Search

Hepatitis B virus (HBV) can rapidly replicate in the hepatocytes after transmission, leading to chronic hepatitis, liver cirrhosis and eventually hepatocellular carcinoma. Interferon-α (IFN-α) is included in the standard treatment for chronic hepatitis B (CHB). However, this therapy causes serious side effects. Delivering IFN-α selectively to the liver may enhance its efficacy and safety. Imiquimod (IMQ), a Toll-Like Receptor (TLR) 7 agonist, stimulates the release of IFN-α that exhibits potent antiviral activity. However, the poor solubility and tissue selectivity of IMQ limits its clinical use. Here, we demonstrated the use of lipid-based nanoparticles (LNPs) to deliver IMQ and increase the production of IFN-α in the liver. We encapsulated IMQ in two liver-targeted LNP formulations: phospholipid-free small unilamellar vesicles (PFSUVs) and DSPG-liposomes targeting the hepatocytes and the Kupffer cells, respectively. In vitro drug release/retention, in vivo pharmacokinetics, intrahepatic distribution, IFN-α production, and suppression of serum HBV surface antigen (HBsAg) were evaluated and compared for these two formulations. PFSUVs provided95% encapsulation efficiency for IMQ at a drug-to-lipid ratio (D/L) of 1/20 (w/w) and displayed stable drug retention in the presence of serum. DSPG-IMQ showed 79% encapsulation of IMQ at 1/20 (D/L) and exhibited ∼30% burst release when incubated with serum. Within the liver, PFSUVs showed high selectivity for the hepatocytes while DSPG-liposomes targeted the Kupffer cells. Finally, in an experimental HBV mouse model, PFSUVs significantly reduced serum levels of HBsAg by 12-, 6.3- and 2.2-fold compared to the control, IFN-α, and DSPG-IMQ groups, respectively. The results suggest that the hepatocyte-targeted PFSUVs loaded with IMQ exhibit significant potential for enhancing therapy of CHB.

Disease recurrence is common following prostatectomy in patients with localised prostate cancer with high-risk features. Although androgen deprivation therapy increases the rates of organ-confined disease and negative surgical margins, there is no significant benefit on disease recurrence. Multiple lines of evidence suggest that (Fibroblast Growth Factor/Fibroblast Growth Factor Receptor) FGF/FGFR-signalling is important in supporting prostate epithelial cell survival in hostile conditions, including acute androgen deprivation. Given the recent availability of oral FGFR inhibitors, we investigated whether combination therapy could improve tumour response in the neo-adjuvant setting.We conducted an open label phase II study of the combination of erdafitinib (3 months) and androgen deprivation therapy (4 months) in men with localised prostate cancer with high-risk features prior to prostatectomy using a Simon's 2 stage design. The co-primary endpoints were safety and tolerability and pathological response in the prostatectomy specimen. The effect of treatment on residual tumours was explored by global transcriptional profiling with RNA-sequencing.Nine patients were enrolled in the first stage of the trial. The treatment combination was poorly tolerated. Erdafitinib treatment was discontinued early in six patients, three of whom also required dose interruptions/reductions. Androgen deprivation therapy for 4 months was completed in all patients. The most common adverse events were hyperphosphataemia, taste disturbance, dry mouth and nail changes. No patients achieved a complete pathological response, although patients who tolerated erdafitinib for longer had smaller residual tumours, associated with reduced transcriptional signatures of epithelial cell proliferation.Although there was a possible enhanced anti-tumour effect of androgen deprivation therapy in combination with erdafitnib in treatment naïve prostate cancer, the poor tolerability in this patient population prohibits the use of this combination in this setting.

We sought to determine if using the ACR TI-RADS ultrasound score combined with the Bethesda diagnosis can help augment thyroid cancer risk estimation.TI-RADS scores and Bethesda diagnoses were collected for patients treated in our center who had undergone thyroidectomy. Data from 186 patients with both TI-RADS scores and Bethesda diagnosis, and Bethesda diagnosis alone, were analyzed by multivariable regression analysis and observed for whether the pathology was benign or malignant.The regression analysis model showed that as the TI-RADS score increases, the odds of malignancy increases as well. The predictive value of the odds of malignancy in a thyroid nodule using both Bethesda diagnosis and TI-RADS score together was more powerful than the odds given using the Bethesda diagnosis alone.Our model shows that the ACR TI-RADS score may assist with preoperative decision-making for patients with cytologically indeterminate thyroid nodules when combined with Bethesda diagnosis.

While the installation of complex genetic circuits in microorganisms is relatively routine, the synthetic biology toolbox is severely limited in plants. Of particular concern is the absence of combinatorial analysis of regulatory elements, the long design-build-test cycles associated with transgenic plant analysis, and a lack of naming standardization for cloning parts. Here, we use previously described plant regulatory elements to design, build, and test 91 transgene cassettes for relative expression strength. Constructs were transiently transfected into

Nanomedicines including lipid- and polymer-based nanoparticles and polymer-drug conjugates enable targeted drug delivery for the treatment of numerous diseases. Quantitative analysis of components in nanomedicines is routinely performed to characterize the products to ensure quality and property consistency but has been mainly focused on the active pharmaceutical ingredients (APIs) in academic publications. It has been increasingly recognized that excipients in nanomedicines are critical in determining the product quality, stability, consistency, and safety. APIs are often analyzed by high-performance liquid chromatography (HPLC), and it would be convenient if the same method can be applied to excipients to robustly quantify all components in nanomedicines. Here, we report the development of a HPLC method that combined an evaporative light scattering (ELS) detector with an UV-vis detector to simultaneously analyze drugs and excipients in nanomedicines. This method was tested on diverse nanodrug delivery systems, including a niosomal nanoparticle encapsulating a phytotherapeutic, a liposome encapsulating an immune boosting agent, and a PEGylated peptide. This method can be utilized for a variety of applications, such as monitoring drug loading, studying drug release, and storage stability. The information obtained from the analyses is of importance for nanomedicine formulation development.

