How do we achieve blinding in modern electronic and paper medical records during the conduct of transfusion trials?

BACKGROUND: Regulatory aspects of transfusion medicine add complexity in blinded transfusion trials when considering various electronic record keeping software and blood administration processes. The aim of this study is to explore strategies when blinding transfusion components and products in paper and electronic medical records. METHODS: Surveys were collected and interviews were conducted for 18 sites across various jurisdictions in North America to determine solutions applied in previous transfusion randomized control trials. RESULTS: Sixteen responses were collected of which 11 had previously participated in a transfusion randomized control trial. Various solutions were reported which were specific to the laboratory information system (LIS) and electronic medical record (EMR) combinations although solutions could be grouped into four categories which included the creation of a study product code in the LIS, preventing the transmission of data from the LIS to the EMR, utilizing specialized stickers and labels to conceal product containers and documents in the paper records, and modified bedside procedures and documentation. DISCUSSION: LIS and EMR combinations varied across sites, so it was not possible to determine combination-specific solutions. The study was able to highlight solutions that may be emphasized in future iterations of LIS and EMR software as well as procedural changes that may minimize the risk of unblinding.

Cationic Porphyrin-Based Ionic Nanomedicines for Improved Photodynamic Therapy.

This study presents the synthesis and characterization of monosubstituted cationic porphyrin as a photodynamic therapeutic agent. Cationic porphyrin was converted into ionic materials by using a single-step ion exchange reaction. The small iodide counteranion was replaced with bulky BETI and IR783 anions to reduce aggregation and enhance the photodynamic effect of porphyrin. Carrier-free ionic nanomedicines were then prepared by using the reprecipitation method. The photophysical characterization of parent porphyrin, ionic materials, and ionic nanomaterials, including absorbance, fluorescence and phosphorescence emission, quantum yield, radiative and nonradiative rate, and lifetimes, was performed. The results revealed that the counteranion significantly affects the photophysical properties of porphyrin. The ionic nanomaterials exhibited an increase in the reactive oxygen yield and enhanced cytotoxicity toward the MCF-7 cancer cell line. Examination of results revealed that the ionic materials exhibited an enhanced photodynamic therapeutic activity with a low IC50 value (nanomolar) in cancerous cells. These nanomedicines were mainly localized in the mitochondria. The improved light cytotoxicity is attributed to the enhanced photophysical properties and positive surface charge of the ionic nanomedicines that facilitate efficient cellular uptake. These results demonstrate that ionic material-based nanodrugs are promising photosensitizers for photodynamic therapy.

Impacts of COVID-19 and elective surgery cancellations on platelet supply and utilization in the Canadian Province of British Columbia.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the vulnerability of platelet supply and the uncertain impact of the resumption of elective surgery on utilization. We report the impact of COVID-19 on platelet supply and utilization across a large, integrated healthcare system in the Canadian province of British Columbia (BC). MATERIALS AND METHODS: Historical platelet use in BC by indication was compiled for fiscal year 2010/2011-2019/2020. Platelet collections, initial daily inventory and disposition data were assessed pre-COVID-19 (1 April 2018-15 March 2020) and for two COVID-19 time periods in BC: a shutdown phase with elective surgeries halted (16 March-17 May, 2020) and a renewal phase when elective surgeries resumed (18 May-27 September 2020); comparisons were made provincially and for individual health authorities. RESULTS: Historically, elective surgeries accounted for 10% of platelets transfused in BC. Initial daily supplier inventory increased from baseline during both COVID-19 periods (93/90 units vs. 75 units pre-COVID-19). During the shutdown phase, platelet utilization decreased 10.4% (41 units/week; p < 0.0001), and remained significantly decreased during the ensuing renewal period. Decreased platelet utilization was attributed to fewer transfusions during the shutdown phase followed by a decreased discard/expiry rate during the renewal phase compared to pre-COVID-19 (15.2% vs. 18.9% pre-COVID-19; p < 0.0001). Differences in COVID-19 platelet utilization patterns were noted between health authorities. CONCLUSION: Decreased platelet utilization was observed in BC compared to pre-COVID-19, likely due to a transient reduction in elective surgery as well as practice and policy changes triggered by pandemic concerns.

