparations of adrenaline. Results In their standard packaging, prefilled syringes were on average more than 12 s faster to administer than the 1 mL 1:1000 ampoules and more than 16 s faster than the 10 mL 1:10 000 ampoules ( P < 0.01 in both comparisons). With packaging removed, the time to administration was equal for the 1 mL (1:1000) ampoule and the prefilled syringe. Accuracy of dosing was excellent with both the 10 mL (1:10 000) ampoules and prefilled syringes. The 1 mL (1:1000) ampoules delivered a small number of markedly inaccurate doses, but these did not reach statistical significance. Conclusions The speed of administration of adrenaline utilising a Minijet (CSL Limited, Parkville, Victoria, Australia) is faster than using adrenaline in glass ampoules presented in their plastic packaging. Removing the plastic packaging from the 1 mL (1 mg) ampoule might result in more rapid administration similar to the Minijet. Resuscitation personnel requiring rapid access to adrenaline should consider storing it as either Minijets or ampoules devoid of packaging. These results might be extrapolatable to other clinical scenarios, including pre-hospital and anaesthesia, where other drugs are required for rapid use. [ABSTRACT FROM AUTHOR]

One application in the medical treatment at very small flow rates is the usage of an Insulin pump that delivers doses of insulin at constant cycle times for a specific basal rate as quasi-continuous insulin delivery, which is an important cornerstone in diabetes management. The calibration of these basal rates are performed by either gravimetric or optical methods, which have been developed within the European Metrology Program for Innovation and Research (EMPIR) Joint Research Project (JRP) 18HLT08 Metrology for drug delivery II (MeDDII). These measurement techniques are described in this paper, and an improved approach of the analytical procedure given in the standard IEC 60601-2-24:2012 for determining the discrete doses and the corresponding basal rates is discussed in detail. These improvements allow detailed follow up of dose cycle time and delivered doses as a function of time to identify some artefacts of the measurement method or malfunctioning of the insulin pump. Moreover, the calibration results of different basal rates and bolus deliveries for the gravimetric and the optical methods are also presented. Some analysis issues that should be addressed to prevent misinterpreting of the calibration results are discussed. One of the main issues is the average over a period of time which is an integer multiple of the cycle time to determine the basal rate with the analytical methods described in this paper., (© 2022 the author(s), published by De Gruyter, Berlin/Boston.)

