Comparison of Perceived Importance and Performance of Community Pharmacists' Role in South Korea During the Coronavirus Disease 2019 Pandemic.

OBJECTIVE: This study aimed to identify the roles of community pharmacists (CPs) during the coronavirus disease 2019 (COVID-19) pandemic, the differences in their role performance compared with their perceived importance, and limiting factors. METHODS: A cross-sectional online survey of CPs was conducted. The CPs self-measured the importance and performance of each role during the pandemic using a 5-point Likert scale. A paired t-test was used to compare each role's importance and performance scores. A logistic regression analysis of the roles with low performance scores, despite their level of importance, was conducted to determine the factors affecting performance. The limiting factors were also surveyed. RESULTS: The 436 responses to the questionnaire were analyzed. The performance scores were significantly lower than the perceived importance scores for 15 of the 17 roles. The source and update frequency of COVID-19 information and participation in outreach pharmaceutical services were associated with low performance scores. Insufficient economic compensation, the lack of communication channels, and legal limitations were the limiting factors in performing the CPs' roles. CONCLUSIONS: The participation in outreach pharmaceutical services, economic compensation, and communication channel should be improved to motivate the CPs in performing their roles.

Comparative Safety Profiles of Oncology Biosimilars: A Systematic Review and Network Meta-analysis.

BACKGROUND: It is crucial that the safety profiles of biosimilars are similar to those of the original biologics. A better understanding of biosimilars and their relative safety and immunogenicity profiles are required for healthcare providers to prescribe them to patients with life-threatening cancer diseases who receive chemotherapies with potentially serious adverse events (AEs). OBJECTIVES: The purpose of this study was to collate and analyze currently available safety and immunogenicity outcomes of biosimilars used in oncology and compare their safety information with those of the original biologics. METHODS: The MEDLINE and Cochrane Library databases were searched as at 28 February 2022. Four anti-cancer biosimilar molecules were considered: bevacizumab, trastuzumab, rituximab, and (peg)filgrastim. Through a systematic review, we selected the randomized controlled trials (RCTs) comparing safety outcomes between the biosimilars and original biologics of the four molecules. As safety outcomes, various treatment-emergent adverse events (TEAEs) were collated, such as any TEAE, serious AE, and TEAE higher than grade 3. A risk ratio (RR) per category of TEAE was estimated through a meta-analysis. A network meta-analysis (NMA) was also conducted to compare the safety among the biosimilar brands for TEAEs over 25% with higher variability in addition to the serious AE cases. RESULTS: Forty-nine RCTs were identified. The results from the meta-analysis showed that the safety and immunogenicity profiles of all four biosimilar molecules are comparable with that of the original biologics at the TEAE level without statistically significant differences, except for diarrhea for (peg)filgrastim. The incidence of diarrhea with (peg)filgrastim was less than that with the original biologic (RR 0.66, 95% confidence interval 0.50-0.89). The NMA results showed similar safety profiles among the biosimilar brands for all four biosimilar molecules, except for the serious adverse event of a trastuzumab biosimilar (RR 0.296, 95% credible interval 0.109-0.840). CONCLUSION: The meta-analysis and NMA for all four biosimilars showed that the safety and immunogenicity profiles of biosimilar products in oncology are generally comparable with that of the original biologics at the TEAE level. However, additional evidence needs to be collected since several TEAEs of specific biosimilars were out of the equivalent range. The results of this study provide comparative safety information and a better understanding of oncology biosimilars for healthcare providers to prescribe them to patients.

Quantitative Benefit-Risk Assessment of COVID-19 Vaccines Using the Multi-Criteria Decision Analysis.