Adaptations of transfusion systems to the COVID-19 pandemic in British Columbia, Canada: Early experiences of a large tertiary care center and survey of provincial activities.

BACKGROUND: In March 2020, a state of emergency was declared to facilitate organized responses to the coronavirus disease 2019 (COVID-19) pandemic in British Columbia, Canada. Emergency blood management committees (EBMCs) were formed regionally and provincially to coordinate transfusion service activities and responses to possible national blood shortages. STUDY DESIGN AND METHODS: We describe the responses of transfusion services to COVID-19 in regional health authorities in British Columbia through a collaborative survey, contingency planning meeting minutes, and policy documents, including early trends observed in blood product usage. RESULTS: Early strategic response policies were developed locally in collaboration with members of the provincial EBMC and focused on three key areas: utilization management strategies, stakeholder engagement (collaboration with frequent users of the transfusion service, advance notification of potential inventory shortage plans, and development of blood triage guidance documents), and laboratory staffing and infection control procedures. Reductions in transfusion volumes were observed beginning in mid-March 2020 for red blood cells and platelets relative to the prepandemic baseline (27% and 26% from the preceding year, respectively). There was a slow gradual return toward baseline beginning one month later; no product shortage issues were experienced. CONCLUSION: Provincial collaborative efforts facilitated the development of initiatives focused on minimizing potential COVID-19-related disruptions in transfusion services in British Columbia. While there have been no supply issues to date, the framework developed early in the pandemic should facilitate timely responses to possible disruptions in future waves of infection.

Improved Photophysical Properties of Ionic Material-Based Combination Chemo/PDT Nanomedicine.

Herein, a cost-effective and prompt approach to develop ionic material-based combination nanodrugs for cancer therapy is presented. A chemotherapeutic (phosphonium) cation and photodynamic therapeutic (porphyrin) anion are combined using a single step ion exchange reaction. Afterward, a nanomedicine is prepared from this ionic materials-based combination drug using a simplistic strategy of reprecipitation. Improved photophysical characteristics such as a slower nonradiative rate constant, an enhanced phosphorescence emission, a longer lifetime, and a bathochromic shift in absorbance spectra of porphyrin are observed in the presence of a chemotherapeutic countercation. The photodynamic therapeutic activity of nanomedicines is investigated by measuring the singlet oxygen quantum yield using two probes. As compared to the parent porphyrin compound, the synthesized combination material showed a 2-fold increase in the reactive oxygen species quantum yield, due to inhibition of face-to-face aggregation of porphyrin units in the presence of bulky chemotherapeutic ions. The dark cytotoxicity of combination therapy nanomedicines in the MCF-7 (cancerous breast) cell line is also increased as compared to their corresponding parent compounds in vitro. This is due to the high cellular uptake of the combination nanomedicines as compared to that of the free drug. Further, selective toxicity toward cancer cells was acquired by functionalizing nanomedicine with folic acid followed by incubation with MCF-7 and MCF-10A (noncancerous breast). Light toxicity experiments indicate that the synthesized ionic nanomedicine shows a greater cell death than either parent drug due to the improved photophysical properties and effective combination effect. This facile and economical strategy can easily be utilized in the future to develop many other combination ionic nanomedicines with improved photodynamics.

Registration errors among patients receiving blood transfusions: a national analysis from 2008 to 2017.

BACKGROUND AND OBJECTIVES: The key first step for a safe blood transfusion is patient registration for identification and linking to past medical and transfusion history. In Canada, any deviation from standard operating procedures in transfusion is an error voluntarily reportable to a national database (Transfusion Error Surveillance System [TESS]). We used this database to characterize the subset of registration-related errors impacting transfusion care, including where, when and why the errors occurred, and to identify frequent high-risk errors. MATERIALS AND METHODS: A retrospective analysis was conducted on transfusion errors reported to TESS by sentinel reporting sites relating to patient registration and patient armbands, between 2008 and 2017. Free-text comments describing the error were coded to further categorize into common error types. The number of specimens received in the transfusion laboratory was used as the denominator for rates to allow for comparison between hospital sites. RESULTS: Five hundred and fifty-four registration errors were reported from 10 hospitals, for a global error rate of 5·4/10 000 samples (median 5·0 [interquartile range 3·7-7·0]). The potential severity was high in 85·7% of errors (n = 475). The patient experienced a consequence in 10·8% of errors (n = 60), but none resulted in patient harm. Rates varied widely and differed by nature across sites. Errors most commonly occurred in outpatient clinics or procedure units (n = 160, 28·8%) and in emergency departments (n = 130, 23·5%). CONCLUSION: Registration errors affect transfusion at every step and location in the hospital and are commonly high risk. Further research into common root causes is warranted to identify preventative strategies.