Abstract: Background: Growth hormone (GH) is used to treat pediatric and adult GH deficiency (GHD) and growth failure in, among others, patients with Turner syndrome or children born small for gestational age. To improve treatment adherence, self-injection devices should be easy to learn, easy to use, and well accepted, especially in pediatric patients. Several GH pen devices are available, each with distinct features designed for specific patient needs. Objectives: This study compared injection time and intuitiveness of a prefilled test injection device (Norditropin FlexPro, Novo Nordisk A/S, Bagsværd, Denmark) with those of 2 commercially available durable injection devices (easypod, Merck Serono SA, Geneva, Switzerland; and Genotropin, Pfizer Inc, New York, New York) in GH-treated pediatric patients. Dose accuracy, application errors, intuitiveness, usability, device features, ease of learning, ease of use, and overall preference were also assessed. Methods: This noninterventional, randomized, openlabel, crossover study enrolled patients aged ≥10 to <18 years who were diagnosed with GHD or Turner syndrome or were born small for gestational age. Patients were allocated to an intuitiveness group (without instruction) or an instruction group and assigned to 1 of 3 sequences of device testing. For each device, time taken to deliver a mock injection of test medium (FlexPro) or GH (easypod and Genotropin) into an Eppendorf tube and the delivered dose were measured. Dose accuracy and application errors were assessed by a health care professional. Patients assessed the intuitiveness (intuitiveness group only), device features, ease of learning, ease of use, and overall preference of the devices using questionnaires. Results: Included in the study were 56 patients (mean [SD] age, 13.6 [2.1] years; 63% male; GHD, 44 patients; Turner syndrome, 3; born small for gestational age, 9): 30 in the intuitiveness group and 26 in the instruction group. In the intuitiveness group, the mean (SD) mock injection time was significantly shorter with FlexPro (47.0 [49.0] seconds) than with the easypod (219.2 [72.6] seconds; P < 0.001) or the Genotropin pen (95.1 [78.4] seconds; P < 0.01). In the instruction group, injection time was also shortest with FlexPro (30.7 [10.8] seconds vs 59.6 [13.1] with easypod and 40.7 [18.6] with the Genotropin pen; both, P < 0.001). Most patients (70%) ranked FlexPro as the most intuitive device (easypod, 0%; Genotropin, 30%). In both the intuitiveness and instruction groups, a significantly greater proportion of patients considered FlexPro easiest to learn compared with the easypod and Genotropin devices (both, P < 0.001), although more patients preferred the easypod or Genotropin devices than FlexPro with regard to appearance (intuitiveness group: FlexPro, 8 patients; easypod, 9; and Genotropin, 13; instruction group: FlexPro, 4; easypod, 10; and Genotropin, 12) and quality (intuitiveness group: FlexPro, 6 patients; easypod, 10; and Genotropin, 14; instruction group: FlexPro, 8; easypod, 12; and Genotropin, 6), and easy- pod''s delivery feedback feature was preferred by more patients (intuitiveness group: FlexPro, 8 patients; easypod, 14; Genotropin, 8; instruction group: FlexPro, 8; easypod, 14; and Genotropin, 4). Dose accuracies (as assessed by weighing the delivered dose and calculating variation in the delivered dose by device) were 4.6% with FlexPro, 14.6% with easypod, and 20.6% with the Genotropin pen in the intuitiveness group, and 2.7% with FlexPro, 5.8% with easypod, and 24.4% with the Genotropin pen in the instruction group. Conclusion: In this study, Norditropin FlexPro was associated with shorter injection times, higher dose accuracy, and greater intuitiveness, and was rated as easier to learn compared with the easypod and Genotropin devices. [Copyright &y& Elsevier]

Objective: The dose accuracy of the NovoPen® 4 (Novo Nordisk A/S, Bagsvaerd, Denmark) insulin delivery device was evaluated before and after simulation of 5 years of use and under conditions of mechanical and temperature stress. Methods: To simulate 5 years of use of the NovoPen 4, ≥5475 injections were performed automatically, corresponding to 3 daily injections for 5 years. Accuracy in the delivery of 1-, 30-, and 60-U insulin doses before and after simulation of 5 years of use was assessed over the in-use temperature range (5°C–40°C [41°F–104°F]). The durability and dose accuracy of the NovoPen 4 were also assessed after exposure to extremes of temperature (−40°C and 70°C), high relative humidity (95% RH), and mechanical challenges (freefall from 1.5 m at ambient temperature and from 1 m at 5°C, 40°C, and 95% RH). Results: The dose accuracy of the NovoPen 4 before and after 5 years of simulated use was within International Organization for Standardization 11608-specified limits for all doses studied. Dose accuracy remained within specifications for all doses after exposure to variations in temperature and humidity, and after freefall. Conclusion: The NovoPen 4 exhibited dose accuracy before and after simulation of 5 years of use, across a wide range of temperature and humidity conditions, and after mechanical challenges. [Copyright &y& Elsevier]

FlexPen® is a widely used, prefilled, insulin-delivery pen for patients with Type 1 or Type 2 diabetes. Well-designed trials suggest that FlexPen is more accurate than other prefilled pens at high, medium and low doses. Furthermore, FlexPen is preferred to the vial-and-syringe method by patients, but comparisons of patient preference for modern pens are currently lacking. Next Generation FlexPen® has similar accuracy to FlexPen but has improved patient perception. FlexPen improves adherence and reduces costs compared with the vial-and-syringe method, but the relative adherence and/or cost benefits of different pens are unknown. Important improvements in Next Generation FlexPen include: a significantly reduced injection force (that is lower than the injection force of other prefilled pens) and clearer labeling for insulin-type differentiation. Current evidence suggests that FlexPen and Next Generation FlexPen are an attractive choice when considering insulin-delivery methods. [ABSTRACT FROM AUTHOR]

