A modelling approach to prepare synthetic urine for struvite precipitation studies.

Nutrient recovery from wastewater is an effective strategy to prevent eutrophication and provide value for the treatment process. Human urine is a small but highly nutrient-rich stream in the total flux of domestic wastewater from which struvite (MgNH4PO4.6H2O) could be recovered and used as a fertiliser. Consequently, synthetic urine was used in most struvite precipitation studies, due to biohazard issues in real human urine. A modelling approach was developed to formulate synthetic urine recipes based on elemental urine composition, using matrix solving strategy to select and quantify chemical salts for synthetic urine preparation. The model also included mass balance, chemical speciation, and equilibrium dissociation expression for solution thermodynamics predictions in the formulated urine. In this study, synthetic solutions of fresh and stored urine were assessed with this model using Engineering Equation Solver (EES) software to calculate the quantity of salts, pH, ionic strength, and struvite saturation index. Simulation results in EES were successfully verified using PHREEQC simulations, while model validation comprised the examination of urine composition with their reported recipes.

Filled Carbon Nanotubes as Anode Materials for Lithium-Ion Batteries.

Downsizing well-established materials to the nanoscale is a key route to novel functionalities, in particular if different functionalities are merged in hybrid nanomaterials. Hybrid carbon-based hierarchical nanostructures are particularly promising for electrochemical energy storage since they combine benefits of nanosize effects, enhanced electrical conductivity and integrity of bulk materials. We show that endohedral multiwalled carbon nanotubes (CNT) encapsulating high-capacity (here: conversion and alloying) electrode materials have a high potential for use in anode materials for lithium-ion batteries (LIB). There are two essential characteristics of filled CNT relevant for application in electrochemical energy storage: (1) rigid hollow cavities of the CNT provide upper limits for nanoparticles in their inner cavities which are both separated from the fillings of other CNT and protected against degradation. In particular, the CNT shells resist strong volume changes of encapsulates in response to electrochemical cycling, which in conventional conversion and alloying materials hinders application in energy storage devices. (2) Carbon mantles ensure electrical contact to the active material as they are unaffected by potential cracks of the encapsulate and form a stable conductive network in the electrode compound. Our studies confirm that encapsulates are electrochemically active and can achieve full theoretical reversible capacity. The results imply that encapsulating nanostructures inside CNT can provide a route to new high-performance nanocomposite anode materials for LIB.

Biosimilars: Considerations for Payers.

Evaluating biosimilars requires payers to go beyond cost considerations: safety and efficacy, reliability of supply and logistics, and the impact of state laws on substitution and interchangeability must all be deliberated.

Silver removal from aqueous solution by biochar produced from biosolids via microwave pyrolysis.

The contamination of water with silver has increased due to the widespread applications of products with silver employed as antimicrobial agent. Adsorption is a cost-effective method for silver removal from aqueous solution. In this study biochar, produced from the microwave assisted pyrolysis of biosolids, was used for silver removal from an aqueous solution. The adsorption kinetics, isotherms and thermodynamics were investigated to better understand the silver removal process by biochar. X-ray diffraction results demonstrated that silver removal was a combination two consecutive mechanisms, reduction and physical adsorption. The Langmuir model fitted the experimental data well, showing that silver removal was predominantly a surface mechanism. The thermodynamic investigation demonstrated that silver removal by biochar was an exothermic process. The final nanocomposite Ag-biochar (biochar plus silver) was used for methylene blue adsorption and photodegradation. This study showed the potential of using biochar produced from biosolids for silver removal as a promising solution to mitigate water pollution and an environmentally sustainable approach for biosolids management and re-use.

Biochar produced from biosolids using a single-mode microwave: Characterisation and its potential for phosphorus removal.

