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It is suggested that in addition to seismicity deep fluid injection may cause surface uplift and subsidence in oil and gas-producing regions. This study uses the Raton Basin as an example to investigate the hydromechanical processes of surface uplift and subsidence during wastewater injection. The Raton Basin, in southern central Colorado and northern central New Mexico, has experienced wastewater injection related to coalbed methane and gas production starting in 1994. In this study, we estimate the extent and magnitude of total vertical deformation in the Raton Basin from 1994 to 2020 and incremental deformation between the years 2017 to 2020. Results indicate a modeled uplift as much as 15 cm occurring between 1994 and 2020. Between 2017 and 2020, up to 3 cm of uplift occurred, largely near the northwestern injection wells. Most modeled uplift between 1994 and 2020 occurred near the southern wells, where the greatest cumulative volume of wastewater was injected. However, modeled subsidence occurred around the southern and eastern wells between 2017 and 2020, after the rate of injection decreased. Modeling indicates that while the magnitude of modeled uplift corresponds to cumulative injection volume and maximum rate in the long-term, short-term incremental deformation (uplift or subsidence) is controlled by changes in the rate of injection. The number of yearly earthquake events follows periods of rapid modeled uplifting throughout the Basin, suggesting that measurable surface deformation may be caused by the same injection-induced pore pressure perturbations that initiate seismicity., (© 2024 The Authors. Groundwater published by Wiley Periodicals LLC on behalf of National Ground Water Association.)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC ( Pdx1-Cre , LSL-Kras G12D/+ , LSL-Trp53 R172H/+ ) and poorly metastatic KP fl C ( Pdx1-Cre , LSL-Kras G12D/+ , Trp53 fl/+ ) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KP fl C, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget.

Although initially successful, treatments with chemotherapy often fail because of the recurrence of chemoresistant metastases. Since these tumors develop after treatment, resistance is generally thought to occur in response to chemotherapy. However, alternative mechanisms of intrinsic chemoresistance in the chemotherapy-naïve setting may exist but remain poorly understood. Here, we study drug-naïve murine breast cancer brain metastases (BCBMs) to identify how cancer cells growing in a secondary site can acquire intrinsic chemoresistance without cytotoxic agent exposure. We demonstrate that drug-naïve murine breast cancer cells that form cancer lesions in the brain undergo vascular mimicry and concomitantly express the adenosine 5'-triphosphate-binding cassette transporter breast cancer resistance protein (BCRP), a common marker of brain endothelial cells. We reveal that expression of BCRP by the BCBM tumor cells protects them against doxorubicin and topotecan. We conclude that BCRP overexpression can cause intrinsic chemoresistance in cancer cells growing in metastatic sites without prior chemotherapy exposure.

The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-5505, a first-in-class highly selective and potent pan-lysyl oxidase inhibitor. We demonstrate in vitro and in vivo that pan-lysyl oxidase inhibition decreases chemotherapy-induced pancreatic tumor desmoplasia and stiffness, reduces cancer cell invasion and metastasis, improves tumor perfusion and enhances the efficacy of chemotherapy in the autochthonous genetically engineered KPC model, while also demonstrating antifibrotic effects in human patient-derived xenograft models of pancreatic cancer. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues. Our findings present the rationale for progression of a pan-lysyl oxidase inhibitor aimed at eliciting a reduction in stromal matrix to potentiate chemotherapy in pancreatic ductal adenocarcinoma., (© 2023. The Author(s).)

The extracellular matrix (ECM) is a non-cellular network of macromolecules, which provides cells and tissues with structural support and biomechanical feedback to regulate cellular function, tissue tension, and homeostasis. Even subtle changes to ECM abundance, architecture, and organization can affect downstream biological pathways, thereby influencing normal cell and tissue function and also driving disease conditions. For example, in cancer, the ECM is well known to provide both biophysical and biochemical cues that influence cancer initiation, progression, and metastasis, highlighting the need to better understand cell-ECM interactions in cancer and other ECM-enriched diseases. Initial cell-derived matrix (CDM) models were used as an in vitro system to mimic and assess the physiologically relevant three-dimensional (3D) cell-ECM interactions. Here, we describe an expansion to these initial CDM models generated by fibroblasts to assess the effect of genetic or pharmacological intervention on fibroblast-mediated matrix production and organization. Additionally, we highlight current methodologies to quantify changes in the ultrastructure and isotropy of the resulting ECM and also provide protocols for assessing cancer cell interaction with CDMs. Understanding the nature and influence of these complex and heterogeneous processes can offer insights into the biomechanical and biochemical mechanisms, which drive cancer development and metastasis, and how we can target them to improve cancer outcomes. This protocol was validated in: Sci Adv (2021), DOI: 10.1126/sciadv.abh0363., Competing Interests: Competing interests P.T. receives reagents from Kadmon Inc., InxMed (consultant), Redx Pharma, Équilibre Biopharmaceuticals, and Amplia Therapeutics. Under a licensing agreement between Amplia Therapeutics and Garvan Institute of Medical Research, K.J.M., D.H., and P.T. (consultant) are entitled to milestone payments., (Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.)

Introduction: The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world., Methods: A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival., Results: Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1-7.4), and median overall survival of 11.1 months (95% CI, 9.5-12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8-6.5), and median overall survival of 19.3 months (95% CI, 12.6-26.0)., Conclusions: The patient's progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

Purpose: Our objective was to determine what vial sharing techniques and other strategies were being used globally to reduce wastage from partially used single-use drug vials, what barriers are preventing these strategies being employed, and what savings are being achieved., Methods: A survey, comprising 19 questions, was distributed to the membership of the International Society of Oncology Pharmacy Practitioners and British Oncology Pharmacy Association. Questions asked included how parenteral cancer drugs are obtained and prepared, what vial sharing strategies are used, what means are employed to extend stability, how prepared products are reused and what cost savings are achieved., Results: In all, 74 responses were received from 20 countries, most from the United Kingdom. Some manufacturing is done by 60.8% of institution, with 41.9% making all products. Vial sharing strategies, for frequently used drugs, were employed in 53% of cases. Barriers preventing vial sharing being used included government legislation, USP 797 guidelines, and health insurance companies. Extension of stability was possible for 70.2% of centres. Most respondents reported reduction in cytotoxic and biological waste, and alleviation of drug shortages from vial sharing utilisation. Cost savings were achieved in 74% of cases and was significant in one third., Conclusions: The survey has determined that drug vial wastage and expenditure can be reduced, and vial sharing facilitates this. International collaboration plus the assistance of governments and the pharmaceutical industry is vital in achieving this aim. These findings can hopefully guide oncology pharmacy in establishing appropriate strategies to reduce wastage internationally.