Microbial genetic manipulation requires access to engineerable plasmids that can be programmed to perturb genes, pathways and genomes. The extensive repertoire of plasmids available for model microbes, such asEscherichia coli, has facilitated fundamental biology studies and synthetic biology applications. However, the scarcity of plasmids for non-model microbes hinders efforts to broaden our biological knowledge and constrains the development of biotechnological solutions. In this study, we introduce a molecular toolkit and multiplexed screen to evaluate functional plasmids in non-model microbes. We constructed a collection of genetic parts consisting of 22 origins of replication (ORIs), 20 antibiotic selectable markers, and 30 molecular barcodes, which can be assembled combinatorially to create a library of plasmids trackable by next-generation DNA sequencing. We demonstrate our approach by delivering a pooled library of 22 ORIs to 12 bacterial species including extremophiles, electroactive bacteria and bioproduction strains. We report, for the first time, DNA delivery by conjugation and functional ORIs forHalomonas alkaliphila, Halomonas neptunia,andShewanella electrodiphila. Furthermore, we expand the list of functional ORIs forDuganella zoogloeoides,Pseudomonas alcaliphila,Shewanella oneidensisandShewanella putrefaciens. This screen provides a scalable high-throughput system to rapidly build and identify functional plasmids to establish genetic tractability in non-model microbes.

Background Inaccurate penicillin allergy labels lead to inappropriate antibiotic prescriptions and harmful patient consequences. System-wide efforts are needed to remove incorrect penicillin allergy labels, but more health services research is required on how to best deliver these services. Methods Data was extracted from five hospitals in Vancouver, British Columbia, Canada from October 2018-May 2022. The primary outcomes of this study were to outline de-labelling protocol designs, identify the roles of various healthcare professionals in de-labelling protocols and identify rates of de-labelling penicillin allergies and associated adverse events at various institutions. Our secondary outcome was to describe de-labelling rates for special populations, including pediatric, obstetric and immunocompromised subpopulations. To achieve these outcomes, participating institutions provided their de-labelling protocol designs and data on program participants. Protocols were then compared to find common themes and differences. Furthermore, adverse events were reviewed and percentages of patients de-labelled at each institution and in total were calculated. Results Protocols demonstrated a high level of variability, including different methods of participant identification, risk-stratification and roles of providers. All protocols used oral and direct oral challenges, heavily involved pharmacists and had physician oversight. Despite the differences, of the 711 patients enrolled in all programs, 697 (98.0%) were de-labelled. There were 9 adverse events (1.3%) with oral challenges with mainly minor symptoms. Conclusions Our data demonstrates that de-labelling programs effectively and safely remove penicillin allergy labels, including pediatric, obstetric and immunocompromised patients. Consistent with current literature, most patients with a penicillin allergy label are not allergic. De-labelling programs could benefit from increasing clinician engagement by increasing accessibility of resources to providers, including guidance for de-labelling of special populations.

PDF file - 6KB, Table S1. List of genes used for geneset enrichment analysis.

PDF file - 148KB, Figure S1. Mean + SEM concentration of indicated steroids measured in the conditioned media derived from BPH, hormone na�ve CaP or HRPC when cultured in the presence of cholesterol, progesterone, DHEA or testosterone at a concentration of 10 ng/ml for 96 hr.

Poorly water-soluble small hydrophobic compounds can be conjugated to a hydrophilic polymer such as methoxypolyethylene glycol (mPEG) to form amphiphilic prodrugs that can self-assemble into nanoparticles (NPs) with increased aqueous solubility, prolonged circulation, and improved delivery. There have been numerous reports utilizing this strategy to improve delivery of small molecule drugs, but few reports take systematic, structure-activity relationship (SAR)-based approaches to develop optimal prodrug conjugates. Additionally, it is important to study interplay of different components within the conjugate, such as polymer molecular weight (M.W.) and linker to obtain optimal efficacy and safety. In this study, we developed a click chemistry platform to conjugate mPEG of three different M.W. (low: 550 Da; medium: 2000 Da; high: 5000 Da) to a small molecular anti-tumor drug, gambogic acid (GA)

Background Guidelines recommend patient health-related information be written at or below the sixth-grade level. This study evaluates the readability level and quality of online appendectomy patient education materials. Methods Webpages were evaluated using seven readability formulae: Flesh-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), Coleman-Liau Index (CLI), Automated Readability Index (ARI), Simple Measure of Gobbledygook (SMOG), Flesch Reading Ease (FRE), and New Dale-Chall (NDC). Two evaluators assessed quality using the Brief DISCERN tool. Results Thirty seven webpages were analyzed. The mean readability scores were: FKGL = 9.11, GFI = 11.82, CLI = 10.84, ARI = 7.99, SMOG = 11.88, FRE = 51.17, and NDC = 5.48. 6 of the 7 readability formulae indicate that the materials were written at too high a level. The average Brief DISCERN score was 17.81, indicating good quality. Conclusions Readability levels for online appendectomy patient education materials are higher than recommended but are of good quality. Authors of such materials should not only provide good quality information but also ensure readability.

Many medicines are only available in solid dosage forms suitable for adults, and extemporaneous compounding is required to prepare formulations for children. However, this common practice often results in inaccurate dosing and unpleasant taste, reducing the medication adherence. Here, we report the development of a new method to prepare and compound child-friendly oral formulations based on a liposomal multilamellar vesicle (MLV) platform. MLVs composed of a phospholipid (DSPC) and cholesterol (55/45, molar ratio) were prepared using the standard thin film hydration method with 300 mM citric acid (pH 2), followed by an addition of aqueous sodium carbonate to adjust the exterior pH to 8-10 for creating a transmembrane pH gradient. Weak-base drugs, such as chloroquine (CQ) and hydroxychloroquine (HCQ), could be actively and completely loaded into the MLVs at a drug-to-lipid ratio of 15-20 wt%. This technique formulated weak-base drugs from the powder or tablet form into a liquid preparation, and the complete drug encapsulation would prevent contact between the drug molecules and the taste buds. The gradient MLV formulation could be preserved by lyophilization and stored at room temperature for at least 8 weeks. Upon reconstitution with water, the MLV formulation could completely encapsulate CQ at 20 wt%, which was comparable to the freshly prepared MLVs. The CQ-loaded MLV formulation could be stored at 4 °C for 2 weeks without drug leakage. In vitro release studies indicated that MLV could retain CQ in the simulated saliva, but released up to 50% and 30% of the drug in the simulated gastric and intestinal fluids, respectively. The orally delivered MLV-CQ formulation displayed higher CQ absorption in mice, with a 2-fold increase in the area under the curve (AUC) of the plasma profile compared to CQ solution. Our data suggest that the new MLV method could serve as a platform to prepare child-friendly oral formulation for weak-base drugs.

