Improving Pharmacy Students' Clinical Knowledge on Providing Care for Patients Belonging to the LGBTQ+ Community.

A 12-question survey instrument was developed, pilot-tested, and administered to 191 pharmacy students in their first professional year after engaging in a learning activity focusing on topics across five categories with clinical relevance to providing care to the LGBTQ+ community. A paired student t-test was performed on survey tool pre-test and post-test survey responses, with p < 0.05 considered significant. A total of 183 usable pre-test and post-test survey responses were received. Statistically significant differences between the pre-test and post-test correct responses were observed for scenarios involving proper pronoun use, hormone therapy (HT) counseling, immunization best practices, and communication hesitancy. The greatest knowledge change was reported in the categories of immunization best practices (48.9%), HT counseling (33.6%), and pronoun use (22.8%). Active learning assignments are effective teaching strategies to promote clinical knowledge in providing inclusive and culturally competent care to LGBTQ+ patients. Clinical topic areas including proper pronoun use, HT counseling, immunization best practices, privacy, risk awareness, and communication hesitancy are effective curricula additions for pharmacy colleges to advance inclusive curricula concerning providing care to the LGBTQ+ community.

Optimizing Drug-Drug Interaction Alerts Using a Multidimensional Approach.

OBJECTIVES: Excessive alerts are a common concern associated with clinical decision support systems that monitor drug-drug interactions (DDIs). To reduce the number of low-value interruptive DDI alerts at our hospital, we implemented an iterative, multidimensional quality improvement effort, which included an interdisciplinary advisory group, alert metrics, and measurement of perceived clinical value. METHODS: Alert data analysis indicated that DDIs were the most common interruptive medication alert. An interdisciplinary alert advisory group was formed to provide expert advice and oversight for alert refinement and ongoing review of alert data. Alert data were categorized into drug classes and analyzed to identify DDI alerts for refinement. Refinement strategies included alert suppression and modification of alerts to be contextually aware. RESULTS: On the basis of historical analysis of classified DDI alerts, 26 alert refinements were implemented, representing 47% of all alerts. Alert refinement efforts resulted in the following substantial decreases in the number of interruptive DDI alerts: 40% for all clinicians (22.9-14 per 100 orders) and as high as 82% for attending physicians (6.5-1.2 per 100 orders). Two patient safety events related to alert refinements were reported during the project period. CONCLUSIONS: Our quality improvement effort refined 47% of all DDI alerts that were firing during historical analysis, significantly reduced the number of DDI alerts in a 54-week period, and established a model for sustained alert refinements.

A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens.

This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines.

Voriconazole plasma concentrations in immunocompromised pediatric patients vary by CYP2C19 diplotypes.

AIM: Our objective was to describe the association between voriconazole concentrations and CYP2C19 diplotypes in pediatric cancer patients, including children homozygous for the CYP2C19*17 gain-of-function allele. MATERIALS & METHODS: A linear mixed effect model compared voriconazole dose-corrected trough concentrations (n = 142) among CYP2C19 diplotypes in 33 patients (aged 1-19 years). Voriconazole pharmacokinetics was described by a two-compartment model with Michaelis-Menten elimination. RESULTS: Age (p = 0.05) and CYP2C19 diplotype (p = 0.002) were associated with voriconazole concentrations. CYP2C19*17 homozygotes never attained therapeutic concentrations, and had lower dose-corrected voriconazole concentrations (median 0.01 µg/ml/mg/kg; p = 0.02) than CYP2C19*1 homozygotes (median 0.07 µg/ml/mg/kg). Modeling indicates that higher doses may produce therapeutic concentrations in younger children and in those with a CYP2C19*17/*17 diplotype. CONCLUSION: Younger age and the presence of CYP2C19 gain-of-function alleles were associated with subtherapeutic voriconazole concentrations. Starting doses based on age and CYP2C19 status could increase the number of patients achieving therapeutic voriconazole exposure.

Limb swelling in a pediatric sickle cell patient after revaccination with pneumococcal vaccine.

CASE (DESCRIPTION): This report describes an incident of limb swelling after revaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). A 5-year old female with sickle cell disease experienced severe arm swelling with edema to the extent that it was difficult to put a shirt over the arm. The day prior, she received PPSV23 concomitantly with the meningococcal vaccine. She had received the PPSV23 vaccine 2.5 years prior to the event. The patient was managed with analgesics, antiemetics, and antibiotic prophylaxis and the arm swelling resolved 24 h later. A decreased length of time between revaccination and concurrent administration with the meningococcal vaccine could have contributed. CONCLUSION: Although rare, limb swelling after revaccination could be a concern in special at-risk populations where repeated vaccination is necessary for pneumococcal protection.

Modified opsonization, phagocytosis, and killing assays to measure potentially protective antibodies against pneumococcal surface protein A.

