Parental understanding and attitudes following pharmacogenomic testing for pediatric neuropsychiatric patients.

Aim: This study explores parental understanding and attitudes around pharmacogenomic results in their child(ren). Patients and methods: In-depth interviews with parents whose child(ren) had received a pharmacogenomic testing panel for management of neuropsychiatric medications were completed. Interviews were analyzed for themes and accuracy of understanding of results. Results: In 18 parents interviewed, 49/63 (78%) of statements made regarding results were accurate. Differences in understanding were seen by clinic, number of medications and result type. Parents expected results to guide prescribing and perceived the greatest utility in results that could impact current care. Results predicting normal drug metabolism may create mixed feelings. Conclusion: Parents perceive utility in pharmacogenomic testing for their children. Challenges exist in understanding probabilistic and multifactorial information about pharmacogenomic results.

Retrospective Review of Pharmacogenetic Testing at an Academic Children's Hospital.

There is limited evidence to support pharmacogenetic (PGx) testing in children. We conducted a retrospective review of PGx testing among 452 patients at an academic children's hospital to determine the potential utility of PGx in diseases of childhood and to identify targets for future pediatric pharmacogenetic research. An actionable gene-drug pair associated with the 28 genes tested (Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B, Pharmacogenomics Knowledge Base (PharmGKB) level 1A or B, or US Food and Drug Administration (FDA) recommendation and a PharmGKB level) was present in 98.7% of patients. We identified 203 actionable gene-drug-diagnosis groups based on the indications for each actionable drug listed in Lexicomp. Among patients with an actionable gene-drug-diagnosis group, 49.3% had a diagnosis where the drug was a therapeutic option and PGx could be used to guide treatment selection. Among patients with an associated diagnosis, 30.9% had a prescription for the actionable drug allowing PGx guided dosing. Three genes (CYP2C19, CYP2D6, and CYP3A5) accounted for all the gene-drug-diagnosis groups with matching diagnoses and prescriptions. The most common gene-drug-diagnosis groups with matching diagnoses and prescriptions were CYP2C19-citalopram-escitalopram-depression 3.3% of patients tested; CYP2C19-dexlansoprazole-gastritis-esophagitis 3.1%; CYP2C19-omeprazole-gastritis-esophagitis 2.4%; CYP2D6-atomoxetine-attention deficit hyperactivity disorder 2.2%; and CYP2C19-citalopram-escitalopram-obsessive-compulsive disorder 1.5%. PGx could be used to guide selection of current treatment options or medication dosing in almost half (48.7%) of pediatric patients tested. Mood disorders and gastritis/esophagitis are promising targets for future study of PGx testing because of the high prevalence of these diagnoses and associated actionable gene-drug pairs in the pediatric population.

Operating room air delivery design to protect patient and surgical site results in particles released at surgical table having greater concentration along walls of the room than at the instrument tray.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, recommendations have included that personnel not involved in procedures releasing airborne contaminants reduce their exposure by moving >2 m away. We tested whether air particle concentrations in operating rooms (ORs) are greater in the periphery, downstream from the supply airflow. METHODS: We analyzed data from 15 mock surgical procedures performed in 3 ORs. Two ORs were modern, one with a single large diffuser system above the surgical table, and the other using a multiple diffuser array design. An air particle counting unit was located on the instrument table, another adjacent to an air return grille. RESULTS: Concentrations of air particles were greater at return grille than instrument table for the single large diffuser at 26 air exchanges per hour, and the multiple diffuser array at both 26 and 20 air exchanges per hour (all P ≤ .0044), including during electrocautery (all P ≤ .0072). The ratios of concentrations, return grille versus instrument table, were greater during electrocautery for 0.5 to 1.0-micron particles and 1.0 to 5.0-micron particles (both P < .0001). CONCLUSIONS: Modern OR airflow systems are so effective at protecting the surgical field and team from airborne particles emitted during surgery that concentrations of particles released at the OR table are greater at the OR walls than near the center of the room.

Examining a New Scale for Evaluating Taste in Children (TASTY).