Primary open-angle glaucoma (POAG) is currently treated with a variety of surgical and non-surgical approaches. Minimally invasive glaucoma surgery (MIGS) involves several devices and procedures that lower intraocular pressure (IOP) by increasing aqueous outflow. The first laser-based MIGS procedure, Excimer Laser Trabeculostomy (ELT), has emerged as a safe and effective treatment option. This article reviews ELT within the context of alternative MIGS procedures and focuses on the historical development of ELT, principles and techniques of the ELT procedure, safety and efficacy data, comparison to other outflow procedures, and future augmentations to expand the use of ELT. Performed alone or as an adjunct to cataract surgery, ELT has minimal complications and has shown long-term effectiveness in lowering intraocular pressure in thousands of patients. The non-thermal laser-tissue interactions of excimer lasers minimize peripheral tissue damage and ensure outflow channel patency without requiring foreign body implants or creating blebs. The development of 2D optical and 3D optical coherence tomography (OCT) guidance systems will eliminate the need for a goniolens to visualize angle structures and enable thousands more surgeons to perform ELT in the future.

With the advent of plant synthetic biology, there is an urgent need to develop plant-based systems that are able to effectively enhance the speed of design-build-test cycles to screen large numbers of synthetic constructs. Thus far, protoplasts have served to fill this need, with cell suspension cultures serving as the primary source tissue to enable high-throughput protoplast experimentation. The possibility to use low-cost food-grade enzymes for cell wall digestion along with polyethylene glycol (PEG)-mediated transfection makes protoplasts particularly suited to automation and high-throughput screening. In other systems for which synthetic biology is well established (model bacteria and yeast), libraries of components, i.e., promoters, 5' untranslated regions, 3' untranslated regions, terminators, and transcription factors, serve as the basis for the design of complex genetic circuits. In order for synthetic biology to make similar strides in plant biology, well-characterized libraries of functional genetic parts for plants are required, necessitating the need for high-throughput protoplast assays.In this chapter, we describe an optimized method for the preparation of soybean (Glycine max ) dark-grown cell suspension cultures, followed by protoplast isolation, automated transfection , and subsequent screening.

Compact sources in the mid-wave infrared (MWIR) are needed for applications ranging from spectroscopy to free-space communication. Ultrathin incandescent metasurfaces are promising candidates, offering the possibility to tune the emission spectrum, directivity, and modulation speed. However, control over polarization remains a challenge, especially when it comes to the emission of circularly polarized light. Here, we report the emission of polarized MWIR radiation from a 700 nm thick incandescent chiral metasurface. The degree of polarization is above 0.5 with degree of circular polarization of 0.38 at 5 µm. The metasurface is heated by the Joule effect, and the emission can be modulated beyond 10 MHz. This could enable detection techniques that use polarization as an additional degree of freedom.

In March 2020, British Columbia issued Risk Mitigation Guidance (RMG) to support prescribing of pharmaceutical alternatives to illicit drugs, in order to reduce risk for COVID-19, overdose, and withdrawal among people who use drugs. This study evaluated factors associated with 60-day adherence to novel opioid alternatives prescribed at an inner-city health centre in Victoria, Canada.A chart review was conducted to collect data on sociodemographic information, medical histories, and follow-up services among all clients prescribed novel opioid alternatives from March 2020-August 2020 (n = 286). Bivariable and multivariable regression were used to identify independent and adjusted factors associated with 60-day adherence.Overall, 77% of 286 clients were still receiving opioids after 60 days of follow-up. Medications included hydromorphone (n = 274), sustained-release oral morphine (n = 2), and oxycodone (n = 9). The adjusted odds of 60-day adherence to novel opioid alternatives were significantly higher for those receiving a mental health medication (aOR = 3.49, 95%CI = 1.26, 11.00), a higher maximum daily dosage of RMG prescriptions (aOR = 1.03 per mg increase, 95%CI = 1.01, 1.04), and those with continuous receipt of OAT (aOR = 6.25, 95%CI = 2.67, 15.90).Higher dosages and co-prescription of mental health medications and OAT may help support better adherence to this form of prescriber-based "safer supply". Further work is needed to identify optimal prescribing practices and the longer term impacts of differing implementation scenarios.

High-dose methotrexate (HDMTX) is a commonly used treatment for hematologic malignancies involving the central nervous system. Two case reports described possible delayed methotrexate clearance in patients receiving concurrent levetiracetam, while a retrospective cohort study did not find this association. The objective of this single-center, retrospective case-control study of 121 patients who received their first cycle of HDMTX was to investigate the association between HDMTX clearance time and concomitant levetiracetam use. The most common diagnosis was primary central nervous system lymphoma (47.9%). The mean HDMTX dose was 4601 mg/m2 (standard deviation [SD], 2052.6 mg/m2 ). Concurrent levetiracetam was administered in 30 of 121 patients (24.8%), with a mean total daily levetiracetam dose of 1434.4 mg (SD, 622.9 mg; range, 900-3000 mg). Baseline characteristics were similar between patients who received concomitant levetiracetam and those who did not. The mean time to methotrexate clearance was 82.5 hours (SD, 51.2; 95% confidence interval, 69.4-95.7) in the concomitant levetiracetam group and 72.4 hours (SD, 31.2; 95% confidence interval, 61.7-83.0) in the nonlevetiracetam group, which was not significantly different (P > .05), even in the subgroup receiving methotrexate doses >3500 mg/m2 . Grade 3 or higher toxicity occurred in 33.3% of the concomitant levetiracetam group and in 34.1% of nonconcomitant levetiracetam patients. This study, which, to our knowledge, is the first examining levetiracetam effect on only the first dose of HDMTX, supports the larger retrospective study finding no significant effect of levetiracetam on HDMTX clearance time, and suggests that administering concomitant levetiracetam does not affect HDMTX toxicity.

Background: Opioid use is classified as an epidemic by many due to the impact of these medications on society. Federal and state laws for prescribing and dispensing opioids have changed rapidly in a short period of time to hopefully balance proper pain control with their use. Pharmacy directors must be informed of these rapid changes to effectively work as part of any opioid stewardship team. Objective: The objective of this study was to provide foundational leadership guidance to pharmacy directors on current opioid legislation, literature, and best practices to assist in improving opioid use. Methods: A review of the literature from 2003 to the present was conducted along with collating important up to date resources and other publications that provide foundational information to help support a comprehensive management of opioid use. A summary of these data has been collated into an easy to use table and summarized throughout this article. Conclusion: The information provided in this article helps to properly inform pharmacy leaders to the resources available to improve the prescribing, dispensing, and monitoring of opioids and alternatives.

