The dosing regimen for 17-hydroxyprogesterone caproate was suboptimal: lessons for future pharmacotherapy for pregnant women.

BACKGROUND: Makena (17-hydroxyprogesterone caproate) was approved by the United States Food and Drug Administration for the prevention of recurrent spontaneous preterm birth in 2011 under the accelerated approval pathway, but fundamental pharmacokinetic or pharmacodynamic (Phase 1 and Phase 2) studies were not performed. At the time, there were no dose-response or concentration-response data. The therapeutic concentration was not known. The lack of such data brings into question the dosing regimen for 17-hydroxyprogesterone caproate and if it was optimized. OBJECTIVE: The purpose of this study was to evaluate the dosing regimen for 17-hydroxyprogesterone by analyzing 3 data sets in which the 17-hydroxyprogesterone caproate pharmacology was evaluated, namely the Maternal-Fetal Medicine Omega 3 study, the Obstetric-Fetal Pharmacology Research Units study, and the Obstetrical-Fetal Pharmacology Research Centers study. If an inappropriate dosing regimen could be identified, such information could inform future studies of pharmacotherapy in pregnancy. STUDY DESIGN: Data from the Omega 3 study were used to determine if plasma concentration was related to spontaneous preterm birth risk and if a threshold concentration could be identified. Data from the Obstetric-Fetal Pharmacology Research Units study were used to determine the half-life of 17-hydroxyprogesterone caproate and to develop a model to simulate drug concentrations with various dosing regimens. Data from the Obstetrical-Fetal Pharmacology Research Centers study were used to determine the relationship between dose and safety outcomes. RESULTS: Analysis of the Omega 3 data set indicated that the risk for spontaneous preterm birth decreased as the log concentration of 17-hydroxyprogesterone caproate increased (odds ratio, 0.04; 95% confidence interval, 0.00-0.90). A steady state concentration of >9 ng/mL (equivalent to >8 ng/mL at 25-28 weeks) was associated with the lowest risk for spontaneous preterm birth (hazard ratio, 0.52; 95% confidence interval, 0.27-0.98; P=.04); this concentration was not achieved in 25% of subjects who received the 250 mg weekly dose. In the Obstetrical-Fetal Pharmacology Research Units study, the adjusted half-life (median and interquartile range) of 17-hydroxyprogesterone caproate was 14.0 (11.5-17.2) days. Simulations indicated that with the 250 mg weekly dose, >5 weekly injections were required to reach the 9 ng/mL target; however, those with the shortest half-life (corresponding to higher clearance), never reached the targeted 9 ng/mL concentration. In 75% of subjects, a loading dose of 500 mg weekly for 2 weeks followed by 250 mg weekly achieved and maintained the 9 ng/mL concentration within 2 weeks but in those 25% with the shortest half-life, concentrations exceeded the 9 ng/mL target for only 3 weeks. In the Obstetrical-Fetal Pharmacology Research Centers study, all 65 subjects who received a weekly dose of 500 mg exceeded the 9 ng/mL steady state. CONCLUSION: The dosing regimen for 17-hydroxyprogesterone caproate was inadequate. There is a significant inverse relationship between drug concentration and spontaneous preterm birth. The risk was lowest when the concentration exceeded 9 ng/mL, but 25% of women who received the 250 mg weekly dose never reached or maintained this concentration. The drug's long half-life necessitates a loading dose to achieve therapeutic concentrations rapidly. The omission of basic pharmacologic studies to determine the proper dosing may have compromised the effectiveness of 17-hydroxyprogesterone caproate. Future pharmacotherapy trials in pregnancy must first complete fundamental pharmacology studies.

Devices for securing and administering pediatric compounded oral liquids: survey results from French university hospitals.