The amount of biosolids increases every year, and social and environmental concerns are also rising due to heavy metals and pathogen contamination. Even though biosolids are considered as a waste material, they could be used as a precursor in several applications, especially in agriculture due to the presence of essential nutrients. Microwave assisted pyrolysis (MWAP) is a promising technology to safely manage biosolids, while producing value-added products, such as biochar, that can be used to improve soil fertility. This study examined the impact of pyrolysis temperature between 300 °C and 800 °C on the chemical and physical properties of biochar obtained from biosolids via MWAP. Preliminary phosphorus adsorption tests were carried out with the biochar produced from biosolids. This research demonstrated that pyrolysis temperature affects biochar specific surface area, ash and volatiles content, but does not impact heavily on the pH, chemical composition and crystalline phases of the resultant biochar. Biochar yield decreases as the pyrolysis temperature increases. Phosphorus adsorption capacity of biochar was approximately around 15 mg/g of biochar. Biochar resulting from MWAP is a potential candidate for land application with an important role in water and nutrient retention, due to the high surface area.

Estimated cost savings from reducing errors in the preparation of sterile doses of medications.

BACKGROUND: Preventing intravenous (IV) preparation errors will improve patient safety and reduce costs by an unknown amount. OBJECTIVE: To estimate the financial benefit of robotic preparation of sterile medication doses compared to traditional manual preparation techniques. METHODS: A probability pathway model based on published rates of errors in the preparation of sterile doses of medications was developed. Literature reports of adverse events were used to project the array of medical outcomes that might result from these errors. These parameters were used as inputs to a customized simulation model that generated a distribution of possible outcomes, their probability, and associated costs. RESULTS: By varying the important parameters across ranges found in published studies, the simulation model produced a range of outcomes for all likely possibilities. Thus it provided a reliable projection of the errors avoided and the cost savings of an automated sterile preparation technology. The average of 1,000 simulations resulted in the prevention of 5,420 medication errors and associated savings of $288,350 per year. The simulation results can be narrowed to specific scenarios by fixing model parameters that are known and allowing the unknown parameters to range across values found in previously published studies. CONCLUSIONS: The use of a robotic device can reduce health care costs by preventing errors that can cause adverse drug events.

ASHP National Survey of Pharmacy Practice in Hospital Settings: Operations and Technology - 2023.

PURPOSE: Results of the 2023 ASHP National Survey of Pharmacy Practice in Hospital Settings are presented. METHODS: Pharmacy directors at 1,497 general and children's medical-surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online using Qualtrics. IQVIA supplied data on hospital characteristics; the survey sample was drawn from IQVIA's hospital database. RESULTS: The response rate was 21.6%. Inpatient pharmacists independently prescribe medications in 26.7% of hospitals. Advanced analytics are used in 5.7% of hospitals. Basic analytics are used in 87.3% of hospitals. Pharmacists work in ambulatory or primary care clinics in 54.2% of hospitals operating outpatient clinics. Most hospitals (86.1%) use automated dispensing cabinets as the primary method of maintenance dose distribution. Machine-readable coding is used in 73.6% of hospitals to verify doses during dispensing in the pharmacy. Autoverification functionality in the electronic health record system is used in 73.4% of hospitals. Most hospitals report some integration of pharmacy services to optimize patient care transitions (60.0%), while 24.9% report no integration. Traditional technician activities still predominate, but more advanced roles are emerging. Technologies to assist sterile product preparation are used in 62.8% of hospitals. CONCLUSION: Drug distribution continues to trend toward decentralized models with medications available closer to patients. Technologies are enabling this transition to occur without a significant negative impact on patient safety. The pharmacy workforce is stable, and more advanced responsibilities are being assigned to pharmacy technicians, enabling pharmacists to increase their clinical role.

Pysanky to Microfluidics: An Innovative Wax-Based Approach to Low Cost, Rapid Prototyping of Microfluidic Devices.