Introduction: Palliative care aims to improve the quality of life of patients with a life-limiting or life-threatening illness and is multifaceted involving comprehensive interdisciplinary assessments and interventions. Interdisciplinary palliative care in the setting of untreatable cancer diagnoses is of particular importance due to additional considerations that must be taken as patients are often undergoing palliative chemotherapy and/or radiation therapy. These patients' complexity warrants special considerations and attentiveness to drug-related problems., Case Report: The purpose of this case report is to highlight the importance of both complete and comprehensive medication histories in cancer care and the impact of proton pump inhibitors on pancreatic enzyme insufficiencies secondary to pancreatic cancers. This case involves a drug-related problem involving three medications that are commonly used in pancreatic cancer patients: pancreatic enzyme replacement therapy, a proton pump inhibitor, and a fluoroquinolone antibiotic. The patient presented in this case report is an 80-year-old man diagnosed with unresectable pancreatic cancer with a history of symptomatic gastroesophageal reflux disease managed with a proton pump inhibitor, specifically tablets of the 40 mg strength of pantoprazole magnesium taken orally once daily. During the patient's first of five 28-day cycles of palliative-intent chemotherapy with gemcitabine and nab -paclitaxel, the patient presented to the emergency department due to fever and, although not severely neutropenic, was prescribed amoxicillin/clavulanate and ciprofloxacin due to his advanced age. After reading a patient advisory on a ciprofloxacin patient information sheet that advised avoidance of concomitant administration of ciprofloxacin and magnesium, the patient self-discontinued his pantoprazole as it was a magnesium salt formulation. This discontinuation was followed by two weeks of persistent foul-smelling diarrhea, flatulence, and abdominal pain., Management and Outcome: The patient's healthcare team symptomatically managed the patient with oral and intravenous rehydration unaware of the cause of the symptoms. A trial of pancreatic enzyme replacement therapy was initiated; however, it was unsuccessful in resolving his symptoms. After further investigation and a more in-depth patient interview, it was discovered that the discontinued proton pump inhibitor was likely the cause of the patient's new symptoms and was subsequently re-initiated. Pancreatic enzyme replacement therapy in combination with re-initiation of pantoprazole therapy essentially resolved all symptoms., Discussion: Before his diagnosis of unresectable pancreatic cancer, the patient had been on proton pump inhibitor therapy for nearly a decade. He had significant atrophy of the pancreas and an undoubtedly decreased pancreatic enzyme and bicarbonate production; however, he did not experience foul-smelling diarrhea indicative of pancreatic enzyme insufficiency while he was on his proton pump inhibitor. We believe that with his proton pump inhibitor therapy, he was unknowingly being partially treated for his worsening pancreatic enzyme insufficiency, specifically the component related to his lack of bicarbonate production and secretion. His discontinuation of his proton pump inhibitor led to a decrease in gastric acid, small bowel, and normal intraduodenal pH, which resulted in any remaining pancreatic enzyme reserve to become non-functional, unmasking his pancreatic enzyme insufficiency. An initial empiric trial of pancreatic enzyme replacement therapy failed in the absence of a proton pump inhibitor; however, within days of restarting his proton pump inhibitor along with pancreatic enzyme replacement therapy, his gastrointestinal symptoms completely resolved. This is due to the decrease of gastric and intraduodenal acidity, which better enabled the function of pancreatic enzymes present in pancreatic enzyme replacement therapy.

Senescence is a cellular state in which cells undergo persistent cell cycle arrest in response to nonlethal stress. In the treatment of cancer, senescence induction is a potent method of suppressing tumour cell proliferation. In spite of this, senescent cancer cells and adjacent nontransformed cells of the tumour microenvironment can remain metabolically active, resulting in paradoxical secretion of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP). The SASP plays a critical role in tumorigenesis, affecting numerous processes including invasion, metastasis, epithelial-to-mesenchymal transition (EMT) induction, therapy resistance and immunosuppression. With increasing evidence, it is becoming clear that cell type, tissue of origin and the primary cellular stressor are key determinants in how the SASP will influence tumour development and progression, including whether it will be pro- or antitumorigenic. In this review, we will focus on recent evidence regarding therapy-induced senescence (TIS) from anticancer agents, including chemotherapy, radiation, immunotherapy, and targeted therapies, and how each therapy can trigger the SASP, which in turn influences treatment efficacy. We will also discuss novel pharmacological manipulation of senescent cancer cells and the SASP, which offers an exciting and contemporary approach to cancer therapeutics. With future research, these adjuvant options may help to mitigate many of the negative side effects and protumorigenic roles that are currently associated with TIS in cancer., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic, chemoresistant malignancy and is characterized by a dense, desmoplastic stroma that modulates PDAC progression. Here, we visualized transient manipulation of focal adhesion kinase (FAK), which integrates bidirectional cell-environment signaling, using intravital fluorescence lifetime imaging microscopy of the FAK-based Förster resonance energy transfer biosensor in mouse and patient-derived PDAC models. Parallel real-time quantification of the FUCCI cell cycle reporter guided us to improve PDAC response to standard-of-care chemotherapy at primary and secondary sites. Critically, micropatterned pillar plates and stiffness-tunable matrices were used to pinpoint the contribution of environmental cues to chemosensitization, while fluid flow–induced shear stress assessment, patient-derived matrices, and personalized in vivo models allowed us to deconstruct how FAK inhibition can reduce PDAC spread. Last, stratification of PDAC patient samples via Merlin status revealed a patient subset with poor prognosis that are likely to respond to FAK priming before chemotherapy.