Oral liquid forms, either commercial or compounded, are preferred in pediatrics due to their suitability for weight-based dosing and acceptability for children. The choice of dosing delivery devices associated with oral liquid forms is important to ensure accurate dosing, ease of administration, and patient safety. Given the prevalence of compounding in pediatric settings, this study aimed to investigate the practices among French university hospitals concerning the selection of dosing delivery devices associated with compounding oral liquid forms for children. An online survey was distributed to pharmacists involved in compounding in French university hospitals. The survey covered aspects such as the presence of child-resistant caps, types of dosing devices, the presence of bottle adapters, and the type of bottle adapters used. Among the 36 hospital pharmacies contacted, 24 responded to the survey. One pharmacy employed child-resistant caps for compounded liquid forms. Enteral syringes emerged as the primary dosing device (71%), with a minority using luer/luer-lock syringes (21%). Spoon and measuring cup usage was reported by none. Approximately two-thirds of the pharmacies (67%) used a bottle adapter in conjunction with the sampling device.   Conclusion: The study highlighted diversity in the practices of French university hospitals regarding dosing delivery devices associated with compounding oral liquid forms for pediatric patients. The findings underscored the need for standardized guidelines to streamline practices and enhance safety and precision in compounded medication administration for children. What is Known: • Administration devices are important to ensure the correct administration of the required dose of oral liquids in pediatrics. • For compounded oral liquid forms, the selection and supply of administration devices are managed by compounding pharmacies from those available on the market. What is New: • The study highlighted the variability of administration devices associated with compounded liquids for oral use in French hospital pharmacies.

An ethical assessment of compounded bioidentical hormone therapy.

The use of compounded bioidentical hormone therapy (cBHT) continues to grow in popularity despite the availability of many US Food and Drug Administration-approved hormone products produced in different formulations and dosages. Numerous claims made by proponents of cBHT are not substantiated by properly designed studies. Valid concerns about purity, efficacy, bioavailability and safety of cBHT have been raised. Since patient welfare is the first duty of health professionals, promoting and prescribing cBHT as first-line therapy violates a number of ethical tenets of medical and pharmacy practice and should be discouraged without a compelling reason.

The double jeopardy of low family income and negative emotionality: The family stress model revisited.

The family stress model has, for decades, guided empirical work linking poverty with increased risk of child social-emotional dysfunction. The present study extends this line of work by examining whether child negative emotionality moderates associations between family income, family stress (maternal distress, parental locus of control, and relationship dissatisfaction), and later externalizing and internalizing behavior problems. In a longitudinal population-based sample (n ~ 80,000) of Norwegian children followed from birth through age five (The Norwegian Mother, Father, and Child Cohort Study; MoBa), we examined whether high (vs. moderate or low) negative emotionality families would display: (a) compounding stress (i.e., particularly strong associations between low family income and family stress), (b) diathesis-stress (i.e., particularly strong associations between family stress and behavior problems), or (c) double jeopardy (i.e., both compounding stress and diathesis-stress moderating effects). Negative emotionality significantly moderated the association between family income and behavior problems in a manner most consistent with double jeopardy. As a result, compared with children with moderate/low negative emotionality, the family income-behavior problems association was two to three times larger for those with higher negative emotionality. These findings underscore the active role children may play in family processes that link low family income with behavior problems.

Evaluation of a compounding phospholipid base for the percutaneous absorption of high molecular weight drugs using the Franz finite dose model.

BACKGROUND: Permeation-enhancing compounding bases are aimed to facilitate the penetration of the active pharmaceutical ingredients (APIs) across the skin barrier. OBJECTIVES: The purpose of this study was to evaluate the percutaneous absorption of radiolabeled human insulin (14 C-isototpe) when incorporated in a proprietary phospholipid base designed to deliver APIs with high molecular weights (HMW). The aim was not to claim the transdermal delivery of insulin with potential therapeutic applications in diabetes but, instead, to evaluate the ability of the compounding phospholipid base to deliver HMW drugs. METHODS: The percutaneous absorption of 14 C-insulin was determined using human torso skin and the Franz skin finite dose model. Two topical test formulations were prepared for in vitro evaluation: insulin 1% in phospholipid base (standard) and insulin 1% in phospholipid base HMW. The rate of percutaneous absorption (mean flux) and the distribution of 14 C-insulin through the skin were evaluated for both topical test formulations. A two-way ANOVA was used to determine statistical differences. RESULTS: The 14 C-insulin was distributed into the stratum corneum, epidermis and dermis. Mean flux values showed a rapid penetration upon application and the maximum flux was achieved at 30 min, followed by a slow decline. Subsequently, a slower decline was observed for the topical test formulation including the phospholipid base HMW. CONCLUSION: The phospholipid base HMW facilitates the percutaneous absorption of HMW drugs across human cadaver skin and, therefore, it may potentially be a useful option for compounding pharmacists and practitioners when considering the skin for the percutaneous delivery of large drugs.