A wax-based contact printing method to create microfluidic devices is demonstrated. This printing technology demonstrates a new pathway to rapid, cost-effective device prototyping, eliminating the use of expensive micromachining equipment and chemicals. Derived from the traditional Ukrainian Easter egg painting technique called "pysanky" a series of microfluidic devices were created. Pysanky is the use of a heated wax stylus, known as a "kistka", to create micro-sized, intricate designs on the surface of an egg. The proposed technique involves the modification of an x-y-z actuation translation system with a wax extruder tip in junction with Polydimethysiloxane (PDMS) device fabrication techniques. Initial system optimization was performed considering design parameters such as extruder tip size, contact angle, write speed, substrate temperature, and wax temperature. Channels created ranged from 160 to 900 µm wide and 10 to 150 µm high based upon system operating parameters set by the user. To prove the capabilities of this technology, a series of microfluidic mixers were created via the wax technique as well as through traditional photolithography: a spiral mixer, a rainbow mixer, and a linear serial dilutor. A thermo-fluidic computational fluid dynamic (CFD) model was generated as a means of enabling rational tuning, critical to the optimization of systems in both normal and extreme conditions. A comparison between the computational and experimental models yielded a wax height of 57.98 µm and 57.30 µm, respectively, and cross-sectional areas of 11,568 µm2 and 12,951 µm2, respectively, resulting in an error of 1.18% between the heights and 10.76% between the cross-sectional areas. The device's performance was then compared using both qualitative and quantitative measures, considering factors such as device performance, channel uniformity, repeatability, and resolution.

Contrast enhanced transesophageal echocardiography in patients with atrial fibrillation referred to electrical cardioversion improves atrial thrombus detection and may reduce associated thromboembolic events.

AIMS: Transesophageal echocardiography (TEE) is the gold standard for the detection of thrombi in patients with atrial fibrillation (AF) before undergoing early electrical cardioversion (CV). However, TEE generates inconclusive results in a considerable number of patients. This study investigated the influence of contrast enhancement on interpretability of TEE for the detection of left atrial (LA) thrombi compared to conventional TEE and assessed, whether there are differences in the rate of thromboembolic events after electrical cardioversion. METHODS: Of 180 patients with AF (51 females, 65.2±13 years) who were referred to CV, 90 were examined with native imaging and contrast enhancement within the same examination (group 1), and 90 were examined with native TEE alone and served as control (group 2). Cineloops of the multiplane examination of the LA and LA appendage (LAA) were stored digitally before and, in group 1, after intravenous bolus application of a transpulmonary contrast agent. Images of group 1 were assessed offline and the diagnosis of LA thrombi was made semi-quantitatively: 1= thrombus present; 2=inconclusive result; 3=no thrombus. The presence of spontaneous echocontrast (SEC) was registered and flow velocity in the LA appendage (LAA-flow) was measured. All patients in whom CV was performed were followed up for 1 year or until relapse of AF. CV related adverse events were defined as any thromboembolic event within 1 week after CV. RESULTS: No serious adverse events occurred during TEE and contrast enhanced imaging. In group 1 atrial thrombi were diagnosed in 14 (15.6%) during native and in 10 (11.1%) patients during contrast enhanced imaging (p<0.001). Of the 10 patients with thrombi in the contrast TEE group, 7 revealed a decreased LAA-flow (≤0,3m/s) and 8 showed moderate or marked SEC. Uncertain results were significantly more common during native imaging than with contrast enhanced TEE (16 vs. 5 patients, p<0.01). Thrombi could definitely be excluded in 60 (66.7%) during conventional and in 75 patients (83.3%) during contrast enhanced TEE (p<0.01). CV was performed subsequently after exclusion of thrombi and at the discretion of the investigator. In group 1, 74 patients (82.2%) were cardioverted and no patient suffered a CV related complication (p=0.084). In group 2, 76 patients (84.4%) underwent CV, of whom 3 suffered a thromboembolic complication after CV (2 strokes, 1 peripheral embolism). CONCLUSION: In patients with AF planned for CV contrast enhancement renders TEE images more interpretable, facilitates the exclusion of atrial thrombi and may reduce the rate of embolic adverse events.