Medication Reconciliation (MedRec) is an essential part of safe medication management and plays a key role in ensuring patient safety. A variety of methods and a number of different healthcare disciplines can be involved in the MedRec process and the timing and location of conducting MedRec can vary. In an effort to streamline the process in ambulatory oncology new patient clinics, a pilot of an alternative approach was undertaken whereby pharmacists with advanced prescribing privileges completed MedRec with patients prior to their clinic visit. Evaluation of the pilot was completed through the collection of various metrics, a pharmacist focus group, healthcare staff and patient surveys. Overall the evaluation indicated that there are multiple factors to consider regarding the timing and method of MedRec completion. The various phases of the pilot demonstrated that flexibility to the process is key and ongoing efforts are required at reducing duplication.

The flanking regions of Guaymas Basin, a young marginal rift basin located in the Gulf of California, are covered with thick sediment layers that are hydrothermally altered due to magmatic intrusions. To explore environmental controls on microbial community structure in this complex environment, we analyzed site- and depth-related patterns of microbial community composition (bacteria, archaea, and fungi) in hydrothermally influenced sediments with different thermal conditions, geochemical regimes, and extent of microbial mats. We compared communities in hot hydrothermal sediments (75-100°C at ~40 cm depth) covered by orange-pigmented Beggiatoaceae mats in the Cathedral Hill area, temperate sediments (25-30°C at ~40 cm depth) covered by yellow sulfur precipitates and filamentous sulfur oxidizers at the Aceto Balsamico location, hot sediments (>115°C at ~40 cm depth) with orange-pigmented mats surrounded by yellow and white mats at the Marker 14 location, and background, non-hydrothermal sediments (3.8°C at ~45 cm depth) overlain with ambient seawater. Whereas bacterial and archaeal communities are clearly structured by site-specific in-situ thermal gradients and geochemical conditions, fungal communities are generally structured by sediment depth. Unexpectedly, chytrid sequence biosignatures are ubiquitous in surficial sediments whereas deeper sediments contain diverse yeasts and filamentous fungi. In correlation analyses across different sites and sediment depths, fungal phylotypes correlate to each other to a much greater degree than Bacteria and Archaea do to each other or to fungi, further substantiating that site-specific in-situ thermal gradients and geochemical conditions that control bacteria and archaea do not extend to fungi., Competing Interests: The authors declared that no competing interest exist.

Many cancer studies now recognize that disease initiation, progression, and response to treatment are strongly influenced by the microenvironmental niche. Widespread desmoplasia, or fibrosis, is fundamental to pancreatic cancer development, growth, metastasis, and treatment resistance. This fibrotic landscape is largely regulated by cancer-associated fibroblasts (CAFs), which deposit and remodel extracellular matrix (ECM) in the tumor microenvironment (TME). This review will explore the prognostic and functional value of the stromal compartment in predicting outcomes and clinical prognosis in pancreatic ductal adenocarcinoma (PDAC). We will also discuss the major dynamic stromal alterations that occur in the pancreatic TME during tumor development and progression, and how the stromal ECM can influence cancer cell phenotype, metabolism, and immune response from a biochemical and biomechanical viewpoint. Lastly, we will provide an outlook on the latest clinical advances in the field of anti-fibrotic co-targeting in combination with chemotherapy or immunotherapy in PDAC, providing insight into the current challenges in treating this highly aggressive, fibrotic malignancy.

Medication errors involving look alike sound alike (LASA) medications have widely been recognized to contribute to patient harm. Oncology biosimilars are considered to be LASA medications and require additional measures for operational safety. The Cancer Care Alberta (CCA) Pharmacy Educators developed an education strategy to ensure operational and patient safety during the implementation phase for oncology biosimilars in Alberta, Canada. This resulted in a smooth adoption of oncology biosimilars. As future oncology biosimilars are introduced, this framework will serve as the foundation to educate and train oncology pharmacy staff.

The Oncology Pharmacy Team (OPT), consisting of specialty-trained pharmacists and/or pharmacy technicians, is an integral component of the multidisciplinary healthcare team (MHT) involved with all aspects of cancer patient care. The OPT fosters quality patient care, safety, and local regulatory compliance. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on five key areas: 1) oncology pharmacy practice as a pharmacy specialty; 2) contributions to patient care; 3) oncology pharmacy practice management; 4) education and training; and 5) contributions to oncology research and quality initiatives to involve the OPT. This position statement advocates that: 1) the OPT be fully incorporated into the MHT to optimize patient care; 2) educational and healthcare institutions develop programs to continually educate OPT members; and 3) regulatory authorities develop certification programs to recognize the unique contributions of the OPT in cancer patient care.

Chemotherapy checking is a complex task and requires a high level of alertness and attention to detail. Learning tools are required to teach the fundamental principles of chemotherapy checking. In conjunction with a graphic design team and with input from Human Factors specialists, an online chemotherapy checking training module was created. A variety of learning methods were incorporated including pre-reading, hands on training, case scenarios, and exam questions. The necessary skills to safely complete chemotherapy checking can be enhanced by the use of this training module.

Cancer-associated fibroblasts (CAFs) are one of the most significant components in the tumour microenvironment (TME), where they can perform several protumourigenic functions. Several studies have recently reported that CAFs are more heterogenous and plastic than was previously thought. As such, there has been a shift in the field to study CAF subpopulations and the emergent functions of these subsets in tumourigenesis. In this review, we explore how different aspects of CAF heterogeneity are defined and how these manifest in multiple cancers, with a focus on pancreatic ductal adenocarcinoma (PDAC). We also discuss therapeutic approaches to selectively target protumourigenic CAF functions, while avoiding normal fibroblasts, providing insight into the future of stromal targeting for the treatment of PDAC and other solid tumours., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The Guaymas Basin spreading center, at 2000 m depth in the Gulf of California, is overlain by a thick sedimentary cover. Across the basin, localized temperature anomalies, with active methane venting and seep fauna exist in response to magma emplacement into sediments. These sites evolve over thousands of years as magma freezes into doleritic sills and the system cools. Although several cool sites resembling cold seeps have been characterized, the hydrothermally active stage of an off-axis site was lacking good examples. Here, we present a multidisciplinary characterization of Ringvent, an ~1 km wide circular mound where hydrothermal activity persists ~28 km northwest of the spreading center. Ringvent provides a new type of intermediate-stage hydrothermal system where off-axis hydrothermal activity has attenuated since its formation, but remains evident in thermal anomalies, hydrothermal biota coexisting with seep fauna, and porewater biogeochemical signatures indicative of hydrothermal circulation. Due to their broad potential distribution, small size and limited life span, such sites are hard to find and characterize, but they provide critical missing links to understand the complex evolution of hydrothermal systems.