Background: A thorough Human Factors Engineering (HFE) process was implemented to develop a new Teriparatide Pen for the treatment of osteoporosis. The pen provides a cost-effective treatment alternative to branded teriparatide pens. The HFE process ensured that the pen was safe and effective to use and fulfilled the regulatory requirements., Research Design and Methods: The HFE process utilized a risk-based approach that included understanding the users and other use characteristics, preliminary analyses including a thorough risk assessment, a formative and two validation studies. The studies were carried out with intended users - patients, caregivers and healthcare professionals (HCPs) - in the form of simulated use assessments., Results: The preliminary analyses supported the design of the pen's user interface, including its Instructions for Use (IFU). The formative study helped to optimize the user interface. The validation study results were largely favorable but indicated a minor scope for improvement. The IFU was therefore further improved, and a bridging validation study assessed the revised IFU and found it to be effective in supporting the correct use of the pen., Conclusions: The HFE process ensured and demonstrated that the Teriparatide Pen was safe and effective for its intended use.

Purpose: This study aims to establish criteria for convolution dose calculations and an efficient procedure to include the heterogeneity effects in GammaKnife radiosurgery (GKRS) treatment plans., Methods and Materials: We analyzed 114 GKRS cases of various disease types, tumor locations, sizes, the number of fractions, and prescription doses. There was a total of 205 tumors. CT scans were performed in addition to routine MRI scans for all treatments. All treatment plans were created using the TMR10 algorithm (TMR10). We repeated the dose calculations for this study with the convolution algorithm (Conv). We calculated the ratios between Conv and TMR10 of the treatment volume (TxtVol), the volume covered by half of the prescription dose (TxtVol2), the minimum, maximum, and mean doses in the tumor (minDose, maxDose, and meanDose), and the volume of tumor covered by the prescription isodose (covVol). We then categorized those quantities for locations of tumors represented by the shortest distance of the skull surface from the tumor center (distC) and the tumor edge (distE). [Table: see text]., Results: All six ratios increased with increasing distC and distE. For example, the median minDose ratio increased from 0.885 to 0.933 as distE increased. There was a statistically significant difference in the minDose ratio between tumors of distE < 2 cm and distE ≥ 2 cm. On the other hand, the median maxDose ratio was about 0.933 [0.928-0.939], being almost independent of distE. This suggested a 6.1% overestimation of the delivered dose with TMR10., Conclusion: The heterogeneity effects must be considered for the volume dose calculations by applying the convolution algorithm when the distance of the skull surface from the closest point of the tumor is less than 2 cm to achieve less than 3% accuracy., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose., (© 2023 Old City Publishing, Inc.)

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Cytostatic drugs are increasingly being prepared with a cytostatic robot, though it is not known whether the dose of the final product is more accurate after automated or manual preparation. This study is the first to compare accuracy and precision of automated preparations with manual preparations by measuring volumes and drug concentrations. The accuracy and precision of automated and manual preparations were compared by gravimetric and concentration measurements. During ten days 80 solutions were prepared; 40 robot preparations and 40 manual preparations. With both preparation methods, 20 methotrexate (MTX) and 20 cyclophosphamide (CP) bags were compounded. We simulated normal working conditions by performing the preparations on Monday till Friday. The MTX and CP concentrations were measured with validated ultra high performance liquid chromatography (UHPLC) methods on the last preparation day. With UHPLC analysis, dose accuracy (mean dose error) of robotic or manual preparation of MTX were 1.70% and 0,96% respectively. With gravimetric analysis, these values were 0.50% and 1.96%. Precision (standard error) of the robotic preparation for MTX was significantly smaller than that of manual preparation (p < 0.001). Dose accuracy (mean dose error) of robotic or manual preparation of CP, with UHPLC analysis, were 6.10% and 5.20% respectively. With gravimetric analysis, these values were 0,67% and 0,18%. We conclude that both robotic and manual compounding produce accurate cytostatic products in which the mean percentage of active substance differs by less than 10% from the prescribed amount. Both preparation methods are compliant with the Dutch Medicines Act and the European Pharmacopoeia. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Objective: An accuracy test method is proposed to reduce the amount of reagents used in the test and reduce the cost of spot checks and self-tests., Methods: According to the requirements of dose accuracy test in standard atmospheric conditions in ISO 11608-1:2014, dose accuracy test is carried out for the same batch of reusable pen injector samples by using the test method proposed in this paper and the test method in relevant foreign research, and the data measured by the two methods are processed., Results: After experimental testing and analysis, the data measured by the two methods did not exceed the dose accuracy limit specified in the ISO standard. There was no significant difference between the two methods when the dose of 60 U and 30 U were tested, but there was significant difference when the dose of 1 U was tested., Conclusions: Both methods can be used to evaluate dose accuracy, however, the method proposed in this paper can reduce the usage of drugs by 2/3, so it can reduce cost of supervised test.