Modelling and dynamic simulation of struvite precipitation from source-separated urine.

A model of a mixed-mode nutrient recovery reactor is developed for a urine feed, incorporating complex solution thermodynamics, dynamic conservation relations and a power-law kinetic expression for crystal growth from seed crystals. Simulations at nominal operating conditions predict phosphorus recoveries greater than 99%, based on existing process kinetic parameters and operating conditions employed in previously published studies. The overall rate of nutrient recovery depends on the saturation index of the precipitating solid, the available surface area for mass transfer and the feed rate of the limiting constituent ion. Under the conditions considered, the nutrient feed rate appears to be the limiting factor for precipitation. Simulations demonstrate that diurnal feed flow variations of ±50% have a small effect on the rate of nutrient recovery. Overall, the study shows that valuable insights are gained in relation to process performance predictions, which should lead to more confident process design, operation and control.

Modelling and experimentation of a continuous nutrient recovery reactor - an assessment of mixing on reactor operation.

Phosphorus recovery from human waste will help assure global food security, reduce environmental impact, and ensure effective stewardship of this limited and valuable resource. This can be accomplished by the precipitation of struvite (MgNH4PO4·6H2O) in a two-zone reactor, continuously fed with nutrient-rich hydrolysed urine and a magnesium solution. The solid struvite crystals are periodically "harvested", removing accumulated crystal mass - and therefore recovered nutrients - from the process, and the operating campaign can, in principle, be continuously operated in a batch-continuous operating mode. A previously developed process model is augmented, incorporating two well-mixed volumes (upper zone and lower zone) that are coupled by intermixing forward and back flows. The intermixing back flow is parametrised and, therefore, adjusted for analysis. Crystal linear growth rate is modelled by a simple power-law kinetic, driven by the nutrient solution's saturation index (SI) of struvite. The instantaneous mass transfer rate of struvite constituents from liquid to solid phase is predicted, using the total interfacial area of the crystal population exposed to the well-mixed solution. This model describes a 12-L, laboratory reactor operated in the hybrid batch-continuous mode, although larger reactors could easily be accommodated, subject to their mixing behaviours. Experiments were performed at a 10-hour hydraulic residence time (HRT), which, importantly, is based on the volume of the well-mixed lower zone, since this is the volume of liquid that actively interacts with the suspended struvite crystals. The Mg/P feed molar ratio was varied (0.34, 0.64 and 1.29) to assess Mg feed rate-limiting behaviour. The concentration profiles of elemental P and Mg agree with experimentation, while P and Mg composition in the solid and X-ray diffraction support the production of struvite.

ASHP National Survey of Pharmacy Practice in Hospital Settings: Workforce - 2022.

PURPOSE: Results of the 2022 ASHP National Survey of Pharmacy Practice in Hospital Settings are presented. METHODS: Pharmacy directors at 1,498 general and children's medical/surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online. IQVIA supplied data on hospital characteristics; the survey sample was drawn from IQVIA's hospital database. RESULTS: The response rate was 23.7%. Inpatient pharmacists independently prescribe in 27.1% of hospitals. Advanced analytics are used in 8.7% of hospitals. Pharmacists work in ambulatory or primary care clinics in 51.6% of hospitals operating outpatient clinics. Some level of pharmacy service integration is reported in 53.6% of hospitals. More advanced pharmacy technician roles are emerging. For health systems offering hospital at home services, 65.9% of pharmacy departments are involved. Shortages of pharmacists and technicians were reported but are more acute for pharmacy technicians. Aspects of burnout are being measured in 34.0% of hospitals, and 83.7% are attempting to prevent and mitigate burnout. The average number of full-time equivalents per 100 occupied beds is 16.9 for pharmacists and 16.1 for pharmacy technicians. CONCLUSION: Health-system pharmacies are experiencing workforce shortages; however, these shortages have had limited impact on budgeted positions. Workforce challenges are influencing the work of pharmacists and pharmacy technicians. Adoption of practice advancement initiatives has continued the positive trend from past years despite workforce issues.