InterPro family IPR020489 comprises ~1000 uncharacterized bacterial proteins. Previously we showed that overexpressing the Escherichia coli representative of this family, EcYejG, conferred low-level resistance to aminoglycoside antibiotics. In an attempt to shed light on the biochemical function of EcYejG, we have solved its structure using multinuclear solution NMR spectroscopy. The structure most closely resembles that of domain III from elongation factor G (EF-G). EF-G catalyzes ribosomal translocation and mutations in EF-G have also been associated with aminoglycoside resistance. While we were unable to demonstrate a direct interaction between EcYejG and the ribosome, the protein might play a role in translation., (© 2019 Wiley Periodicals, Inc.)

Increasingly stringent pharmacy standards for preparation of sterile products necessitated a review of the feasibility of continuing to maintain chemotherapy sterile production facilities across the provincial cancer programme. The concept of centrally produced chemotherapy that could be shipped to various locations as a remote service delivery model was explored. Key planning principles were established and detailed processes were developed to test this change in service delivery at one small cancer centre. Following the successful implementation and evaluation of the remote service delivery model at one centre, the programme was rolled out to an additional four centres.

Background: First-line adjuvant chemotherapy options for early-stage colorectal cancer (CRC) include CapeOx (capecitabine, intravenous oxaliplatin) and FOLFOX (intravenous 5-fluorouracil, leucovorin, oxaliplatin). Capecitabine is an oral prodrug analog of 5-fluorouracil, and recent studies have suggested that proton pump inhibitors (PPIs) may detrimentally affect capecitabine efficacy. Conversely, some literature suggests that PPIs may negatively affect CRC itself. To gain insight into the nature of PPIs' effect on capecitabine and CRC, we investigated their effects on effectiveness of CapeOx versus FOLFOX chemotherapy., Patients and Methods: We conducted a retrospective chart review of 389 patients with stage II-III CRC who received adjuvant CapeOx or FOLFOX from 2004 to 2013. Information regarding PPI receipt, chemotherapy, and patient outcomes from medical records was analyzed., Results: Three-year recurrence-free survival was significantly lower in CapeOx-treated PPI recipients than non-PPI recipients (69.5 vs. 82.6%; P = .029). Unadjusted analysis showed that CapeOx-treated PPI recipients were twice as likely to experience cancer recurrence or death as CapeOx-treated non-PPI recipients (hazard ratio = 2.03; 95% confidence interval, 1.06-3.88; P = .033). FOLFOX-treated PPI recipients had a non-statistically significant difference in 3-year recurrence-free survival versus non-PPI recipients (82.9 vs. 61.7%; P = .066) and a non-statistically significant difference in recurrence/death (hazard ratio = 0.51; 95% confidence interval, 0.25-1.06; P = .071). No significant differences were seen in overall survival between groups., Conclusion: Our results suggest PPIs negatively affected recurrence-free survival in CapeOx-treated CRC patients and yielded no significant effects among FOLFOX-treated patients, potentially implicating a pharmacokinetic interaction between PPIs and capecitabine. No overall survival effects were seen. Given PPIs' widespread use, further studies are required to corroborate our findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Reversible late onset neutropenia associated with rituximab has been reported with incidence rates varying from 15 to 70% in B cell lymphoma patients receiving autologous stem cell transplantation. We conducted a retrospective descriptive study at one tertiary care center in adult B cell lymphoma patients treated with rituximab and autologous stem cell transplantation between 1 January 2004 and 30 June 2014. Late onset neutropenia was defined as an absolute neutrophil count <1.0 × 10 9  cells/L after neutrophil engraftment and less than six months post autologous stem cell transplantation. The primary objective was to determine the incidence of late onset neutropenia. The secondary objectives were to examine whether the use of rituximab with re-induction therapy, mobilization or high dose chemotherapy regimens increased the risk for late onset neutropenia, and to evaluate infectious complications. Of 315 subjects, 92 (29.2%) developed late onset neutropenia. Mobilization regimens containing rituximab (OR 2.90 95% CI: 1.31-6.40), high dose chemotherapy containing rituximab (OR 1.87 95% CI: 1.14-3.05), and exposure to rituximab in either or both regimens (OR 3.05 95% CI: 1.36-6.88) significantly increased the risk of late onset neutropenia. While neutropenic, 17.4% experienced an infection, 7.6% experienced febrile neutropenia, and 5.4% were hospitalized. In conclusion, rituximab with mobilization or high dose chemotherapy may increase the risk of late onset neutropenia post autologous stem cell transplantation.

We evaluated the effects of the non-psychoactive cannabinoid cannabidiol (CBD) on the inflammatory response and recovery of function following spinal cord injury (SCI). Female C57Bl/6 mice were exposed to spinal cord contusion injury (T9-10) and received vehicle or CBD (1.5 mg/kg IP) injections for 10 weeks following injury. The effect of SCI and CBD treatment on inflammation was assessed via microarray, qRT-PCR and flow cytometry. Locomotor and bladder function and changes in thermal and mechanical hind paw sensitivity were also evaluated. There was a significant decrease in pro-inflammatory cytokines and chemokines associated with T-cell differentiation and invasion in the SCI-CBD group as well as a decrease in T cell invasion into the injured cord. A higher percentage of SCI mice in the vehicle-treated group (SCI-VEH) went on to develop moderate to severe (0-65.9% baseline thermal threshold) thermal sensitivity as compared with CBD-treated (SCI-CBD) mice. CBD did not affect recovery of locomotor or bladder function following SCI. Taken together, CBD treatment attenuated the development of thermal sensitivity following spinal cord injury and this effect may be related to protection against pathological T-cell invasion., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose Elastomeric pumps are used to administer 46-hour infusions of 5-fluorouracil (5FU). Baxter suggests patients visually monitor their pumps to ensure that infusions are proceeding correctly. This can be confusing and lead to concerns about under- or over-dosing. Baxter has not considered weighing pumps as a validated method for monitoring. This study aims to validate weighing as a more accurate method for patients and healthcare professionals, and describe real life Baxter Infusor™ variability. Methods Patients who had been started on a 46-hour 5FU infusion returned to the clinic approximately 24 h after starting treatment. The pump was weighed on a StarFrit kitchen scale, and date, time, and weights recorded. Patients were asked if they had a preference for weighing or visually inspecting their pump. Results Pumps ( n = 103) were weighed between 17.25 and 27.5 h after connection. The average weight of a pump was 189 g. Of 103 pumps weighed, 99 weighed less than expected, corresponding to average flow rates of 5.69 mL/h over the elapsed time. The expected flow rate is 5 mL/h with 10% variability. Average flow rates within the 17.25- to 27.5-hour window were 4.561 mL/h, which is 8.78% slower than expected, but within the 10% known variability. Forty-seven percent of patients didn't have a preference for either method, but for those who did have a preference, more than twice as many preferred weighing. Conclusion With proper education, weighing Baxter Infusors at home with kitchen scales can be an accepted and objective alternative to the current recommendation of visual inspection.