Optimizing Lignosulfonic Acid-Grafted Polyaniline as a Hole-Transport Layer for Inverted CH3NH3PbI3 Perovskite Solar Cells.

A conducting polymer of lignosulfonic acid-grafted, polyaniline-doped camphorsulfonic acid (LS-PANI-CSA), created via a low-temperature solution process, has been explored as an efficient hole-transport layer (HTL) for inverted single cation-anion CH3NH3PbI3 perovskite solar cells. The performance of the solar cell was optimized in this study by tuning the morphology and work function of LS-PANI-CSA films using dimethylsulfoxide (DMSO) as a solvent in treatment. Results showed that DMSO washing enhanced the electronic properties of the LS-PANI-CSA film and increased its hydrophobicity, which is very important for perovskite growth. The perovskite active layer deposited onto the DMSO-treated LS-PANI-CSA layer had higher crystallinity with large grain sizes (>5 µm), more uniform and complete surface coverage, and very low pinhole density and PbI2 residues compared to untreated LS-PANI-CSA. These enhancements result in higher device performance and stability. Using DMSO-treated LS-PANI-CSA as an HTL at 15 nm of thickness, a maximum 10.8% power conversion efficiency was obtained in ITO/LS-PANI-CSA/MAPbI3/PCBM/BCP/Ag inverted-device configurations. This was a significant improvement compared to 5.18% for devices based on untreated LS-PANI-CSA and a slight improvement over PEDOT:PSS-based devices with 9.48%. Furthermore, the perovskite based on treated LS-PANI-CSA showed the higher stability compared to both untreated LS-PANI-CSA and PEDOT:PSS HTL-based devices.

Sample collection and sample handling errors submitted to the transfusion error surveillance system, 2006 to 2015.

BACKGROUND: In Canada, transfusion-related errors are voluntarily reported to a tracking system with the goal to systematically improve transfusion safety. This report provides an analysis of sample collection (SC) and sample handling (SH) errors from this national error-tracking system. STUDY DESIGN AND METHODS: Errors from 2006 to 2015 from 23 participating sites were extracted. A survey was conducted to obtain information regarding institutional policies. Samples received in the blood bank were used to calculate rates. "Wrong blood in tube" (WBIT) errors are blood taken from wrong patient and labeled with intended patient's information, or blood taken from intended patient but labeled with another patient's information. RESULTS: A total of 42,363 SC and 14,666 SH errors were reported. Predefined low-severity (low potential for harm) and high-severity errors (potential for fatal outcomes) increased from 2006 to 2015 (low SC, SH: 13-27, 3-12 per 1000; high SC, SH: 1.9-3.7, 0.5-2.0 per 1000). The WBIT rate decreased from 12 to 5.8 per 10,000 between 2006 and 2015 (p < 0.0001). The overall WBIT rate was 6.2 per 10,000, with variability by site (median, 0.3 per 10,000; range, 0-17 per 10,000). Sites with error detection mechanisms, such as regrouping second sample requirements, had lower error rates than sites that did not (SC, SH: 12, 1 per 1000 samples vs. 17, 3 per 1000 samples; p < 0.0001). CONCLUSION: WBIT rates decreased significantly. Low-severity error rates are climbing likely due to increased ascertainment and reporting. Prevention studies are necessary to inform changes to blood transfusion standards to eliminate these errors.

Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma.

Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88L265P, EZH2Y641F , and EZH2Y641N . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*02:01. Peripheral blood T cells were primed with peptide-loaded dendritic cells (DC), and reactive T cells were assessed for recognition of naturally processed mutant versus wild type full-length proteins. After screening three driver mutations across 17-26 HLA class I alleles and 3 × 106-3 × 107 T cells per donor, we identified CD4+ T cells against EFISENCGEII from EZH2Y641N (presented by HLA-DRB1*13:02) and CD8+ T cells against RPIPIKYKA from MYD88L265P (presented by HLA-B*07:02). We failed to detect RPIPIKYKA-specific T cells in seven other HLA-B*07:02-positive donors, including two lymphoma patients. Thus, healthy donors harbor T cells specific for common driver mutations in lymphoma. However, such responses appear to be rare due to the combined limitations of antigen processing, HLA restriction, and T cell repertoire size, highlighting the need for highly individualized approaches for selecting targets.

Physical activity, obesity and survival in diffuse large B-cell and follicular lymphoma cases.

There is limited information concerning the impact of physical activity and obesity on non-Hodgkin lymphoma (NHL) prognosis. We examined the associations between pre-diagnosis physical activity and body mass index (BMI) with survival in 238 diffuse large B-cell (DLBCL) and 175 follicular lymphoma cases, with follow-up from 2000 to 2015. The most physically active DLBCL cases had 41% lower risk of dying in the follow-up period than the least active [Hazard ratio (HR) = 0·59, 95% confidence interval (CI) = 0·36-0·96], while obese follicular lymphoma cases had a 2·5-fold risk of dying (HR = 2·52, 95% CI = 1·27-5·00) compared with cases with normal BMI. NHL-specific survival results were similar.

Standardized Direct Observation Assessment Tool: Using a Training Video.

BACKGROUND: We developed a DVD training tool to educate physicians evaluating emergency residents on accurate Standardized Direct Observation Assessment Tool (SDOT) application. OBJECTIVE: Our goal was to assess whether this training video improved attendings' and senior residents' SDOT use. METHODS: Participants voluntarily completed SDOT evaluations based on a scripted "test" video. A DVD with "positive" and "negative" scenarios of proper SDOT use was viewed. It included education on appropriate recording of 26 behaviors. The test scenario was viewed again and follow-up SDOTs submitted. Performances by attendings and residents on the pre- and post-test SDOTs were compared. RESULTS: Twenty-six attendings and 26 senior residents participated. Prior SDOT experience was noted for 8 attendings and 11 residents. For 20 anchors, participants recorded observed behaviors with statistically significant difference on one each of the pretest (no. 20; p = 0.034) and post-test (no. 14; p = 0.041) SDOTs. On global competency assessments, pretest medical knowledge (p = 0.016) differed significantly between groups. The training intervention changed one anchor (no. 5; p = 0.035) and one global assessment (systems-based practice; p = 0.031) more negatively for residents. Recording SDOTs with exact agreement occurred 48.73% for attendings pretest and 54.41% post-test; resident scores were 45.86% and 49.55%, respectively. DVD exposure slightly raised attending scores (p = 0.289) and significantly lowered resident scores (p = 0.046). CONCLUSIONS: Exposure to an independently developed SDOT training video tended to raise attending scores, though without significance, while at the same time lowered senior resident scores statistically significantly. Emergency attendings' and senior residents' SDOT scoring rarely differed with significance; about half of anchor behaviors were recorded with exact agreement. This suggests senior residents, with appropriate education, may participate in SDOT assessment.

Soft-shear induced phase-separated nanoparticle string-structures in polymer thin films.

Application of shear stress has been shown to unidirectionally orient the microstructures of block copolymers and polymer blends. In the present work, we study the phase separation of a novel nanoparticle (NP)-polymer blend thin film system under shear using a soft-shear dynamic zone annealing (DZA-SS) method. The nanoparticles are densely grafted with polymer chains of chemically dissimilar composition from the matrix polymer, which induces phase separation upon thermal annealing into concentrated nanoparticle domains. We systematically examine the influence of DZA-SS translation speed and thus the effective shear rate on nanoparticle domain elongation and compare this with the counterpart binary polymer blend behavior. Unidirectionally aligned nanoparticle string-domains are fabricated in the presence of soft-shear in confined thin film geometry. We expect this DZA-SS method to be applicable to various NP-polymer blends towards unidirectionally aligned nanoparticle structures, which are important to functional nanoparticle structure fabrication.

Toward Personalized Lymphoma Immunotherapy: Identification of Common Driver Mutations Recognized by Patient CD8+ T Cells.