ASHP National Survey of Pharmacy Practice in Hospital Settings: Clinical services and workforce-2021.

PURPOSE: Results of the 2021 ASHP National Survey of Pharmacy Practice in Hospital Settings are presented. METHODS: Pharmacy directors at 1,498 general and children's medical/surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online. IQVIA supplied data on hospital characteristics; the survey sample was drawn from IQVIA's hospital database. RESULTS: The response rate was 21.9%. Pharmacists are routinely assigned to a majority of patients at least 8 hours per day, 5 days per week in 70.4% of hospitals. This is an increase from 60.8% in 2018 and has steadily increased over the past decade. Pharmacists independently prescribe medications pursuant to a diagnosis in 30.9% of hospitals, an increase from 21.1% in 2020. Pharmacists have prescribing authority in 67% of health-system ambulatory clinics and can recommend or schedule pharmacogenomics testing for drug and dosage selection in 11.4% of hospitals, an increase from 5.4% in 2019. Pharmacists are using electronic methods in 82.5% of hospitals to collect information for monitoring medication therapy. Shortages of entry-level pharmacy technicians are acute, with 73.4% of survey respondents reporting a shortage. Technician shortages have affected pharmacy operations and have prompted new recruitment and retention strategies. CONCLUSION: Despite workforce challenges, clinical pharmacy services continue to expand to cover increasing numbers of patients with medication management services in both the inpatient and outpatient settings. The use of data analytics and pharmacy technicians has contributed to this evolution. Addressing the workforce challenges will be critical to sustain this progress.

ASHP national survey of pharmacy practice in hospital settings: Impact of COVID-19 pandemic on pharmacy operations-2020.

PURPOSE: Results of the 2020 ASHP national survey of pharmacy practice in hospital settings pertaining to pharmacy operational changes implemented in response to the coronavirus disease 2019 (COVID-19) pandemic are presented. METHODS: Pharmacy directors at 1,437 general and children's medical/surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online. RESULTS: The response rate was 18.7%. Seventy-three percent of hospitals implemented changes to hospital units, including 46% that increased intensive care unit bed capacity; 94% made changes to pharmacy supply chain acquisition, changes to products, and/or increased inventory. Staffing changes were implemented by 69% of hospitals, with the most common being staffing reductions (55%) and salary reductions (16%). Medication-use changes were implemented by 86% of hospitals, with treatment guidelines for COVID-19 treatment (79%) and opening compassionate use or investigational drug studies (55%) being the most common. Changes in sterile compounding processes were implemented by 84% of hospitals. Personal protective equipment (PPE) shortages led to 71% of hospitals modifying PPE use standards in sterile compounding. Eighty-seven percent of hospitals changed operational activities, such as changing medication return practices (56%), medication reconciliation processes (46%), intravenous medication recycling (38%), and discharge counseling (37%). Hospitals experienced shortages of many medications, including albuterol inhalers (60%), sedatives and anesthetic agents (58%), neuromuscular blockers (43%), corticosteroids (34%), cardiovascular agents (24%), investigational agents (24%), and dialysis solutions (6%). CONCLUSION: The pharmacy profession responded to myriad threats to operations and patient care during the COVID-19 pandemic in 2020.

ASHP national survey of pharmacy practice in hospital settings: Dispensing and administration-2020.