Purpose Elastomeric pumps are used to infuse a 46-h fluorouracil protocol and patients are asked to visually inspect the pump daily. The pump has a variability of ±10% and there are additional patient variables that can increase this. The feasibility of weighing the pump rather than a visual inspection along with the secondary objective to confirm the pump's variability in real world conditions was undertaken. Methods Empty pumps were weighed using both pharmacy and kitchen scales. Pumps upon completion of the 46-h infusion were also weighed using both pharmacy and kitchen scales. Results The kitchen scale was as accurate as the pharmacy grade scale. Disconnected pumps showed the expected variability from using these infusor pumps along with a few showing greater variability likely due to patient variables. Conclusion Weighing pumps appears to be feasible both at the pharmacy and home level. Next steps would be to weigh pumps during the infusion to validate an alternate method to simple visual inspection for patients to confirm proper infusing of the pump at their home.

Aim: To identify cancer drugs amenable to strategies for reducing expenditure and avoiding drug wastage., Methods: Information was sourced from product information in 20 countries on parenteral cytotoxic agents, and cancer and noncancer monoclonal antibodies. Data were collected on vial sizes, overage, stability and presentation forms., Results: Vial size availability varied significantly between countries, with often only single vial sizes for numerous medications. Overage was poorly reported. Stability data were inconsistent and variable between countries, with most drugs only having a 24 h expiry. Three cancer-indicated monoclonal antibodies, thought suitable for prefilled syringe administration, were only available as vials., Conclusion: Many expensive cancer drugs are suitable for global cost-reduction strategies. Collaboration is vital to affecting change and reducing expenditure.

Background: Capecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin ± lapatinib in metastatic gastro-esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS., Methods: Early stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes., Results: Of 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non-PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005)., Conclusions: PPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Capecitabine is a highly water soluble prodrug of 5-fluorouracil that is dosed by patient body surface area. Body surface area dosing makes no allowances for differences in body composition. There is mounting evidence that lean body mass is a better predictor of toxicity than body surface area for drugs which distribute into the lean compartment. Because women, on average, have lower lean body mass than men, we expect that women would experience a higher incidence of toxicity than men when body surface area dosing is used., Objective: To determine whether female colorectal cancer patients experienced a higher incidence of dose-limiting toxicity than men when treated with adjuvant capecitabine., Methods: We conducted a retrospective chart review of colorectal cancer patients treated with adjuvant capecitabine at our institute between 2008 and 2012. Patients receiving capecitabine were identified from the pharmacy dispensing database and then screened for inclusion. Dosing and toxicity information were gathered and dose-limiting toxicity incidence (defined as a composite endpoint of dose delay, dose reduction, or discontinuation of therapy) was compared between males and females using the chi-square test. Binary logistic regression analysis was then performed to account for differences between male and female populations., Results: A total of 299 patients (163 males, 136 females) met inclusion criteria. Females had a significantly higher dose-limiting toxicity incidence than males (67.7 vs. 52.2%, p = 0.007). Relationships between gender and dose-limiting toxicity incidence remained significant after logistic regression analysis (OR: 2.04; 95% CI: 1.23-3.36)., Conclusion: Female colorectal cancer patients experience a higher dose-limiting toxicity incidence than male patients when given adjuvant capecitabine dosed according to body surface area., (© The Author(s) 2015.)

Background: Cost avoidance occurs when, because of provision of a drug therapy [drug cost avoidance (dca)] or a pathology test [pathology cost avoidance (pca)] during trial participation, health care payers need not pay for standard treatments or testing. The aim of our study was to estimate the total dca and pca for Canadian patients enrolled in relevant phase iii trials conducted by the ncic Clinical Trials Group., Methods: Phase iii trials that had completed accrual and resulted in dca or pca were identified. The pca was calculated based on the number of patients screened and the test cost. The dca was estimated based on patients randomized, the protocol dosing regimen, drug cost, median dose intensity, and median duration of therapy. Costs are presented in Canadian dollars. No adjustment was made for inflation., Results: From 1999 to 2011, 4 trials (1479 patients) resulted in pca and 17 trials (3195 patients) resulted in dca. The total pca was estimated at $4,194,849, which included testing for KRAS ($141,058), microsatellite instability ($18,600), and 21-gene recurrence score ($4,035,191). The total dca was estimated at $27,952,512, of which targeted therapy constituted 43% (five trials). The combined pca and dca was $32,147,361., Conclusions: Over the study period, trials conducted by the ncic Clinical Trials Group resulted in total cost avoidance (pca and dca) of approximately $7,518 per patient. Although not all trials lead to cost avoidance, such savings should be taken account when the financial impact of conducting clinical research is being considered.

Following a review of a chemotherapy medication adverse event where the incorrect medication was prepared by a pharmacy, a number of steps were taken to review the literature and best practice information related to checking processes for the preparation of parenteral chemotherapy. Concepts such as identification of critical stop check points, independent double checks, and human factors principles were reviewed and incorporated into newly designed chemotherapy preparation worksheets with embedded checklists. Usability testing and staff feedback during implementation revealed a number of key learning points that resulted in additional work to further improve the chemotherapy worksheets with embedded checklists and highlighted the need for a culture of continuous quality improvement., (© The Author(s) 2014.)