In the current issue of Journal of Diabetes Science and Technology, Dreon et al give a comprehensive overview of the technical performance of a wearable patch for bolus insulin delivery. The test results generated by the manufacturer of the bolus-patch provide the technical prerequisites for clinical application. As the device received FDA clearance already in 2010, positive results from the nonclinical performance testing were to be expected, but present nevertheless interesting insights into the device development. The single-dose accuracy verification results seem especially promising, but tighter accuracy criteria could have been specified and information on outliers is missing from the analysis. The clinical application of the bolus-patch is currently under investigation in a large-scale 44-week intervention trial.

Half-unit insulin pens (HUPs) offer finer gradation of insulin dosing than their integer-unit counterparts, tackling the inaccuracies of dose rounding that make it difficult for insulin-sensitive populations to achieve tight glycemic control. This article analyzes the first prefilled HUP, the Humalog Junior KwikPen, in the context of other, similar devices and the developing landscape of smart insulin pens. The Junior KwikPen's suitability for pediatric patients is assessed in reference to a recent study surveying its accuracy and usability under varying conditions intended to simulate real-world use.

Background: This study examines the utility of the first prefilled, rapid-acting insulin pen that can be dialed in half-unit increments. Dose accuracy and injection force were examined through a series of design-verification tests, and usability was established by human factors validation testing., Methods: Devices were tested for dose accuracy at 3 different doses and temperatures and under free fall, vibration, and cold storage conditioning. Injection force was measured at the maximum dose (30 units). Both experiments used the same semiautomated testing system. Usability was validated in a human factors simulated-use study that included 60 participants (patients with type 1 or type 2 diabetes [aged 10-79 years], adult caregivers, and health care providers)., Results: The pen met the International Organization for Standardization (ISO) 11608-1:2014 requirements for dose accuracy at all settings and conditions tested. Furthermore, all individual results were within the ISO specification limits. Mean injection force across temperature settings ranged from 9.25 to 10.85 N at the highest dose. The usability validation study confirmed that use-related risks were reduced to the extent possible and that additional modifications were not likely to afford further reductions., Conclusions: The results from these studies demonstrated accurate dosing over the dose range (0.5-30 units) at different temperatures and conditions with an injection force that should accommodate the intended users. Use safety and usability in patients with diabetes, caregivers, and health care professionals were validated. The added convenience of this new half-unit, prefilled pen may ease the burden of diabetes management for patients who require smaller incremental dosing.

X-ray computed tomography (CT) is widely used in radiation therapy treatment planning in recent years. However, metal implants such as dental fillings and hip prostheses can cause severe bright and dark streaking artifacts in reconstructed CT images. These artifacts decrease image contrast and degrade HU accuracy, leading to inaccuracies in target delineation and dose calculation. In this work, a metal artifact reduction method is proposed based on the intrinsic anatomical similarity between neighboring CT slices. Neighboring CT slices from the same patient exhibit similar anatomical features. Exploiting this anatomical similarity, a gamma map is calculated as a weighted summation of relative HU error and distance error for each pixel in an artifact-corrupted CT image relative to a neighboring, artifact-free image. The minimum value in the gamma map for each pixel is used to identify an appropriate pixel from the artifact-free CT slice to replace the corresponding artifact-corrupted pixel. With the proposed method, the mean CT HU error was reduced from 360 HU and 460 HU to 24 HU and 34 HU on head and pelvis CT images, respectively. Dose calculation accuracy also improved, as the dose difference was reduced from greater than 20% to less than 4%. Using 3%/3mm criteria, the gamma analysis failure rate was reduced from 23.25% to 0.02%. An image-based metal artifact reduction method is proposed that replaces corrupted image pixels with pixels from neighboring CT slices free of metal artifacts. This method is shown to be capable of suppressing streaking artifacts, thereby improving HU and dose calculation accuracy.