PURPOSE: Aromatase inhibitors (AIs) are associated with musculoskeletal symptoms and risk of developing carpal tunnel syndrome (CTS), which can impair quality of life and prompt treatment discontinuation. The incidence of CTS and clinical utility of diagnostic tests such as 2-point discrimination (2-PD) have not been prospectively examined among women receiving AIs. METHODS: Postmenopausal women with stage 0-III hormone receptor-positive breast cancer who were enrolled in a randomized clinical trial investigating adjuvant AIs (Exemestane and Letrozole Pharmacogenetics, ELPh) underwent prospective evaluation of 2-PD with the Disc-criminator™ (sliding aesthesiometer) and completed a CTS questionnaire at baseline, 3, 6, and 12 months, following initiation of AI. Changes in mean 2-PD were analyzed with multivariable mixed effects modelling. A p value < 0.05 was considered statistically significant. RESULTS: Of 100 women who underwent baseline 2-PD testing, CTS was identified by questionnaire in 11% at baseline prior to AI initiation. Prevalence of CTS at any time in the first year was 26%. A significant increase in worst 2-PD score was observed from baseline to 3 months (3.7 mm to 3.9 mm, respectively, p = 0.03) when adjusted for age, prior chemotherapy, randomized treatment assignment, and diabetes. There were no significant differences in treatment discontinuation due to CTS between the arms. CONCLUSION: For women receiving adjuvant AI, 2-PD scores were significantly worse at 3 months compared to baseline. Studies are required to assess whether change in 2-PD is an adequate objective assessment for CTS with AI therapy. Early diagnosis of CTS may expedite management, improve AI adherence, and enhance breast cancer outcomes.

Droplet interface bilayers (DIBs) mimic the cell membrane and provide a model membrane platform for studying basic biophysical processes. This paper demonstrates a pressure-driven microfluidic system for the rapid and automated generation of alternating DIB networks, each comprised of four aqueous nanoliter droplets. The microfluidic device features five inlets, one for the continuous oil phase and four independent aqueous channels for T-junction droplet generation. Droplet production rates are controlled by adjusting the applied pressure of each inlet; therefore, controlling the pattern of droplets produced in the main channel and further stored in a downstream hydrodynamic trapping array. Each trap is designed to capture and hold in place one row of four droplets, forming three interfacial lipid bilayers per network. The potential for greater combinations of droplets in a network enables an increased complexity necessary for performing parallel multiplexed biological assays. We further examined flow behavior in response to changes in resistance of the microfluidic device when using a pressure driven source. This microfluidic system provides a high-throughput method for generating DIB networks of complex droplet patterning.

Prodrugs are designed to improve pharmaceutical properties of potent compounds and represent a central approach in drug development. The success of the prodrug strategy relies on incorporation of a reversible linkage facilitating controlled release of the parent drug. While prodrug approaches enhance pharmacokinetic properties over their parent drug, they still face challenges in absorption, distribution, metabolism, elimination, and toxicity (ADMET). Conjugating a drug to a carrier molecule such as a polymer can create an amphiphile that self-assembles into nanoparticles. These nanoparticles display prolonged blood circulation and passive targeting ability. Furthermore, the drug release can be tailored using a variety of linkers between the parent drug and the carrier molecule. In this review, we introduce the concept of self-assembling prodrugs and summarize different approaches for controlling the drug release with a focus on the linker technology. We also summarize recent clinical trials, discuss the emerging challenges, and provide our perspective on the utility and future potential of this technology.

Background The study aim was to systematically review literature evaluating surgeon volume-outcome relationships for thyroid and parathyroid operations in order to inform surgical quality improvement initiatives. Current literature suggests surgeons who perform a high volume of thyroid and/or parathyroid operations have better outcomes than low volume surgeons, though specific volume definition are not standardized. Methods Eligible studies were selected through a literature search focused on the effect of surgeon volume on thyroid and parathyroid surgery patient outcomes. The literature search was conducted in accordance with the PRISMA guidelines. Publication dates extended from January 1998 to February 2021, and were limited to articles published in English. Results A total of 33 studies were included: 25 studies evaluating thyroid surgery outcomes, 4 studies evaluating parathyroid surgery outcomes, and 4 studies evaluating both thyroid and parathyroid (mixed) surgery outcomes. Higher volume thyroid and parathyroid surgeons were found to be associated with fewer surgical and medical complications, shorter length of hospital stay, and reduced total cost when compared to lower volume surgeons. This volume-outcome relationship was also found to specifically affect the complication and recurrence rates for thyroid cancer patients undergoing surgery, especially for individuals with advanced stage disease. Conclusion The heterogeneity in cut-offs used for characterizing surgeons as high versus low volume, and also in subsequent patient outcome measures, limited direct study comparisons. The trend of improved patient outcomes with higher surgeon volume for both thyroid and parathyroid surgeries was consistently present in all studies reviewed.

Currently, there are no cheap and compact sources in the mid-infrared range that can be modulated at high frequencies. Incandescent sources such as hot membranes and globars are widely used for mid-infrared spectroscopic applications, but for detection or communication applications where fast temperature modulation are desirable, thermal inertia quickly becomes a limiting factor. Besides, such incandescent sources are typically unpolarized, isotropic, broadband and have a low efficiency. However, these properties are not imposed by fundamental limitations stemming from physics laws, except for the low brightness dictated by Bose-Einstein distribution. Here, we introduce a metasurface that combines nanoscale heaters to ensure fast thermal response and nanophotonic resonances to provide large spectrally selective and polarized emissivity. We report a peak emissivity of 0.8 and an operation up to 20 MHz, six orders of magnitude faster than commercially available hot membranes.

Many small-molecule drugs exhibit poor aqueous solubility, and various approaches have been developed to improve their solubility and delivery. Chemical conjugation of an insoluble drug to a hydrophilic polymer can promote the self-assembly into nanoparticles (NPs) to increase the apparent solubility and improve the pharmacokinetics of the drug. However, majority of the reports in the field disclose only one composition of the conjugate, while accumulating evidence suggests that structure-activity relationship (SAR) studies must be conducted to identify an optimal construct. In this study, we employed a click chemistry platform to robustly conjugate short-chain methoxypolyethylene glycol (mPEG) of three different molecular weights to a small molecule anti-inflammatory drug, gambogic acid (GA), and studied the SAR. NPs formed with mPEG550 and mPEG5000, referred to as NP-550 and NP-5000, respectively, had larger mean diameters (130.0 ± 16.9 nm and 143.0 ± 0.1 nm, respectively) and higher critical micellar concentrations (CMCs, 9.5 μg mL-1 and 10.5 μg mL-1, respectively) compared to NPs formed with mPEG2000 (NP-2000, mean diameter = 97.8 ± 5.0 nm and CMC = 6.6 μg mL-1). NP-2000 and NP-5000 did not cause significant hemolytic toxicity, whereas NP-550 and free GA induced 90% and 60% hemolysis, respectively. NP-2000 was selected for further studies due to its improved safety, small size and low CMC. In cultured inflammatory macrophages, NP-2000 exhibited activity comparable to free GA in suppressing tumor necrosis factor-α. In mice, NP-2000 showed 185-fold improved drug exposure compared to free GA after intraperitoneal delivery. Treatment with free GA showed little anti-inflammatory activity compared to vehicle control in a murine model of rheumatoid arthritis. In contrast, NP-2000 significantly reduced the paw inflammation by 27% from day 15 to day 29. NP-2000 showed no visible signs of toxicity in mice, while free GA elicited significant irritation at the injection site. Our work emphasizes the importance of performing SAR studies for developing an optimal drug-polymer conjugate for self-assembly into NPs. We also demonstrate a unique application of click chemistry to robustly synthesize a small library of conjugates for the SAR study.