With their ability to catalyse the formation of phosphodiester linkages, DNA ligases and RNA ligases are essential tools for many protocols in molecular biology and biotechnology. Currently, the nucleic acid ligases from bacteriophage T4 are used extensively in these protocols. In this review, we argue that the nucleic acid ligases from Archaea represent a largely untapped pool of enzymes with diverse and potentially favourable properties for new and emerging biotechnological applications. We summarise the current state of knowledge on archaeal DNA and RNA ligases, which makes apparent the relative scarcity of information on in vitro activities that are of most relevance to biotechnologists (such as the ability to join blunt- or cohesive-ended, double-stranded DNA fragments). We highlight the existing biotechnological applications of archaeal DNA ligases and RNA ligases. Finally, we draw attention to recent experiments in which protein engineering was used to modify the activities of the DNA ligase from Pyrococcus furiosus and the RNA ligase from Methanothermobacter thermautotrophicus, thus demonstrating the potential for further work in this area.

Introduction: Chemotherapy-induced nausea and vomiting (CINV) has been shown to adversely impact patient anxiety, quality of life, treatment adherence, and use of health care resources. CINV control still remains a challenge, and lack of effective communication between the patient and clinician has been highlighted in the literature as the main barrier to optimal control. The Multinational Association of Supportive Care in Cancer (MASCC) has developed a tool (MASCC Antiemesis Tool (MAT)) to improve assessment and subsequent management of CINV by enhancing communication between patients and their clinicians. This study assessed the feasibility of using the MAT in patients at the Tom Baker Cancer Centre. The secondary objective was to describe the incidence of CINV as identified by the tool., Methods and Materials: This study involved a prospective survey using the MAT in patients receiving intravenous chemotherapy. Subjects completed the MAT twice post-chemotherapy regarding CINV symptoms and returned it at their next clinic appointment. Participants were also surveyed to evaluate feasibility with regard to using the MAT., Results: Of the 50 patients recruited, 56% returned surveys. The majority of patients reported that the MAT facilitated communication with their clinician, particularly those who had experienced CINV. Fifty-four percent of patients who returned the MAT reported CINV; however, less than half of them had received American Society of Clinical Oncology-recommended antiemetic regimens. Only four patients with CINV had antiemetic changes made for subsequent cycles., Conclusion: The MAT is a feasible tool which can improve communication of CINV symptoms between patients and clinicians, a foundational step toward improving CINV management., (© The Author(s) 2014.)