In the early SARS-CoV-2 (COVID-19) pandemic, four major vaccines were approved despite limited efficacy and safety data through short regulatory review periods. Thus, it is necessary to assess the benefit-risk (BR) profiles of the COVID-19 vaccines. We conducted a quantitative BR assessment for four COVID-19 vaccines (mRNA-based: mRNA-1273 and BNT162b2; viral vector-based: Ad26.COV.2 and ChAdOx1-S) using multi-criteria decision analysis. Three benefit criteria and two risk criteria were considered: preventing COVID-19 infection for (1) adults aged ≥18 years; (2) seniors aged 60 years or older; and (3) severe COVID-19, adverse events (AEs), and serious AEs. Data were retrieved from clinical trials, observational studies, and county-specific AE monitoring reports. Based on the collected data, vaccines were scored for each criterion. 22 professionals weighted each criterion. The overall BR score was calculated using scores and weights. mRNA-1273 was the most preferred vaccine in pre-authorization and BNT162b2 in post-authorization. We found that the mRNA vaccine had a good balance between the benefits and risks. Using this BR assessment, the benefit-risk profile of COVID-19 vaccines can be updated with cumulated data. It will contribute to building evidence for decision making by policy makers and health professionals.

Immune-privileged embryonic Swiss mouse STO and STO cell-derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines.

Embryonic mouse STO (S, SIM; T, 6-thioguanine resistant; O, ouabain resistant) and 3(8)21-enhanced green fluorescent protein (EGFP) cell lines exhibit long-term survival and hepatic progenitor cell behaviour after xenogeneic engraftment in non-immunosuppressed inbred rats, and were previously designated major histocompatibility complex (MHC) class I- and class II-negative lines. To determine the molecular basis for undetectable MHC determinants, the expression and haplotype of H-2K, H-2D, H-2L and I-A proteins were reassessed by reverse transcriptase-polymerase chain reaction (RT-PCR), cDNA sequencing, RNA hybridization, immunoblotting, quantitative RT-PCR (QPCR), immunocytochemistry and flow cytometry. To detect cell differentiation (CD) surface antigens characteristic of stem cells, apoptotic regulation or adaptive immunity that might facilitate progenitor cell status or immune privilege, flow cytometry was also used to screen untreated and cytokine [interferon (IFN)-gamma]-treated cultures. Despite prior PCR genotyping analyses suggestive of H-2q haplotypes in STO, 3(8)21-EGFP and parental 3(8)21 cells, all three lines expressed H-2K cDNA sequences identical to those of d-haplotype BALB/c mice, as well as constitutive and cytokine-inducible H-2K(d) determinants. In contrast, apart from H-2L(d[LOW]) display in 3(8)21 cells, H-2Dd, H-2Ld and I-Ad determinants were undetectable. All three lines expressed constitutive and cytokine-inducible CD34; however, except for inducible CD117([LOW]) expression in 3(8)21 cells, no expression of CD45, CD117, CD62L, CD80, CD86, CD90.1 or CD95L/CD178 was observed. Constitutive and cytokine-inducible CD95([LOW]) expression was detected in STO and 3(8)21 cells, but not in 3(8)21-EGFP cells. MHC (class I(+[LOW])/class II-) and CD (CD34+/CD80-/CD86-/CD95L-) expression patterns in STO and STO cell-derived progenitor cells resemble patterns reported for human embryonic stem cell lines. Whether these patterns reflect associations with mechanisms that are regulatory of immune privilege or functional tissue-specific plasticity is unknown.

Embryonic mouse STO cell-derived xenografts express hepatocytic functions in the livers of nonimmunosuppressed adult rats.