GLP-1 agonists: A review for emergency clinicians.

INTRODUCTION: Glucagon-like peptide 1 (GLP-1) based therapies, including GLP-1 agonists, are currently in use for treatment of diabetes and obesity. However, several complications may occur with their use. OBJECTIVE: This narrative review provides a focused evaluation of GLP-1 agonist therapy and associated complications for emergency clinicians. DISCUSSION: GLP-1 agonists potentiate insulin release and reduce gastric emptying and food intake. These agents have demonstrated significant improvements in glucose control in diabetics and weight loss in obese patients. The two most common agents include subcutaneous semaglutide (Ozempic, approved for type 2 diabetes, and Wegovy, approved for weight loss) and liraglutide (Saxenda, approved for weight loss, and Victoza, approved for type 2 diabetes), though an oral formulation of semaglutide is available (Rybelsus). While these drugs are associated with improved long-term outcomes, there are a variety of associated adverse events. The most common include gastrointestinal (GI) adverse events such as nausea, vomiting, diarrhea, and abdominal pain. Pancreatitis and biliary disease may also occur. Hypersensitivity including injection site reactions have been associated with use, with reports of anaphylaxis and other rashes. Renal adverse events are most commonly associated with severe GI losses. Hypoglycemia may occur when these agents are used with sulfonylureas or insulin. There is also an increased risk of diabetic retinopathy. Due to the current shortage and expense of these medications, many patients have attempted to obtain these medications from non-licensed and unregulated agents, which may be associated with increased risk of serious complications. CONCLUSIONS: An understanding of the indications for GLP-1 agonist use and associated adverse events can assist emergency clinicians.

An assessment of exposed syringe inner walls as a route of exposure from hazardous drugs.

INTRODUCTION: Maintaining safe working environments for health care personnel, especially for those who regularly handle hazardous drugs (HDs), is of utmost importance. Studies have shown that when closed system transfer devices (CSTDs) are used with standard open barrel syringes, cyclophosphamide (CP), a commonly used HD, is transferred to the syringe plunger during compounding or administration processes. This contamination can then be transferred to the work environment, endangering workers. PURPOSE: The purpose of this study was to quantify HD contamination of the inner surface of standard open barrel syringes and to compare contamination levels between three commonly used HDs: 5-fluorouracil (5-FU), CP, and ifosfamide (IF). METHODS: Each HD was transferred from a vial to an intravenous (IV) bag using a standard open barrel syringe and Becton, Dickinson and Company (BD) PhaSealTM CSTD connectors. Samples were taken from the inner surface of each of the syringe barrels to measure the amount of HD contamination. Each drug was tested 15 times and compared to a positive control. RESULTS: Significant amounts of each drug were transferred to the inner surfaces of the syringes. The average amounts of each drug measured were: 5-FU, 1327.7 ng (standard deviation [SD] = 873.6 ng); CP, 1074.8 ng (SD = 481.6 ng); and IF, 1700.0 ng (SD = 1098.1 ng). There was no statistically significant difference between the three drugs (p = 0.14). CONCLUSION: This study underscores the presence of HD contamination on standard open barrel syringe inner surfaces after transfer of drug from vial to syringe to IV bag. Such contamination could be spread in the working environment and expose health care workers to harm.

Optimum Parameters in Ultrasound Coherent Plane Wave Compounding for High LPWV Estimation: Validation on Phantom and Feasibility in 10 Subjects.