The standard opsonophagocytosis killing assay (OPKA) for antibodies to pneumococcal capsular polysaccharide was modified to permit an evaluation of the protection-mediating antibodies to pneumococcal surface protein A (PspA). We found that by increasing the incubation time with the complement and phagocytes from 45 min to 75 min, the protective activity was readily detected. In another modification, we used a capsule type 2 target strain that expressed PspA but not pneumococcal surface protein C (PspC). With these modifications separately or in combination, rabbit antisera to the recombinant α-helical or proline-rich domains of PspA mediated >50% killing of the target strain. The ability of normal human sera to mediate the killing of pneumococci in this modified OPKA correlated with their levels of antibodies to PspA and their ability to protect mice against fatal infection with a type 3 strain. Passive protection of mice against pneumococci and killing in the modified OPKA were lost when normal human sera were adsorbed with recombinant PspA (rPspA) on Sepharose, thus supporting the potential utility of the modified OPKA to detect protective antibodies to PspA. In the standard OPKA, monoclonal antibodies to PspA were strongly protective in the presence of subprotective amounts of anti-capsule. Thus, the currently established high-throughput OPKA for antibodies to capsule could be modified in one of two ways to permit an evaluation of the opsonic efficacy of antibodies to PspA.

The proline-rich region of pneumococcal surface proteins A and C contains surface-accessible epitopes common to all pneumococci and elicits antibody-mediated protection against sepsis.

Pneumococcal surface protein A (PspA) and PspC of Streptococcus pneumoniae are surface virulence proteins that interfere with complement deposition and elicit protective immune responses. The C-terminal halves of PspA and PspC have some structural similarity and contain highly cross-reactive proline-rich (PR) regions. In many PR regions of PspA and PspC, there exists an almost invariant nonproline block (NPB) of about 33 amino acids. Neither the PR regions nor their NPB exhibit the alpha-helical structure characteristic of much of the protection-eliciting N-terminal portions of PspA and PspC. Prior studies of PspA and PspC as immunogens focused primarily on the alpha-helical regions of these molecules that lack the PR and NPB regions. This report shows that immunization with recombinant PR (rPR) molecules and passive immunization with monoclonal antibodies reactive with either NPB or PR epitopes are protective against infection in mice. PR regions of both PspA and PspC were antibody accessible on the pneumococcal surface. Our results indicate that while PspA could serve as a target of these protective antibodies in invasive infections, PspC might not. When antibody responses to rPR immunogens were evaluated by using flow cytometry to measure antibody binding to live pneumococci, it was observed that the mice that survived subsequent challenge produced significantly higher levels of antibodies reactive with exposed PR epitopes than the mice that became moribund. Due to their conservation and cross-reactivity, the PR regions and NPB regions represent potential vaccine targets capable of eliciting cross-protection immunity against pneumococcal infection.

Caenorhabditis elegans mutants resistant to attachment of Yersinia biofilms.

The detailed composition and structure of the Caenorhabditis elegans surface are unknown. Previous genetic studies used antibody or lectin binding to identify srf genes that play roles in surface determination. Infection by Microbacterium nematophilum identified bus (bacterially unswollen) genes that also affect surface characteristics. We report that biofilms produced by Yersinia pestis and Y. pseudotuberculosis, which bind the C. elegans surface predominantly on the head, can be used to identify additional surface-determining genes. A screen for C. elegans mutants with a biofilm absent on the head (Bah) phenotype identified three novel genes: bah-1, bah-2, and bah-3. The bah-1 and bah-2 mutants have slightly fragile cuticles but are neither Srf nor Bus, suggesting that they are specific for surface components involved in biofilm attachment. A bah-3 mutant has normal cuticle integrity, but shows a stage-specific Srf phenotype. The screen produced alleles of five known surface genes: srf-2, srf-3, bus-4, bus-12, and bus-17. For the X-linked bus-17, a paternal effect was observed in biofilm assays.

Capsule does not block antibody binding to PspA, a surface virulence protein of Streptococcus pneumoniae.

Of the proteins on the surface of Streptococcus pneumoniae, one of those best able to elicit protection against pneumococcal infection is pneumococcal surface protein A (PspA). Although this protein is attached to the membrane molecule, lipoteichoic acid, which is well beneath the capsule, PspA's ability to inhibit complement deposition and killing by apolactoferrin, suggests that it must have surface exposure. This study provides quantitative data showing that the capsular polysaccharide on types 2 and 3 pneumococci provides little or no masking ability of antibodies to bind PspA. Capsule was even observed to enhance, rather than inhibit the binding of two protective monoclonal antibodies to their epitopes on cell surface PspA. These results with antibodies to PspA are in contrast to binding by antibodies to the phosphocholine (PC) epitope of the lipoteichoic and teichoic acids. The binding of antibody to PC was largely, but not completely, blocked by capsular polysaccharide.