PURPOSE: Results of the 2020 ASHP national survey of pharmacy practice in hospital settings are presented. METHODS: Pharmacy directors at 1,437 general and children's medical/surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online. IQVIA supplied data on hospital characteristics; the survey sample was drawn from the IQVIA hospital database. RESULTS: The response rate was 18.7%. Almost all hospitals (92.5%) have a method for pharmacists to review medication orders on demand. Most hospitals (74.5%) use automated dispensing cabinets (ADCs) as their primary method for drug distribution. A third of hospitals use barcodes to verify doses during dispensing in the pharmacy and to verify ingredients when intravenous medications are compounded. More than 80% scan barcodes when restocking ADCs. Sterile workflow management technology is used in 21.3% of hospitals. Almost three-quarters of hospitals outsource some sterile preparations. Pharmacists can independently prescribe in 21.1% of hospitals. Pharmacist practice in ambulatory clinics in 46.2% of health systems and provide telepharmacy services in 28.4% of health systems. CONCLUSION: Pharmacists continue their responsibility in their traditional role in preparation and dispensing of medications. They have successfully employed technology to improve safety and efficiency in performance of these duties and have employed emerging technologies to improve the safety, timeliness, and efficiency of the administration of drugs to patients. As pharmacists continue to expand their role to all aspects of medication use, new opportunities highlighted in ASHP's Practice Advancement Initiative 2030 have been identified.

An Integrated Centrifugal Degassed PDMS-Based Microfluidic Device for Serial Dilution.

We propose an integrated serial dilution generator utilizing centrifugal force with a degassed polydimethylsiloxane (PDMS) microfluidic device. Using gas-soluble PDMS as a centrifugal microfluidic device material, the sample can be dragged in any arbitrary direction using vacuum-driven force, as opposed to in a single direction, without adding further actuation components. The vacuum-driven force allows the device to avoid the formation of air bubbles and exhibit high tolerance in the surface condition. The device was then used for sample metering and sample transferring. In addition, centrifugal force was used for sample loading and sample mixing. In this study, a series of ten-fold serial dilutions ranging from 100 to 10-4 with about 8 µL in each chamber was achieved, while the serial dilution ratio and chamber volume could easily be altered by changing the geometrical designs of the device. As a proof of concept of our hybrid approach with the centrifugal and vacuum-driven forces, ten-fold serial dilutions of a cDNA (complementary DNA) sample were prepared using the device. Then, the diluted samples were collected by fine needles and subject to a quantitative polymerase chain reaction (qPCR), and the results were found to be in good agreement with those for samples prepared by manual pipetting.

Adjuvant external beam radiation for medullary thyroid carcinoma.

BACKGROUND: Adjuvant radiation is rarely used to treat medullary thyroid carcinoma (MTC). We hypothesized that external beam radiation therapy (EBRT) would improve overall survival (OS) in MTC patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database identified patients who underwent total thyroidectomy and lymph nodes excision for MTC between 1988 and 2004. The Kaplan-Meier method was used for univariate comparisons of OS. Multivariate Cox proportional hazards models controlled for gender, age, lymph node status, tumor size, extent of disease, and EBRT. RESULTS: After 12 years, EBRT did not significantly improve OS (log rank, P < 0.14). In node-positive patients, univariate analysis demonstrated an OS benefit with EBRT (log rank, P < 0.05). In a multivariate model of node-positive patients, only increasing age (P < 0.001) and tumor size (P < 0.001) significantly influenced OS. CONCLUSIONS: The OS benefit attributed to EBRT in node-positive patients by univariate analysis could not be duplicated when controlling for known prognostic factors.

An evaluation of lymph node yield and lymph node ratio in well-differentiated thyroid carcinoma.