OBJECTIVES: The aim of this study is to determine the optimum and fine values of the number and transmission angles of tilted plane waves for coherent plane-wave compounding (CPWC)-based high local pulse wave velocity (LPWV) estimation. METHODS: A Verasonics system incorporating a linear array probe L14-5/38 with 128 elements and a pulsatile pump, CompuFlow1000, were used to acquire radio frequency data of 3, 5, 7, and 9 tilted plane wave sequences with angle intervals from 0° to 12° with a coarse interval increment step of 1°, and the angle intervals from 0° to 2° with a fine interval increment step of 0.25° from a carotid vessel phantom with the LPWV of 13.42 ± 0.90 m/s. The mean value, standard deviation, and coefficients of variation (CV) of the estimated LPWVs were calculated to quantitatively assess the performance of different configurations for CPWC-based LPWV estimation. Ten healthy human subjects of two age groups were recruited to assess the in vivo feasibility of the optimum parameter values. RESULTS: The CPWC technique with three plane waves (PRF of 12 kHz corresponding to a frame rate of 4000 Hz) with an interval of 0.75° had LPWVs of 13.52 ± 0.08 m/s with the lowest CV of 1.84% on the phantom, and 5.49 ± 1.46 m/s with the lowest CV of 12.35% on 10 subjects. CONCLUSIONS: The optimum parameters determined in this study show the best repeatability of the LPWV measurements with a vessel phantom and 10 healthy subjects, which support further studies on larger datasets for potential applications.

The effects of formulation on the pharmacokinetics of itraconazole and amiodarone in dogs after oral administration of a combination product, commercial products, and compounded products.

This study evaluated four different formulations of itraconazole and amiodarone. Formulation 1 was Vida's combination tablet containing both active pharmaceutical ingredients (APIs). Formulation 2 was separate, commercially available human generic capsules and tablets of itraconazole and amiodarone, respectively. Formulation 3 was separate, compounded suspensions of itraconazole and amiodarone. Formulation 4 was a compounded chewable tablet of itraconazole. Eight female dogs were dosed with 5 mg/kg of itraconazole and 15 mg/kg amiodarone (except for formulation 4, which only received 5 mg/kg itraconazole) once weekly for 4 weeks using a modified Latin Square design, ensuring that all dogs received all formulations with a 7-day washout between treatments. Animals were fasted overnight prior to each dose administration, with food returned to all animals 4 h post-dose. Blood samples (3 mL) were collected pre-treatment (0) and at appropriate time points over 72 h after each dose for a total of 14 samples per dog per treatment. There was high variability in the serum concentration data within treatment groups for itraconazole. The compounded suspensions were difficult to dose due to the nature of the formulations. The volumes dosed were accurate and consistent, but the suspension was thin and settled immediately when shaking was stopped for both itraconazole and amiodarone. All serum samples following itraconazole chewable tablet administration were not detectable or just above itraconazole's LOQ and thus did not allow for pharmacokinetic determination.

A mini review on manipulation of carbohydrate for better use in surimi and surimi products: modification and compounding.

Carbohydrate is widely used in the production of surimi and surimi products to improve their qualities, such as anti-freezing capability, gelling ability, nutrition, flavor and 3D printability. More and more native carbohydrates have been modified through physical methods (e.g., ball milling, irradiation and differential sedimentation), chemical method (e.g., deacetylation, hydroxypropylation and acetic acid esterification) or enzymatic method (e.g., chitosanase) before being used in the processing of surimi and surimi products in recent years. At the same time, different carbohydrates are compounded and applied to surimi and surimi products. The modified and compounded carbohydrates in surimi have been proved to improve quality of surimi and surimi products more pronouncedly than native carbohydrates. Therefore, this review summarizes the manipulation of carbohydrate by modification and compounding to improve the qualities of surimi and surimi products. Moreover, the prospects for carbohydrate modification and compounding for use in surimi and surimi products are discussed. © 2023 Society of Chemical Industry.

Assessment of traditional healers' knowledge and utilization of pharmaceutical equipment and medical supplies in the Amhara region, North West Ethiopia.