PURPOSE: A fundamental challenge in the era of next-generation sequencing (NGS) is to design effective treatments tailored to the mutational profiles of tumors. Many newly discovered cancer mutations are difficult to target pharmacologically; however, T-cell-based therapies may provide a valuable alternative owing to the exquisite sensitivity and specificity of antigen recognition. To explore this concept, we assessed the immunogenicity of a panel of genes that are common sites of driver mutations in follicular lymphoma, an immunologically sensitive yet currently incurable disease. EXPERIMENTAL DESIGN: Exon capture and NGS were used to interrogate tumor samples from 53 patients with follicular lymphoma for mutations in 10 frequently mutated genes. For 13 patients, predicted mutant peptides and proteins were evaluated for recognition by autologous peripheral blood T cells after in vitro priming. RESULTS: Mutations were identified in 1-5 genes in 81% (43/53) of tumor samples. Autologous, mutation-specific CD8(+) T cells were identified in 23% (3/13) of evaluated cases. T-cell responses were directed toward putative driver mutations in CREBBP and MEF2B. Responding T cells showed exquisite specificity for mutant versus wild-type proteins and recognized lymphoma cells expressing the appropriate mutations. Responding T cells appeared to be from the naïve repertoire, as they were found at low frequencies and only at single time points in each patient. CONCLUSIONS: Patients with follicular lymphoma harbor rare yet functionally competent CD8(+) T cells specific for recurrent mutations. Our results support the concept of using NGS to design individualized immunotherapies targeting common driver mutations in follicular lymphoma and other malignancies. Clin Cancer Res; 22(9); 2226-36. ©2015 AACR.

Comparative Aging Study of Organic Solar Cells Utilizing Polyaniline and PEDOT:PSS as Hole Transport Layers.

The aging effect on P3HT:PCBM organic solar cells was investigated with camphorsulfonic doped polyaniline (PANI:CSA) or poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) used as the hole transport layer (HTL). The cells were encapsulated and exposed to a continuous normal atmosphere on a dark shelf and then characterized intermittently for more than two years. The photovoltaic results revealed that the cells with PEDOT: PSS HTL showed better initial results than the cells with PANI:CSA HTL. Over time, PEDOT: PSS-based cells exhibited faster degradation than PANI:CSA-based cells, where the average efficiency of six cells dropped to zero in less than one and a half years. On the other hand, PANI:CSA-based cells exhibited a much more stable performance with an average efficiency drop of only 15% of their initial values after one and a half years and 63% after two years. A single-diode model was utilized to fit the experimental data with the theoretical curve to extract the diode parameters, such as the ideality factor, to explain the effect of aging on the diode's performance.

Ammonia gas sensing behavior of tanninsulfonic acid doped polyaniline-TiO2 composite.

A highly active tannin doped polyaniline-TiO2 composite ammonia gas sensor was developed and the mechanism behind the gas sensing activity was reported for the first time. A tanninsulfonic acid doped polyaniline (TANIPANI)-titanium dioxide nanocomposite was synthesized by an in situ polymerization of aniline in the presence of tanninsulfonic acid and titanium dioxide nanoparticles. X-ray diffraction and thermogravimetric analysis were utilized to determine the incorporation of TiO2 in TANIPANI matrix. UV-Visible and infrared spectroscopy studies provided information about the electronic interactions among tannin, polyaniline, and TiO2. Scanning electron microscopy (SEM) along with energy dispersive X-ray spectroscopy (EDS) and atomic force microscopy (AFM) surface analysis techniques were used to investigate the metal oxide dispersions inside polyaniline matrix. Gas sensors were prepared by spin coating solutions of TANIPANI-TiO2 and TANIPANI composites onto glass slides. Sensors were tested at three different concentrations (20 ppm, 40 ppm, and 60 ppm) of ammonia gas at ambient temperature conditions by measuring the changes in surface resistivity of the films with respect to time. Ammonia gas sensing plots are presented showing the response values, response times and recovery times. The TANIPANI-TiO2 composite exhibited better response and shorter recovery times when compared to TANIPANI control and other polyaniline composites that have been reported in the literature. For the first time a proposed mechanism of gas sensing basing on the polaron band localization and its effects on the gas sensing behavior of polyaniline are reported.