Cells derived from embryonic mouse STO cell lines differentiate into hepatocytes when transplanted into the livers of nonimmunosuppressed dipeptidylpeptidase IV (DPPIV)-negative F344 rats. Within 1 day after intrasplenic injection, donor cells moved rapidly into the liver and were found in intravascular and perivascular sites; by 1 month, they were intrasinusoidal and also integrated into hepatic plates with approximately 2% efficiency and formed conjoint bile canaliculi. Neither donor cell proliferation nor host inflammatory responses were observed during this time. Detection of intrahepatic mouse COX1 mitochondrial DNA and mouse albumin mRNA in recipient rats indicated survival and differentiation of donor cells for at least 3 months. Mouse COX1 targets were also detected intrahepatically 4-9 weeks after STO cell injection into nonimmunosuppressed wild-type rats. In contrast to STO-transplanted rats, mouse DNA or RNA was not detectable in untreated or mock-transplanted rats or in rats injected with donor cell DNA. In cultured STO donor cells, DPPIV and glucose-6-phosphatase activities were observed in small clusters; in contrast, mouse major histocompatibility complex class I H-2Kq, H-2Dq, and H-2Lq and class II I-Aq markers were undetectable in vitro before or after interferon gamma treatment. Together with H-2K allele typing, which confirmed the Swiss mouse origin of the donor cells, these observations indicate that mouse-derived STO cell lines can differentiate along hepatocytic lineage and engraft into rat liver across major histocompatibility barriers.

Derivation and study of human epithelial cell lines resistant to killing by chromium trioxide.

CrO3 is cytotoxic for human epithelial 293 kidney cells over a narrow concentration range of approximately 2-8 microM (D50 approximately 3.0 microM); significantly greater toxicity is observed in clonogenic assays (D50 approximately 0.1-1.0 microM). Survival of a small fraction of cells (< or = 0.1%) at CrO3 concentrations between 10(-5) to 10(-3) M, and first-order kinetics of cytotoxicity, rationalized the derivation of a new panel of transformed human epithelial cell lines resistant to cytotoxic concentrations of CrO3 over the range of 5-100 microM. Wild-type and Cr-resistant 293 cell lines display similar morphology under phase microscopy, but wild-type cells grow faster and reach stationary phase sooner than Cr-resistant cells. The Cr-resistant phenotype is stable, and it is specific, since Cr-resistant cells are killed by NiSO4 or by CdCl2 at concentrations equivalent to those that kill wild-type cells. Toxicity analysis curves subjected to target theory suggest that the Cr-resistant cell lines have fewer Cr-sensitive "targets" and have undergone a "loss of function" compared to wild-type cells. This loss of function may be related to significantly lower rates of uptake of Na2(51)CrO4,which correlate inversely with CrO3 concentrations used for the selection and maintenance of the Cr-resistant lines, and to reduced levels of an approximately 96-kDa protein in comparison to wild-type cells. This new panel of Cr-resistant transformed human epithelial kidney cell lines will be useful in comparative studies of genetic resistance and sensitivity to human Cr(VI) toxicity, sulfate transport, and growth control differences between wild-type and Cr-resistant cells.

Nonlinear optical and two-photon absorbtion properties of 1,3,5-tricyano-2,4,6-tris(styryl)benzene-containing octupolar oligomers.

Octupolar oligomers containing 2-12 molecules of 1,3,5-tricyano-2,4,6-tris(styryl)benzene derivatives have been synthesized and their nonlinear optical and two-photon absorption (TPA) properties were determined. The beta(0) values are in the range of (85-1219) x 10(-30) esu and increase monotonically with the increasing number of the octupolar units within the molecule. The two-photon-induced fluorescence excitation spectra are quite similar to the single-photon absorption spectra except that the wavelength is doubled, indicating that the one- and two-photon allowed excited states are the same. The peak TPA cross-section values (delta(max)) measured with nanosecond pulses by the two-photon-induced fluorescence method are in the range (3010-62, 930) x 10(-50) cm(4)s photon(-1). The delta(max) increases as the number of the octupolar units in the molecules increases. A linear relationship is observed between delta(max) and beta, and this delta-beta relationship serves as a useful design strategy for the synthesis of novel octupolar oligomers and polymers with large TPA and beta.

Synthesis and nonlinear optical properties of 1,3,5-methoxy-2,4,6-tris(styryl)benzene derivatives.

[reaction: see text] Novel two-dimensional octupoles containing donors at the core and acceptors at the edge of peripheral groups were synthesized by Horner-Wittig reactions. These chromophores show very large first hyperpolarizability and good thermal stability and are attractive candidates for nonlinear optical materials.