CONTEXT: Although pharmaceutical equipment and medical supplies play a vital role in the quality of traditional medicines, they have not received much attention from stakeholders and researchers nationally and internationally. OBJECTIVE: This study assesses traditional healers' knowledge and utilization of pharmaceutical equipment and medical supplies in the Amhara region, North West Ethiopia. MATERIALS AND METHODS: A quantitative cross-sectional study was conducted on 70 traditional healers. The data were collected using an interview-based questionnaire. The collected data were checked and entered into Statistical Package for Social Sciences version 25.0 for analysis. The results were presented as percentages. The association between socio-demographic characteristics and traditional healers' knowledge of pharmaceutical equipment and medical supplies was examined using Pearson's Chi-squares test. RESULTS: About 90% of traditional healers had information about pharmaceutical equipment and medical supplies, and currently 80% of them used different pharmaceutical equipment and medical supplies individually and in combination with traditional equipment. Although most traditional healers used different pharmaceutical equipment and medical supplies, only 13.3% of them used equipment and supplies a day. Only 15% of traditional healers continuously cleaned their equipment. None of the socio-demographic variables were significantly associated to the knowledge of pharmaceutical equipment and medical supplies. DISCUSSION AND CONCLUSIONS: Pharmaceutical equipment and medical supplies used by traditional healers was inconsistent, mainly associated with their habit of using self-prepared and home-available equipment. Moreover, the checkup status of compounding equipment was poor. As Traditional healers provide high-patient care services, emphasis should be given to improving their preparation and treatment strategies.

[Overwiew of compounding oncology pharmacy in France in 2021]. / États des lieux de la pharmacotechnie oncologique en France en 2021.

The pharmacotechnical expert group of the French Society of Oncological Pharmacy presents the results of its national survey carried out in 2021 in the form of an inventory of pharmaceutical compounding units dedicated to oncology. Premises, equipment, controls, production flows and trends are described in this article, providing an overview of the sector at a time when the new Good Manufacturing Practices (GMP) are applicable. This overview will allow us to better address the needs and expectations of production pharmacists regarding the application of GMP and the development of their units.

[Comparative study of production and control processes of parenteral nutritional admixtures in neonatology]. / Étude comparative des processus de production et de contrôle analytique des préparations magistrales de mélanges nutritifs parentéraux en néonatalogie.

OBJECTIVES: To assess the impact of disparities in production and analytical control processes on the quality of parenteral nutrition (PN) preparations produced in the Auvergne-Rhône-Alpes region. METHODS: This study was carried out in four hospital pharmacies of the Auvergne-Rhône-Alpes region. To assess the impact of production processes, each centre produced ten PN preparations from the same prescription. Analytical controls (sodium, potassium and calcium dosage) were carried out on all the preparations. To assess the impact of the control processes, a batch of ten preparations was produced from the same prescription. Samples were sent to the four hospital pharmacies for analytical control (sodium, potassium and calcium dosage). RESULTS: Measurements of relative production bias show that there is a significant difference between the preparations from the four centres in terms of sodium and potassium content. Each centre had at least one production bias for one of the three electrolytes measured. Concerning analytical controls, there was a significant difference between the four centres in the sodium and potassium levels measured. With the exception of calcium, all the centres reported measurements within the usual specifications of±10% of the target value. The results obtained have no clinically significant impact. CONCLUSION: The diversity of NP practices has a real impact on the quality of the preparations made. A regional collaboration should be envisaged to standardise patient care.

Developing a Comprehensive Framework of Safeguarding Strategies to Address Anticipated Errors With Organizational High-Alert Medications.