The Canadian tax program for Scientific Research and Experimental Development (SR&ED) is a crucial component of Canadian economic policy as it encourages domestic companies to engage in risk-taking initiatives through tax incentives such as credits. While the SR&ED program has evolved over the decades, the SR&ED Five Questions have established the principal criteria that determine the eligibility of an SR&ED claim. The key take-away points of this paper are that the Canada Revenue Agency is progressively becoming more particular and stringent when reviewing SR&ED claims and in light of this trend, documentation is becoming ever important in the substantiation of SR&ED claims. Although not required with submission, documentation provides taxpayers with evidence to support their claims in the case of a CRA or court challenge. In the event of an audit, a taxpayer must prove that its SR&ED activities are eligible and meets the “Five Question Test.” As this paper argues, recent case law has shown the importance of clear and relevant supporting evidence, especially documentation, in substantiating that an SR&ED project meets the Five Questions criteria. Key words: Tax, taxation, research and development, accounting, incentive, tax credit, canada, scientific research and experimental development.

This meta-analysis aimed to evaluate the body of evidence investigating the post-operative use of non-opioid analgesic drugs and techniques in endocrine neck surgeries. Adequate pain control is crucial for successful recovery after thyroid and parathyroid surgery. Effective postoperative pain control can shorten hospital stay, improve postoperative outcomes, decrease morbidity and improve the overall patient experience. Traditionally, opioids have been the mainstay of postoperative analgesia after thyroid and parathyroid surgeries. However, the use of opioids has been linked to an increased incidence of postoperative complications.A comprehensive systematic literature review via Medline, Embase, Web of Science and Cochrane Central Register for Controlled Trials from inception until December 26th, 2020 was conducted, followed by meta-analysis. Abstract and full-text screening, data extraction and quality assessment were independently conducted by 2 investigators. Odds ratios (OR), mean differences (MD) and 95% confidence intervals were calculated using RevMan 5.3.Sixty-five randomized control trials were identified from 486 unique publications. Pooled MD and 95% confidence interval for pain scores were higher for the control group at 24 h postoperatively both at rest (-0.65 [-0.92, -0.37]) and with swallowing (-0.77 [-1.37, -0.16]). These differences were statistically significant. The pooled MD and confidence interval for postoperative analgesic requirements was lower in the intervention group (-1.38 [-1.86, -0.90]). The incidence of PONV had a pooled OR of 0.67 [0.48, 0.94].Non-opioid analgesia was superior to the control group for pain control in patients undergoing thyroid and parathyroid operations with no significant difference in complications.

Purpose Results of a study comparing readmission rates and medication adherence measures before and after implementation of a pharmacy-led transitions-of-care (TOC) program are reported. Methods A quasi-experimental case–control study was conducted to assess the impact of a TOC program including medication history-taking and reconciliation services, inpatient and discharge education, and 72-hour and 30-day postdischarge phone follow-up. Hospital and emergency room (ER) readmission rates were compared in cohorts of oncology patients admitted to a large teaching hospital during specified periods before TOC program implementation (the standard-of-care [SOC] group) or after program implementation (the TOC group). The primary outcome was unplanned hospital or ER readmission within 30 days after initial discharge. The secondary endpoint was first-fill medication adherence. Benefits associated with specific TOC interventions were assessed in subgroup analyses. Results After propensity score matching, both study groups consisted of 323 patients. The SOC group had 76 patients (23.5%) and the TOC group had 74 patients (22.9%) who were readmitted to the hospital or ER within 30 days, with a significant reduction in hospital readmissions in 1 subgroup of TOC patients versus SOC controls (absolute difference, −7.6%; p = 0.0159). Conclusion While there were no significant overall differences in readmission rates between the TOC and SOC groups, hospital readmissions were reduced in the subgroup of TOC patients who received both medication history-taking and reconciliation services and phone follow-up as TOC interventions.

This case report follows a right-handed 26-year-old female with a past medical history of schizoaffective disorder, patellofemoral syndrome, De Quervain's tendonitis, and remote foot surgery with acute onset debilitating foot pain from initial presentation at an urgent care facility to her eventual return to work. Special attention is drawn to physical exam findings, natural history, differential diagnosis, clinical pearls, and details on the legal responsibility of physicians. This case study hopes to provide a framework for how physicians and other providers can help patients as they navigate the harsh realities of the healthcare system and provide some key clinical pearls to ensure that the patient is kept front and center in the minds of those providing the necessary healthcare for the patient’s providing the necessary healthcare for the patient’s psychiatric, social, and physical needs. Keywords: Orthopaedics, Bruised Bone, Patient-Centered Care, Diagnostic Work Up, RICE