Objectives: The prefilled, multi-dose follitropin alfa (GONAL-f®) pen injector was redesigned based upon user feedback, to improve pen functionality. The dose information display was altered with the intention of improving readability and the dosing mechanism hardware was modified to increase robustness. The dose accuracy of the redesigned pen injector was evaluated under different conditions and after handling processes., Methods: Three studies investigated the dose accuracy of the three presentations (300, 450 and 900 IU) of the redesigned pen injector according to the ISO 11608-1:2012/2014 standard. The dose accuracy was evaluated in cold, standard and warm atmospheres, and subsequent to freefall, vibration, dry-heat, cold-storage and shipping preconditioning. The total extractable volume and dispense force of the pen injector were also investigated., Results: All doses dispensed with all three presentations, under all the conditions examined, were within the limits for accuracy defined by the ISO standard, as was the total extractable volume. The mean ± standard deviation dispense force was 12.5 ± 0.99 and 13.8 ± 1.16 N for the 300 and 900 IU pen injectors, respectively. These are below the upper threshold of the range considered optimal for pen injectors., Conclusions: These studies demonstrate that the redesigned pen injector functions reliably, dispensing accurate doses under the range of conditions studied.

Background: The functional performance of the JuniorSTAR(®) (Sanofi, Paris, France) half-unit insulin pen was evaluated through a series of specific objective tests to assess the dose accuracy, pen weight, injection force, and dialing torque., Method: Pens (n = 60) were tested under standard atmospheric conditions with 3 different types of insulins manufactured by Sanofi (insulin glargine, insulin glulisine, and biphasic insulin isophane). The dose accuracy was tested according to the ISO 11608-1:2012 standards. Injection doses of 0.010, 0.155, and 0.300 ml were evaluated. For mean weight evaluation, the pens without the cartridge were weighed on precision balances. The injection force was measured using a texture analyzer and the dialing torque was measured using a torque meter., Results: JuniorSTAR met the ISO 11608-1:2012 criteria for dose accuracy as all the delivered doses were within the predefined limits for all types of insulin tested. The mean weight of the JuniorSTAR pen was 33.4 g (SD = 0.075). The mean injection force was 6.0 N (SD = 0.8), 4.3 N (SD = 0.4), and 5.1 N (SD = 0.6) for insulin glargine, insulin glulisine, and biphasic insulin isophane, respectively. The mean dialing torque was 5.09 Ncm (SD = 0.29) and 5.88 Ncm (SD = 0.53) for setting and correcting a dose, respectively., Conclusions: Together with results from a previously reported usability survey, these results show that the JuniorSTAR reusable, half-unit pen is a lightweight and accurate device for insulin delivery with a dialing torque and injection force suitable for young people with type 1 diabetes., (© 2015 Diabetes Technology Society.)

Insulin pen delivery systems are preferred by patients over the traditional vial and syringe method for insulin delivery because they are simple and easy to use, improve confidence in dosing insulin, and have less interference with activities and improved discretion with use. Insulin manufacturers have made numerous improvements to their first marketed pen devices and are now introducing their next generation of devices. Design modifications to the newest generation of prefilled insulin pen devices are intended to improve the ease of use and safety and continue to positively impact adherence to insulin. This review focuses on the Next Generation FlexPen(®) with regard to design considerations to reduce injection force, improve accuracy and ease of use, and evaluate the preference of patient and health-care provider compared with other disposable, prefilled insulin pen devices.