Purpose: To describe the development of a comprehensive framework of safeguarding strategies to address observed/anticipated errors with organizational high-alert medications. Methods: Observed/anticipated errors were identified for organizational high-alert medications and medication classes based on a review of external literature and alerts as well as internal voluntary error reporting. Anticipated or frequently reported errors were categorized into common cause error types. Error reduction strategies to address each common cause error were identified in collaboration with medication safety specialists and specialty practice pharmacists. Results: The review of externally and internally reported errors identified 101 observed/anticipated common cause errors across the 19 high-alert medication classes (median 5 error types per medication class, interquartile range 3-6). Safeguarding strategies specific to high-alert medications were identified in the following domains: separate or sequestered storage; restricted ordering; active alerts; dispensing in patient-specific dosing, unit of use, or unit-dose packaging; dispensing from pharmacy only; auxiliary labeling; level of care restriction; required monitoring; independent double checks; certification/privileging of staff; specific guidelines for use/monitoring; and other/miscellaneous. Identification of the observed/anticipated errors and the associated safeguarding strategies facilitated the development of a comprehensive tool and visual framework for addressing common cause errors associated with organizational high-alert medications. Conclusion: A comprehensive framework of safeguarding strategies to address anticipated errors with organizational high-alert medications is proposed. Although individual safeguards are institution-specific, the framework can be leveraged by all hospitals in order to take inventory of error-reduction strategies and prospectively identify gaps to address common cause errors.

A Virtual Reality 360 Video to Introduce Second-Year Student Pharmacists to Sterile Compounding Prior to Course Activity.

Background: Virtual reality (VR) has not been used in pharmacy education when teaching sterile compounding. Objective: The objective of this study was to describe the development of a VR 360 video for second-year student pharmacists. The secondary objective was to assess the VR experience, specifically on participants' knowledge and performance in sterile compounding, as well as the VR video demands and efforts. Methods: This cross-sectional, open-label randomized study developed a VR 360 video introducing sterile compounding, created with Insta360 Pro and GoPro cameras. The video creation required two individuals to record and one individual to edit for approximately 12 hours of creation time. Participants' knowledge and performance were assessed through ten knowledge questions and the class activity rubric. The NASA Task Load Index (TLX) measured the VR experience demands and efforts for the VR sterile compounding introduction. Results: Of the 98 second-year student pharmacists, 19 consented to the study with 7 in the VR group and 12 controls. Student knowledge increased from 6.33 (0.8) to 8 (1.2) for the VR group and 7 (0.7) to 8 (0.7) for the control group. Performance for the classroom activity was 23.71 (0.3) for the VR group and 22.96 (0.9) for the control group. The NASA TLX values demonstrated positive findings for the VR experience. Conclusion: With the limited study enrollment, comparative analysis between standard materials and the VR 360 video could not be determined. This article describes the creation of a VR sterile compounding 360 video with excerpts included. Future studies to compare traditional materials to VR will be completed in the future.

The extreme 2016 wheat yield failure in France.

France suffered, in 2016, the most extreme wheat yield decline in recent history, with some districts losing 55% yield. To attribute causes, we combined the largest coherent detailed wheat field experimental dataset with statistical and crop model techniques, climate information, and yield physiology. The 2016 yield was composed of up to 40% fewer grains that were up to 30% lighter than expected across eight research stations in France. The flowering stage was affected by prolonged cloud cover and heavy rainfall when 31% of the loss in grain yield was incurred from reduced solar radiation and 19% from floret damage. Grain filling was also affected as 26% of grain yield loss was caused by soil anoxia, 11% by fungal foliar diseases, and 10% by ear blight. Compounding climate effects caused the extreme yield decline. The likelihood of these compound factors recurring under future climate change is estimated to change with a higher frequency of extremely low wheat yields.

Spatio-temporal compounding of connected extreme events: Projection and hotspot identification.

In general, the impact of two different connected extreme events is noticed on the same duration and spatial area. However, the connected extreme events can have footprint over different temporal and spatial scales. Thus, this article analyses the connected extreme events over India using the spatio-temporal compounding technique to understand the impact at different temporal and spatial scales. This approach is applied to analyse the historical and future connected extreme events. In the present study, coincident heat waves and droughts (Event C1), coincident heat waves and extreme precipitation (Event C2) are considered as connected extreme events. The future events are investigated using the suitable global climate models (GCMs) projections under three climate change scenarios (Shared Socioeconomic Pathways (SSP) 2-4.5, SSP3-7.0, and SSP5-8.5). The suitable GCMs are identified with the help of compromise programming. Subsequently, the hotspot regions are identified applying the Regional Climate Change Index (RCCI) method. The outcomes from the study suggest that with increasing temporal compounding, the mean duration of extreme events also increases. Highest increase in mean duration is observed for Event C1 over PI (Peninsular India), WCI (West Central India), and some parts of CNI (Central Northeast India) regions. The regions with high magnitude of duration have low magnitude of occurrence. The duration of Event C1 is likely to increase with respect to climate change scenarios and temporal compounding, especially in the PI region and some parts of WCI. However, there is insignificant change in the duration of Event C2. The PI region identified as the most vulnerable region followed by WCI and HR regions. The highest percentage of area under the emerging hotspot category is noticed under SSP5-8.5 climate change scenario.