A wide range of applications ranging from spectroscopy to communication use the mid wavelength infrared (MWIR) spectral range. Fast amplitude modulation is useful for applications such as communications or sensing but out of reach of incandescent emitters. Downsizing the emitter allows overcoming thermal inertia and enabling fast temperature modulation of nanoscale incandescent emitters in contact with a cold substrate. However, while heat conduction to the substrate is required for fast cooling, it is detrimental for the efficiency of the source. Here, we introduce a theoretical model and analyse the influence of the source parameters on the trade-off between fast modulation and efficiency of incandescent sources. We also compare harmonic and pulse modulation.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN), which is characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. PV is distinguished clinically from the other MPNs by the presence of an elevated red blood cell mass, and are commonly noted to have persistent leukocytosis and thrombocytosis. Pruritus, hypertension, vasomotor symptoms like erythromelalgia, thrombosis and bleeding events are well known clinical features of PV, however there is insufficient data on PV and associated cardiac arrhythmias and its repercussions. Through this study we aim to determine baseline characteristics of PV patients with and without arrhythmias and its impact on morbidity, mortality and overall hospital length of stay. We identified all adult hospitalized patients with PV, during the time frame of January 2016 to December 2018, and divided them into groups with and without cardiac arrhythmias using ICD-10-CM Codes from National Inpatient sample Database. We compared patient's baseline characteristics, associated comorbidities, mortality, length of stay and hospitalization costs among PV patients with and without documented arrhythmias. Propensity-score matching for age, sex, income, and co-morbidities were performed among both groups. SAS 9.4 software was used for statistical analysis. We analyzed a total of 61265 patients. Out of this cohort, 20165 (32.9%) patients were found to have cardiac arrhythmias. The group with cardiac arrhythmias were noted to have a higher mean age (75.6±11.6 vs 68.2±14.4 yrs), were predominantly males (57.4 vs 42.6%), and had higher prevalence of associated comorbidities such as congestive heart failure (16.7 vs 8.3%), coronary artery disease (40.1 vs 23.9%), peripheral vascular disease (11.8 vs 9.9%), chronic obstructive lung disease (25.7 vs 23.9%), renal failure (15.5 vs 10.9%), and coagulopathy (7.2 vs 6.2%). In terms of propensity matched outcomes, the group with PV and associated arrhythmias had higher inpatient mortality (5.8 vs 3.2%), longer length of stay (6.4±7.7 vs 5.2±5.3 days) and higher total hospitalization costs (18744±28815 vs 13870±16527 $). Amongst arrhythmias, atrial fibrillation was noted to be the most common arrhythmia (77.6%), followed by atrial flutter (8.2%), ventricular tachycardia (6.6%) and supraventricular tachycardia (6.4%).(p Our study suggests that presence of arrhythmias in patients with PV significantly increases the hospital mortality, total cost and length of stay. Both PV and Arrhythmias are independent risk factors for thrombosis which increases morbidity and mortality outcomes in the patients. We identified a high incidence of atrial arrhythmias among patients with PV. The patients were older, cumulating more cardiovascular risk factors inducing more thrombotic events mainly in arteries, and have a higher incidence of death. PV presents the physician with a significant therapeutic challenge, where the physician has to carefully reflect and act on treating the strong thrombophilic state of PV and arrhythmias with careful caution to prevent bleeding catastrophes. With mounting epidemiological evidence of association and fatal outcomes, our study also shines light on a significant knowledge gap in the field of MPN such as PV and concurrent cardiac arrhythmias and warrants further studies to better delineate pathogenesis and early diagnostic and treatment strategies specifically curated for PV associated arrhythmias. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Polycythemia Vera (PV) is a rare chronic myeloproliferative disorder (MPN), a hematopoietic stem cell-derived malignancy that is characterized by clonal proliferation of myeloid cells with variable degrees of morphologic maturity. PV is distinguished from other MPNs by the presence of an elevated red blood cell mass (ie, erythrocytosis), and is associated with an increased risk for thromboembolic events, leukemic transformation, and/or myelofibrosis. This translates to sludging of blood flow due to hyperviscosity. Patients with PV have increased risk of both arterial and venous thrombosis as well as hemorrhage. Acute coronary syndrome and cardiac thrombotic events are well known complications of PV, however there is insufficient data on PV associated with heart failure (HF) and its repercussions. Through this study we aim to determine baseline characteristics of PV patients with and without HF and its impact on morbidity, mortality and overall hospital length of stay. We identified all hospitalized adult patients with PV from the National Inpatient Sample Database between January 2016 to December 2018 using ICD-10-CM codes, and divided them into groups with and without heart failure. We compared patient's baseline characteristics, associated comorbidities, mortality, length of stay and hospitalization costs among PV patients with and without HF. Propensity-score 1:1 matching for age, sex, race, and co-morbidities was performed among both groups. SAS 9.4 software was used for statistical analysis. Out of 61265 patients hospitalized with PV, 16900(27.6%) patients were found to have HF. The patients in HF group were noted to have higher mean age (74.7±12.3 vs 69±14.3 years), and higher prevalence of comorbidities such as diabetes mellitus (27.5 vs 20.4%), coronary artery disease (47.2 vs 22.4%), peripheral vascular disease (12.1 vs 9.9%), chronic pulmonary obstructive disease (33.9 vs 20.6%), Renal failure (20.2 vs 9.4%) and obesity (13.6 vs 10.5%). In terms of propensity matched outcomes, the group with PV and coexisting HF had higher inpatient mortality (5.9 vs 3.6%), higher total length of stay (6.5 ± 7.3 vs 5.2 ± 5.3 days), and higher total hospitalization cost (18081 ± 27506 vs 14529 ± 18412 $) (p Our study noted that almost 27.6% of hospitalized PV patients had concurrent HF. We observed that presence of HF in patients with PV significantly increased mortality, hospitalization costs and total length of stay. Despite major advances in Heart failure (HF) treatment strategies, morbidity and mortality remains high. With regard to the etiology, there are different causes of HF, and their recognition can be crucial for treatment optimization. With mounting epidemiological evidence of association and fatal outcomes, our study also shines light on a significant knowledge gap in the field of MPN such as PV and concurrent HF, and warrants further studies to better delineate pathogenesis and early diagnostic and treatment strategies specifically curated for PV associated HF. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background Lipoprotein(a) [Lp(a)] is an important cardiovascular risk factor, but clinical immunoassays are flawed. Apolipoprotein(a) [apo(a)], the characteristic protein of Lp(a), contains a variable number of kringle repeats (size isoforms) that make accurate measurement of Lp(a) difficult. We developed a sandwich enzyme immunoassay that uses a murine monoclonal anti-apo(a) antibody for capture and a polyclonal anti-apolipoprotein B (apo B) for detection. Because Lp(a) contains one molecule each of apo(a) and apo B, the assay measures the number of Lp(a) particles [Lp(a)-P] in the circulation without bias due to apo(a) size isoforms. Methods After developing and choosing the best anti-apo(a) clone for Lp(a) capture, we identified suitable reagents and ELISA conditions, and validated assay performance (precision, linearity, limit of detection, interferences, and apo(a) size isoform bias). Results The Lp(a)-P assay was precise with within-run precision of 5.5% to 7.2% and total imprecision of 6.9% to 12.1%. The assay had a limit of detection of 13 nmol/l and was linear from 2 to 499 nmol/l. There was no interference from plasminogen or apolipoprotein B up to 80 and 200 mg/dl, respectively, and bias plot showed no bias related to apo(a) size (kringle 4 type 2 repeats). Conclusions Lp(a)-P assay is sensitive, precise and linear over a wide analytical range and is a suitable alternative for laboratories concerned about inaccuracy due to apo(a) size polymorphism and the poor performance of immunoturbidimetric assays.