It is unknown whether the number of lymph nodes harvested (lymph node yield, LNY) or the proportion of metastatic lymph nodes resected (metastatic lymph node ratio, MLNR) influence survival in well-differentiated thyroid carcinoma (WDTC). We hypothesized that overall survival in WDTC is influenced by the LNY and MLNR. We used the Surveillance, Epidemiology, and End Results database to identify all patients with primary, nonmetastatic WDTC who underwent thyroidectomy with at least one lymph node removed between 1988 and 2004. Kaplan-Meier survival curves for LNY and MLNR were compared using the log rank test. Multivariate Cox proportional hazards models included tumor and patient-specific factors. WDTC patients that met entry criteria totaled 9926. In the univariate model, LNY and MLNR had a significant impact on survival (P < 0.001). In multivariate analysis, increasing LNY was associated with poorer survival in all patients (P = 0.001) and node-negative patients (P = 0.03), but not for node-positive patients (P = 0.27). MLNR did not influence survival in node-positive patients (P = 0.84). Among patients with WDTC treated with thyroidectomy and lymphadenectomy, increasing LNY and MLNR were associated with decreased survival. The decrease in survival associated with increasing LNY, even in node-negative patients, indicates that nodal understaging is inconsequential to WDTC survival.

ASHP national survey of pharmacy practice in hospital settings: Prescribing and transcribing-2019.

PURPOSE: Results of the 2019 ASHP national survey of pharmacy practice in hospital settings are presented. METHODS: Pharmacy directors at 4,863 general and children's medical/surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online, using an online survey application. IQVIA supplied data on hospital characteristics; the survey sample was drawn from the IMS Health hospital database. RESULTS: The response rate was 10.8%. Pharmacists are increasingly managing medication use in the areas of vancomycin therapy, antibiotic selection and dosing, and anticoagulation. Electronic health record (EHR) decision support is guiding prescribing, and nearly 50% of hospitals are customizing drug warnings. Adoption of compounding technology continues, with 43.6% of hospitals using technology in their sterile compounding processes. Nearly half of hospitals have active opioid stewardship programs, and pharmacists are leading these efforts. Specialty pharmacy operations are growing in health systems. Human resource commitments to support new services are increasing; however, vacancy rates for technicians are challenging. Staff credentialing continues to expand for pharmacist and technicians. CONCLUSION: Pharmacists continue to assume greater responsibility for writing medication orders, dosing, ordering laboratory tests, and monitoring outcomes. Health-system pharmacists are taking a leading role in addressing the opioid crisis, advancing safety in compounded sterile preparations through adoption of intravenous workflow technologies, and optimizing EHR applications to leverage clinical decision support tools to improve the safe prescribing and use of medications.

Tumour-derived prostaglandin E and transforming growth factor-beta synergize to inhibit plasmacytoid dendritic cell-derived interferon-alpha.

In previous studies we reported that plasmacytoid dendritic cells (PDC) infiltrating head and neck cancer tissue are functionally impaired, but the molecular basis for the functional deficiency remained unclear. Here we demonstrate that tumour-derived prostaglandin E2 (PGE(2)) and transforming growth factor-beta (TGF-beta) increase interleukin-8 (IL-8) but synergistically inhibit interferon-alpha (IFN-alpha) and tumour necrosis factor (TNF) production of Toll-like receptor 7 (TLR7)- and Toll-like receptor 9 (TLR9)-stimulated PDC. The inhibitory effect of PGE(2) could be mimicked by the induction of cyclic AMP (cAMP) and by inhibitors of cyclooxygenase. The contribution of tumour-derived TGF-beta was confirmed by the TGF-beta antagonist SB-431542. Suppression of tumour-derived PGE(2) and TGF-beta restored TLR-induced IFN-alpha production of PDC. Additionally, PGE(2)- and TGF-beta-treated PDC display a 'tolerogenic' phenotype because of a downregulation of CD40 accompanied by an upregulation of CD86. Finally, in TLR-stimulated PDC, PGE(2) and TGF-beta reduce the CCR7:CXCR4 ratio, suggesting that PDC are impaired in their ability to migrate to tumour-draining lymph nodes but are retained in stromal cell-derived factor 1 (SDF-1)-expressing tissues. Based on these data, cyclooxygenase inhibitors and TGF-beta antagonists may improve TLR7- and TLR9-based tumour immunotherapy.