Inferential properties with a novel two parameter Poisson generalized Lindley distribution with regression and application to INAR(1) process.

Based on the well-known Poisson (P) distribution and the new generalized Lindley distribution (NGLD) developed by using gamma (α,θ) and gamma (α-1,θ) distributions, a new compound two-parameter Poisson generalized Lindley (TPPGL) distribution is proposed in this paper and thereon systematically explores the mathematical properties. Closed form expressions are assembled for such properties including the probability generating function, moments, skewness, kurtosis, etc. The likelihood-based method is used for estimating the parameters followed by a broad Monte Carlo simulation study. To further motivate the proposed model, a count regression model and a first order integer valued autoregressive process are constructed based on the novel TPPGL distribution. The empirical importance of the proposed models is confirmed through application to four real datasets.

Conceptual combination during novel and existing compound word reading in context: A self-paced reading study.

According to the relation-interpretation-competition-evaluation (RICE) hypothesis, compound word processing involves selecting a relational meaning (e.g., moonlight is 'light from moon') from a larger set of competing possible relational meanings. Prior lexical decision experiments with existing compound words have demonstrated that greater entropy of conceptual relations, i.e., greater competition between conceptual relations, impedes lexical processing speed. The present study addresses two unresolved issues: First, it is unclear whether the competition effect generalizes to the processing of novel compounds (e.g., grassladder), and second, it is not yet known whether competition between possible relational meanings extends to compounds when they are read in a sentence context. A series of self-paced reading tasks examined whether the competition effect operates regardless of (i) compound type (existing vs. novel), and (ii) whether sentence context (semantically supportive vs. semantically non-supportive) moderates the competition effect. The experiments confirmed that reading times of novel and existing compounds read in sentences were impacted by entropy of conceptual relations. Moreover, the effect was equally strong in both sentence context types. Additional analyses indicated that relational meanings are more ambiguous and flexible across different contexts for novel compounds compared to existing compounds.

Extemporaneous compounding of dabrafenib and trametinib for cancer patients with feeding tubes.

INTRODUCTION: Dabrafenib and trametinib are oral targeted agents indicated for BRAF mutated non-small cell lung cancer and melanoma. There is little data to support the administration of these two agents via enteral feeding tube. This case series describes three patients who received compounded dabrafenib and trametinib suspensions through enteral feeding tubes. CASE REPORT: We present three patients who required dabrafenib and trametinib to be prepared as a non-standard compound for the medications to be administered via feeding tube. The patients were diagnosed with with BRAF mutated cancers including melanoma, non-small-cell lung carcinoma, and anaplastic thyroid cancer. In all three cases, there was evidence of initial disease response on imaging, and there were no unexpected toxicities secondary to dabrafenib and trametinib. DISCUSSION: There are patients that are unable to tolerate medications by mouth due to dysphagia, anatomical malfunctions, or other digestive disorders. There is limited literature that describes preparation of trametinib and dabrafenib into an enteral suspension. Identifying a safe and efficacious method of administering these two medications via feeding tube ensures that these patients continue to be able to receive them as part of their anti-cancer therapy. CONCLUSION: Despite the lack of available data, compounding of dabrafenib and trametinib may be clinically appropriate when benefits outweigh the risk of unconventional administration. Further studies are warranted to assess for the pharmacokinetics, pharmacodynamics, stability, and storage for these liquid medications.