A primary focus of the rapidly growing field of plant synthetic biology is to develop technologies to precisely regulate gene expression and engineer complex genetic circuits into plant chassis. At present, there are few orthogonal tools available for effectively controlling gene expression in plants, with most researchers instead using a limited set of viral elements or truncated native promoters. A powerful repressible-and engineerable-binary system that has been repurposed in a variety of eukaryotic systems is the Q-system from Neurospora crassa. Here, we demonstrate the functionality of the Q-system in plants through transient expression in soybean (Glycine max) protoplasts and agroinfiltration in Nicotiana benthamiana leaves. Further, using functional variants of the QF transcriptional activator, it was possible to modulate the expression of reporter genes and to fully suppress the system through expression of the QS repressor. As a potential application for plant-based biosensors (phytosensors), we demonstrated the ability of the Q-system to amplify the signal from a weak promoter, enabling remote detection of a fluorescent reporter that was previously undetectable. In addition, we demonstrated that it was possible to coordinate the expression of multiple genes through the expression of a single QF activator. Based on the results from this study, the Q-system represents a powerful orthogonal tool for precise control of gene expression in plants, with envisioned applications in metabolic engineering, phytosensors, and biotic and abiotic stress tolerance.

This work draws inspiration from totipotent cellular systems to design smart materials whose compositions and properties can be learned or evolved. Totipotency refers to the inherent genetic potential of a single cell to adapt and produce all types of differentiated cells within an organism. To study this principal and apply it synthetically, tissue-like compartmentalized assemblies are constructed via lipid membrane-separated aqueous droplets in a hydrophobic medium through the droplet interface bilayer (DIB) method. Within our droplets, we explore synthetic totipotency via cell-free reactions including actin polymerization and cell free protein synthesis (CFPS). The transcription and translation of our CFPS reactions are controlled by stimuli-responsive riboswitches (RS). Via this scheme, adaptable material properties and functions are achieved in vitro via protein production from cell-free machinery administered through RS governance. Here, we present thermally or chemically-triggered riboswitches for orthogonal production of representative fluorescent protein products, as well functional proteins. To characterize the material properties of target proteins, we study the formation of polymerized actin shells to stabilize organically-encased droplets and span DIBs. We present a modified protocol for chemically-triggered actin polymerization as well as a thermally triggered actin RS. We characterize theophylline (TP)-triggered production of alpha hemolysin (α-HL) through CFPS and synthesized an organic-soluble trigger that can be sensed from the oil phase by a RS in an aqueous bioreactor droplet. We also demonstrate increased droplet conductivity when CFPS α-HL products are incorporated in DIBs. This interdisciplinary work involves cell culture, gene expression, organic synthesis, vesicle formation, protein quantification, tensiometry, droplet aspiration, microplate fluorescence/absorption experiments, fluorescent microscopy, and electrophysiology. This project is an essential design analysis for creating smart, soft materials using synthetic biology and provides motivation for artificial tissues capable of adapting in response to external stimuli.

With scientific evidence regarding the contribution of carbon emissions to global warming mounting, pressure is building for corrective policy actions. The potential for such policies poses a risk for invested capital. We describe how bond investors using traditional portfolio construction techniques can hedge portfolios against this climate risk without introducing unintended exposures that could sacrifice the portfolio’s benchmark-tracking properties. We hypothesize how a pickup in low-carbon investing may send out a pricing signal and preempt the connoted price correction. In that event, the transition toward a world economy with a sustainable level of carbon pollution would be accelerated, which would be beneficial for both the low-carbon investor and the environment.

PURPOSE: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are common adverse events of AIs often leading to drug discontinuation. We initiated a prospective clinical trial to evaluate whether bisphosphonates are associated with reduced incidence of AIMSS. METHODS: In the single-arm trial, the Zoledronic Acid Prophylaxis (ZAP) trial, we compared the incidence of AIMSS against historical controls from the Exemestane and Letrozole Pharmacogenomics (ELPh) trial. Eligible women were postmenopausal with stage 0-III breast cancer planning to receive adjuvant AIs. AIMSS was assessed using the Health Assessment Questionnaire and Visual Analog Scale over 12 months in both trials. Participants in the ZAP trial received zoledronic acid prior to initiating letrozole and after 6 months; ELPh participants included in the analysis were taking letrozole but not bisphosphonates. We analyzed patient-reported outcomes (PROs) and bone density in the ZAP trial using mixed-effects linear regression models and paired t tests, respectively. RESULTS: From 2011 to 2013, 59 postmenopausal women enrolled in ZAP trial. All 59 (100%) women received baseline and 52 (88%) received 6-month zoledronic acid, and had similar characteristics to historical controls from the ELPh trial (n = 206). Cumulatively during the first year of AI, 37 and 67% of ZAP and ELPh participants reported AIMSS (p < 0.001), respectively. Within the ZAP trial, we did not observe significant changes in other PROs; however, we report improvements in bone mineral density. CONCLUSIONS: Compared to historical controls, zoledronic acid administered concomitantly with adjuvant AIs was associated with a reduced incidence of AIMSS. A randomized controlled trial is required to confirm these findings.

© 2018, © The Author(s) 2018. This study examined cross-cultural differences in parental interpretations of childhood separation anxiety disorder (SAD) symptoms and their subsequent likelihood to seek help or advice. It also assessed level of acculturation to Western society as a potential predictor of Asian parents’ judgments of perceived pathology and likelihood to seek help. A total of 108 Caucasian and Asian parents were presented with a vignette of a child displaying behaviors indicative of SAD and asked to rate their level of perceived pathology and likelihood to seek help. Results showed that Caucasian and Asian parents gave similar ratings of perceived pathology. However, Caucasian parents reported a greater likelihood to seek help or advice for SAD symptoms than Asian parents. Level of acculturation to Western society was not a statistically significant predictor of Asian parents’ perceptions and likelihood to seek help, above and beyond the variance explained by demographic factors and level of shame associated with help seeking. Although conclusions are discussed in light of methodological limitations, these preliminary findings highlight the importance of considering cultural factors when investigating children’s access to mental health services, especially when the presenting issue is SAD.