Introduction: Renal cell cancer is a chemotherapy-insensitive cancer treated by vascular endothelial growth factor receptor antagonists. Recently, a question has arisen on whether there is an interaction between tyrosine kinase inhibitors, such as sunitinib, and acid suppressing agents., Methods: A retrospective chart review was conducted for patients at two tertiary care centers who received sunitinib between 1 January 2006 and 31 March 2013. Using electronic systems and a province-wide electronic health records database, medication dispensing records were obtained. A univariate Cox's proportional hazard model determined if acid suppression had effects on progression-free survival and overall survival., Results: Of 383 patient charts reviewed, 231 were included in the study. Patients on intermittent acid suppression, lost to follow-up or received sunitinib for less than one week were excluded from the study. The median age of the study population was 65. Patients who received no acid suppression (n = 186) had a median progression-free survival of 23.6 weeks (95% CI, 19.0-31.9 weeks) and patients who received continuous acid suppression (n = 45) had a median progression-free survival of 18.9 weeks (95% CI, 11.0-23.7 p = 0.04). A median overall survival of 62.4 weeks (95% CI, 42.0-82.7 weeks) was observed in the group with no acid suppression, while a median overall survival of 40.9 weeks (95% CI, 26.1-74.4 weeks) was observed in the continuous acid suppression group (p = 0.02)., Conclusion: There was a significant difference in progression-free survival and overall survival between the acid suppressed and no acid suppression groups. Further research is required to confirm this potential interaction., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Purpose: The risk of medication errors with vincristine administration is well documented. Our objective was to ascertain how vincristine is administered worldwide and determine what strategies for preventing the accidental intrathecal administration of vincristine are in place., Methods: A survey, comprising 28 questions, was distributed to 363 International Society of Oncology Pharmacy Practitioners members from 42 countries via email. Questions were asked on methods of vincristine administration, intrathecal drug administration and strategies used to prevent medication errors. A reminder was sent and the survey was available on the International Society of Oncology Pharmacy Practitioners website. Only one survey per institution was requested., Results: In all, 62 responses from 15 countries were received, with the majority from Australia. Vincristine was dispensed in mini-bags in 77.4% of centres, though some also used syringes. Syringes were used in 31.1% of centres, with half these doses prepared undiluted. Administration took 5 to 15 minutes in most centres (78.8%). The most common reasons for still using syringes were perceived risk of extravasation and faster infusion time. Despite numerous vincristine administrations, extravasation was very rare. Other recommended strategies for error prevention were in use in the majority of centres., Conclusion: Comparisons with three previous surveys are difficult as the majority of respondents in those studies were from the USA. A number of areas appear to have improved, particularly the preparation of vincristine in mini-bags, but they are far from perfect. Deaths continue to occur following accidental intrathecal administration of vincristine. International Society of Oncology Pharmacy Practitioner members are urged to lead the way in incorporating strategies for prevention into institutions worldwide., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Oral tyrosine kinase inhibitors are the standard of care for chronic myeloid leukemia. Tyrosine kinase inhibitors are administered in an outpatient setting for an indefinite period which may negatively impact adherence. Non-adherence to tyrosine kinase inhibitors is associated with disease progression., Objectives: To evaluate the need for adherence-enhancing interventions, this study was designed to determine the proportion of chronic myeloid leukemia patients non-adherent to their tyrosine kinase inhibitor regimen. The secondary objective was to identify the influence of patient characteristics on tyrosine kinase inhibitor adherence., Methods: Cross-sectional retrospective chart and dispensing record reviews were performed to identify patients receiving a tyrosine kinase inhibitor from 1 June 2010 to 31 January 2012. Adherence was evaluated using the medication possession ratio., Results: A total of 124 patients were included. Thirty-eight (31%) patients were non-adherent to their tyrosine kinase inhibitor regimen. Patients not receiving concurrent medications were more likely to be non-adherent (odds ratio (OR) 2.33, 95% confidence interval (CI) 1.05-5.13, p=0.04). The median medication possession ratio was 0.95 (IQR=0.83-1.07). Median medication possession ratio was lower in patients receiving imatinib compared to dasatinib or nilotinib (0.95 vs. 1.00, p=0.01) and in those less than 50 years old compared to those greater than 50 years old (0.92 vs. 0.97, p=0.02)., Conclusions: Optimal tyrosine kinase inhibitor adherence in chronic myeloid leukemia patients poses a significant obstacle in achieving best possible outcomes while reducing healthcare costs. In this study, one in three chronic myeloid leukemia patients treated with a tyrosine kinase inhibitor were non-adherent to their regimen. Those at higher risk of non-adherence were on no concurrent medications, less than 50 years old, and those treated with imatinib. Active intervention to improve tyrosine kinase inhibitor adherence should be developed, implemented, and evaluated to improve patient outcomes at our center., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Erlotinib is a key therapy for advanced NSCLC. Concurrent AS therapy with TKIs might reduce TKI plasma levels. Because of gastroesophageal reflux disease prevalence, this retrospective analysis was undertaken to determine if coadministering erlotinib with AS therapy affected NSCLC outcomes., Patients and Methods: Records of advanced NSCLC patients who received erlotinib from 2007 to 2012 at a large, centralized, cancer institution were retrospectively reviewed. Pertinent demographic data were collected and concomitant AS treatment was defined as AS prescription dates overlapping with ≥ 20% of erlotinib treatment duration. Records of patients who received erlotinib for ≥ 1 week were analyzed for progression-free survival (PFS) and overall survival (OS)., Results: Stage IIIB/IV NSCLC patients (n = 544) were identified and 507 had adequate data for review. The median age was 64 years and 272 were female. Adenocarcinoma (n = 318; 64%) and squamous (n = 106; 21%) were predominant subtypes; 124 patients received concomitant AS therapy. In this unselected population, median PFS and OS in AS versus no AS groups were 1.4 versus 2.3 months (P < .001) and 12.9 versus 16.8 months (P = .003), respectively. Factoring sex, subtype, and performance status in multivariate Cox proportional hazards ratios for PFS and OS between AS and no AS groups were 1.83 (95% confidence interval [CI], 1.48-2.25) and 1.37 (95% CI, 1.11-1.69), respectively., Conclusion: This large population-based study suggests erlotinib efficacy might be linked with gastric pH and OS could be adversely affected. To our knowledge, this is the first study demonstrating a possible negative clinical effect of coadministration of erlotinib with AS therapy. Further prospective investigation is warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: A randomized trial carried out by Shepherd et al. in patients with advanced or metastatic non-small-cell lung cancer showed statistically significant benefit of erlotinib over placebo in prolonging overall survival and progression-free survival., Objectives: The primary outcome was to compare overall survival of patients treated with erlotinib for non-small-cell lung cancer at Alberta Health Services - Cancer Care to the overall survival seen in the pivotal trial. Secondary outcomes included comparing progression-free survival, overall response rate, and duration of response between the two patient populations., Methods: A retrospective review of charts was conducted for patients with locally advanced or metastatic non-small-cell lung cancer who received erlotinib therapy after failure of at least one prior chemotherapy regimen between 1 August 2006 and 31 July 2009. Survival data was analyzed using the Kaplan-Meier method., Results: Median overall survival and progression-free survival were 5.19 months and 2.46 months, respectively, in Alberta Health Services - Cancer Care patients. The rate of response was 11% (median duration of response, 6.7 months). The likelihood of a response to erlotinib was higher among nonsmokers (p < 0.0001) and those with response to prior chemotherapy (p = 0.0896). In multivariate analysis, good performance status (p = 0.0109) and response to prior therapy (p < 0.0001) were favorable factors for survival., Conclusions: In a clinical setting, erlotinib does not perform as well in terms of median overall survival as reported in the pivotal trial (5.19 vs. 6.70 months).

Purpose: To determine how many breast cancer patients who initiated adjuvant endocrine therapy discontinued early and to evaluate adherence in patients who persisted with therapy. Secondary objectives were to explore possible trends to see if certain factors may correlate to early discontinuation of therapy., Methods: A retrospective review of charts and pharmacy dispensing records was conducted, including patients who initiated adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute from 1 January to 31 December, 2006., Results: Out of 346 patients, 81 (22%) discontinued therapy within 2 years. Adherence rates calculated for the 265 patients who remained on therapy beyond 2 years showed that 247 (93%) of these patients had 80% or better adherence. Patients who did not undergo chemotherapy and patients with Cross Cancer Institute follow-up times of less than 1 year were significantly more likely to discontinue therapy early., Conclusions: The majority of patients who were prescribed adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute remained on therapy for at least 2 years and were adherent. Longer follow-up by Cross Cancer Institute practitioners may help decrease discontinuation rates.

Background: Radiotherapy with concomitant and adjuvant temozolomide has been the standard of care for newly diagnosed glioblastoma in adults since the pivotal trial by Roger Stupp and colleagues. The effectiveness of this regimen has not been evaluated in Canada. Additionally, the impact of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation on patient survival has not been confirmed. Hence, survival outcomes and MGMT predictive value were compared for the patients in Alberta versus the Stupp trial population., Methods: Retrospective chart review of 215 adult glioblastoma patients who started radiotherapy and temozolomide between January 2007 and December 2010 at the Cross Cancer Institute (Edmonton, Alberta) or the Tom Baker Cancer Centre (Calgary, Alberta)., Results: In the Alberta population, median overall survival was 14.3 months (vs. 14.6 months in trial, p = NS) and median progression-free survival was 5.8 months (vs. 6.9 months in trial, p = NS). However, unlike the trial, the Alberta MGMT subgroup analysis for overall survival was not statistically significant, despite a hazard ratio of 0.65 in favor of the methylated group. More Alberta patients received corticosteroids (p < 0.0001) and fewer underwent complete resection (p = 0.0001) or a postprogression second surgery (p = 0.01) than the Stupp population, but characteristics were otherwise similar., Conclusion: Current practice in Alberta enables patients to achieve overall and progression-free survival similar to the clinical trial. Further follow-up is required to confirm the predictive value of the MGMT assay. Until that is clarified or better treatments are developed, it is reasonable to continue offering this treatment regimen to patients regardless of MGMT methylation status.

Objective: To continue with workplace contamination monitoring in the Alberta Cancer Board (ACB) pharmacy practice environment., Setting: The ACB in the Canadian province of Alberta which includes two public tertiary centers and 19 associated community satellite sites based around the province in existing hospitals., Methods: After the completion of a Phase 1 and Phase 11 study,(1) which investigated the feasibility of routine monitoring of antineoplastic agent contamination in the pharmacy practice environment, it was decided to launch a Phase III study. The Phase III study would be done at the Cross Cancer Institute in the main pharmacy department as well as at a brand new satellite pharmacy within the CCI hospital. Samples would be taken in these areas as well as on the outer exterior of latex gloves worn to prepare cyclophosphamide and other antineoplastics., Results: The result determined that the area in front of the biological safety cabinet in the main CCI pharmacy department as well as the exterior of the latex gloves showed evidence of cyclophosphamide contamination. The results from the sample taken in the new satellite pharmacy showed no evidence of cyclophosphamide contamination., Conclusion: results from this study prompted a decision to launch a Phase IV study to determine the feasibility within our network, for routine monitoring as well as sampling throughout the clean room beyond the BSC.

Background: The Alberta Cancer Board is composed of 19 cancer centers in Alberta, Canada. In 1996, the Alberta Cancer Board's Medication Error Prevention Committee developed a medication error prevention survey based on the medication error prevention policies. Since 1996, this survey has been sent annually to the pharmacy departments of the 19 cancer centers. Each year, the results are presented to the Pharmacy and Therapeutics Committee of the Alberta Cancer Board., Objectives: The purpose of the paper was to present and analyze five years of medication error prevention survey results, thus summarizing adherence to the Alberta Cancer Board's medication error prevention policies., Methods: Medication error prevention survey results from 2003 to 2007 were collected. For each of the five years, a medication error prevention survey was faxed to the pharmacy department at each of the 19 cancer centers of the Alberta Cancer Board. Results of the survey were tabulated by the pharmacist responsible for quality assurance., Results: Analysis of the five years of medication error prevention survey results revealed that over 90% of the medication error prevention policies were followed within the 19 Alberta Cancer Board sites. Adherence to the policies was 490% in the tertiary sites and associate clinics. Adherence was also >90% in the community cancer centers., Conclusions: Results from the survey indicated that the medication error prevention policies are practiced within the Alberta Cancer Board. Potential areas of improvement have been identified and will be addressed by the Medication Error Prevention Team.

Background: The safe use of medications is a major concern in oncology practice. Three organizations collaborated on a survey to determine if practitioners had implemented current recommended safe practices for IV vincristine administration, general oncology safe practices, and safe practices for oral chemotherapy., Methods: A survey was distributed to members of the Hematology Oncology Pharmacy Association (HOPA) and the International Society of Pharmacy Practitioners (ISOPP) using Survey Monkey. The Institute of Safe Medication Practices (ISMP) also solicited readers of its Medication Safety Alert! to respond to the survey. A comparison to results from a survey conducted by ISMP in 2006 on safe practices for IV vincristine was also conducted., Results: The majority of respondents were aware of the WHO recommendations for IV vincristine, although the rate of implementation of the guidelines ranged from 24.1 to 53.6%. When compared to the ISMP 2006 survey there was a 25.8-37.4% improvement in following many of the safe practice guidelines. Administering IV vincristine via a minibag showed the lowest rate of adoption (less than 40%). Of the 35 survey items on general chemotherapy safety strategies, 80% of respondents had implemented at least 21 items in the survey. Overall 32.4% of respondents did not consider oral chemotherapy as requiring the same safety concerns as parenteral therapy., Conclusions: The results of this survey will provide a new baseline for the adoption rate of safe medication practice recommendations related to oncology. Further work on addressing barriers in adopting identified safe practice recommendations needs to be conducted.

Purpose: To design a tool to assist clinician participation with cancer drug funding decisions. Public policy-makers and insurers are struggling with funding decisions regarding increasingly expensive new cancer drugs. Increasingly, oncologists are contributing to the process of review that leads to such decisions. We were asked to design a system for ranking new cancer drugs for priority-based funding decisions., Methods: The "Accountability for Reasonableness" framework informed the design of a six-module multistakeholder decision process blending evidence-based traditional technology assessment methods with individual and cultural values elicitation. The tool was piloted in three settings: (1) videotaped simulated multistakeholder deliberation sessions; (2) clinical oncology leaders; and (3) a regional (Canadian provincial) pharmacy and therapeutics committee making formulary decisions. The modules involve: decision clarification, drug eligibility screening (filtering), clinical performance scoring index, cost modeling, data integration and values clarification, and process evaluation., Results: The tool was feasible to use, acceptable to participants, and able to rank candidate drugs. The pharmacy and therapeutics committee with whom it was tested used the tool as a part of their deliberations, and the tumor group leaders requested its incorporation into organization-based decision making., Conclusion: The decision tool can facilitate priority-based cancer drug funding decisions that meet the conditions of fairness as perceived by participants, including oncologists.

[reaction: see text] Fluorinated norbornene monomers exhibit the requisite properties for inclusion in 157 nm photoresists, but traditional addition and radical polymerizations with these monomers have failed. Norbornanediols provide an alternate route to these materials via condensation polymerization, and methods have been developed for the efficient synthesis of the exo-2-syn-7- and endo-2-exo-3-dihydroxynorbornanes. Synthesis of the fluorinated analogues is complicated by steric and electronic effects; however, a high-yielding synthesis of endo-2-exo-3-dihydroxynorbornane bearing a 5-endo-[2,2-bis(trifluoromethyl)hydroxyethyl] substituent is reported.