The droplet interface bilayer (DIB) method offers simple control over initial leaflet compositions in model membranes, enabling an experimental path to filling gaps in our knowledge about the interplay between compositional lipid asymmetry, membrane properties, and the behaviors of membrane-active species. Yet, the stability of lipid leaflet asymmetry in DIBs has received very little attention, particularly in the presence of peptides and ion channels that are often studied in DIBs. Herein, we demonstrate for the first time parallel, capacitance-based measurements of intramembrane potential with arrays of asymmetric DIBs assembled in a microfluidic device to characterize the stability of leaflet asymmetry over many hours in the presence and absence of membrane-active peptides. DIBs assembled from opposing monolayers of the ester (DPhPC) and ether (DOPhPC) forms of diphytanoyl-phosphatidylcholine yielded asymmetric bilayers with leaflet compositions that were stable for at least 18 h as indicated by a stable |137 mV| intramembrane potential. In contrast, the addition of surface-bound alamethicin peptides caused a gradual, concentration-dependent decrease in the magnitude of the dipole potential difference. Intermittent current-voltage measurements revealed that alamethicin in asymmetric DIBs also shifts the threshold voltage required to drive peptide insertion and ion channel formation. These outcomes take place over the course of 1 to 5 h after membrane formation, and suggest that alamethicin peptides promote lipid flip-flop, even in the un-inserted, surface-bound state, by disordering lipids in the monolayer to which they bind. Moreover, this methodology establishes the use of parallel electrophysiology for efficiently studying membrane asymmetry in arrays of DIBs.

In this study, we utilize a novel microfluidic device to perform simultaneous electrical interrogation of an array of droplet interface bilayers (DIB) that feature asymmetric phospholipid leaflet compositions. While asymmetry is vital to many cellular functions, it is has received very little attention in membrane-based engineered material systems for sensing, energy conversion, or actuation. This gap is due to challenges in constructing and interrogating networks of asymmetric membranes, limiting our understanding of how lipid asymmetry affects membrane active peptides, and vice versa. Our system overcomes these difficulties by enabling asymmetric membrane formation between many pairs of lipid-coated droplets in oil. We demonstrate its use in probing the interactions between alamethicin, a membrane-active peptide that forms voltage-induced ion channels, and asymmetric DPhPC:DOPhPC membranes, a choice that creates an intrinsic intramembrane potential of |137 mV| due to differences in their respective dipole potentials. Our experiments show that adding alamethicin peptides to one side of the membrane causes this inherent membrane potential to decrease over time, and it alters the value of external voltage that must be applied to drive alamethicin insertion for ion channel formation. These effects take place over the course of 1 to 5 hours after membrane formation, and both results are consistent with translocation and mixing of lipids across the leaflets of the membrane.

Nursing work increasingly demands forms of expertise that complement specialist knowledge. In child and family nursing, this need arises when nurses work in partnership with parents of young children at risk. Partnership means working with parents in respectful, negotiated and empowering ways. Existing partnership literature emphasises communicative and relational skills, but this paper focuses on nurses' capacities to facilitate parents' learning. Referring to data from home visiting, day-stay and specialist toddler clinic services in Sydney, a pedagogical framework is presented. Analysis shows how nurses notice aspects of children, parents and parent-child interactions as a catalyst for building on parents' strengths, enhancing guided chance or challenging unhelpful constructs. Prior research shows the latter can be a sticking point in partnership, but this paper reveals diverse ways in which challenges are folded into learning process that position parents as agents of positive change. Noticing is dependent on embodied and communicative expertise, conceptualised in terms of sensory and reported channels. The framework offers a new view of partnership as mind-expanding for the parent and specifies the nurse's role in facilitating this process.

The biologic processes underlying epileptogenesis following a brain insult are not fully understood, but several lines of evidence suggest that hyperphosphorylation of tau may be an important factor in these processes. To provide further insight into the causal relationship between tau and epileptogenesis, this study applied amygdala kindling to rTg4510 mice that, concurrent with other pathologies, overexpress phosphorylated tau, tau knockout mice, or their respective wild-type controls. Mice were electrically stimulated twice daily, 5 days per week for 3 weeks. Electroencephalography was recorded to measure the primary afterdischarge duration, and the behavioral progression of kindling-induced seizures was assessed. rTg4510 mice (n = 10) had increased primary afterdischarge durations (p < 0.001), and significantly more rapid progression of kindling (p < 0.001), compared with wild-type mice (n = 10). Tau knockout mice (n = 7), however, did not differ from their wild-type counterparts (n = 8) on any of the seizure outcomes. These results suggest that Tg4510 mice are more vulnerable to epileptogenesis, but that the presence of tau itself is not necessary for kindling epileptogenesis to occur.

Purpose The development and implementation of a pharmacy-driven, postdischarge follow-up telephone call program to assess medication adherence, provide education, and address medication-related concerns are discussed. Summary Many readmissions are avoidable through effective discharge planning and patient follow-up after hospitalization. However, there is limited information on how to effectuate this process. To address this barrier, a team consisting of a clinical pharmacy specialist, a clinical pharmacy manager, a postgraduate year 1 pharmacy resident, and an education specialist at The University of Texas MD Anderson Cancer Center collaborated to create a postdischarge telephone call program within a transitions-of-care (TOC) pilot program. Various education and training materials were created to ensure trainees were competent. As of February 2016, 23 outpatient pharmacists and students have completed training, earning a median pretest and posttest score of 6 and 9, respectively, out of 10. There have been 206 calls completed; 150 patients (73%) were successfully reached, and 20 patients (9%) declined the telephone call. Medication adherence assessed during the telephone follow-up identified that 134 patients (89%) received their new medications within 72 hours, and 87 patients (58%) were recognized as having one or more discrepancies. Conclusion Developing a TOC program similar to this pilot program requires several resources including time, collaboration, and support from the management team. Pharmacy is well positioned to complete an accurate medication review and conduct postdischarge telephone calls to address medication-related issues. By providing these services, patients will receive continuity of care and positively impact emergency room visitation rates and hospital readmission rates.

Despite the considerable potential for e-learning to improve learning outcomes, particularly for female students and students who need to rely on distance learning, feedback from current users of e-learning systems in the Kingdom of Saudi Arabia (KSA) suggests a relatively low level of satisfaction. This study adopts a mixed-methods approach in investigating the underlying reasons for this situation. Results indicate that students are not unhappy with the information technology infrastructure or with other technical aspects. However, many students report a low level of interaction between them and their fellow students. When interactions do occur, students indicate overwhelmingly that they find such interactions useful. Together, these findings suggest that greater student interaction, which could be fostered through the use of collaborative learning, is likely to be both popular with students and beneficial to their learning outcomes.