OBJECTIVES: Pediatric medication taste impacts adherence, and current recommendations advocate for direct input from pediatric patients on medication taste during drug development. However, the lack of a widely used, validated measurement tool limits taste assessments. This protocol examines the validity of, and preferences for, a newly created self-report taste rating scale designed with images centered on taste (TASTY), compared with 2 existing hedonic taste scales. METHODS: This study was a prospective, single-center, randomized survey of child-parent dyads recruited from pediatric ambulatory care clinics and ancillary service waiting rooms. Parents facilitated the survey by identifying foods that they perceived their child would recall as pleasant, neutral, and unpleasant. Children were asked to rate each of the 3 food items on each of 3 different faces scales presented in random order. Parents and children were also asked which scale they preferred and why. RESULTS: Ninety child-parent dyads completed this study (mean child age was 6.7 ± 2.9 years, 58% female). All 3 scales performed comparably with no significant differences (p > 0.05). However, concordance between parental assignment and child rankings was markedly lower in 3-year-olds (r < 0.4) and 4-year-olds (r < 0.6) than for children 5 years and older (r > 0.9). TASTY was preferred by both parents and children when compared with the other scales. CONCLUSIONS: This novel hedonic taste scale for pediatric use is equally valid and preferred to comparable faces scales. The TASTY scale may be beneficial in developing standardized methodology for evaluating drug palatability.

Medicine and Media: The Ranitidine Debate.

Ranitidine has been the topic of recent media reports. Current findings, confirmed by the US Food and Drug Administration, indicate that some ranitidine products contain a substance that may be carcinogenic. Providers and patients require additional information on the risks of continuing therapy vs. the benefits of the medication. This article comments on what is currently known about the evolving situation of elevated N-nitrosodimethylamine levels in ranitidine and the limits of the existing information to assess best practices.

Analyzing ICU Patient Room Environmental Quality Through Unoccupied, Normal, and Emergency Procedure Modes: An EQI Evaluation.

BACKGROUND: There is increasing need to perform invasive surgical procedures in intensive care units (ICUs). Traditional ICUs differ from operating rooms (ORs) in several ways including air changes per hour (ACH) and pressurization. Increased ACH and positive pressurization of ORs intend to provide more aseptic environments for surgery. Development of procedure ready ICUs that transition through unoccupied, occupied, and procedure modes is one solution to improve environmental quality when performing surgery in ICUs. This study assessed the efficacy of two airflow control systems, variable air volume (VAV) and Venturi control, in preventing contaminants from entering ICU from adjacent corridors. STUDY DESIGN: Controlled contaminants, sulfur hexafluoride (SF6) and baker's yeast (CFU/m3), were released in the corridor adjacent to the ICU. SF6 and CFU/m3 were detected inside the ICU at the patient bed during a dynamic simulation of code blue event. VAV and Venturi were compared as they cycled the room through unoccupied, occupied, and procedure modes. RESULTS: VAV and Venturi showed significantly fewer CFU/m3 at the patient bed than corridor point of release (p < .05). Although not significant, Venturi cultured 14% fewer CFU/m3 than VAV at the patient bed. There was less SF6 detected at the patient bed with VAV and Venturi (p < .05). There was less SF6 detected at the patient bed with Venturi compared to VAV (p < .05). Venturi transitioned between modes faster than VAV (p < .05). CONCLUSION: Using efficient mode transitioning systems in ICUs may be effective in creating a more aseptic environment that mimics that of the OR.

Description of an Innovative Pediatric Individualized Therapeutics Clinic: Working toward Precision Drug Therapy.

The GOLDILOKs® (Genomic and Ontogeny-Linked Dose Individualization and cLinical Optimization for KidS) Clinic aims to provide families and physicians with data to make more informed decisions with regard to pharmacological therapy by using innovative therapy and genomic technologies. The objectives are two-fold: (1) To describe the utility of the GOLDILOKs® Clinic to referring prescribers by evaluating the type of referrals made to the GOLDILOKs® Clinic and (2) to assess the most often utilized technologies (e.g., genotyping) completed to formulate therapy recommendations. Patient data from July 2010 to June 2016 was retrospectively reviewed following Institutional Review Board (IRB) approval. The GOLDILOKs® Clinic evaluated 306 patients and had increases in annual referrals from 14 in 2010⁻2011 to 84 in 2016⁻2017. The children that were referred were predominately Caucasian (82%) and male (59%) with an average age of 12.4 ± 5.9 years. Subspecialty versus primary care referrals accounted for 82% and 18% of referrals, respectively. Adverse drug reactions (n = 166) and poor medication response (n = 179) were the major reasons for referral. However, it must be noted that patients could have multiple reasons for referral. Pharmacogenetic results were extensively used to provide guidance for future therapy in patients with medication-related problems. Genotyping of drug metabolizing enzymes and drug target receptors was performed in 221 patients (72.2%). Recommendations were fully accepted by 63% and partially accepted by 22% of internal provider referrals.

Comparison of operating room air distribution systems using the environmental quality indicator method of dynamic simulated surgical procedures.

BACKGROUND: Ensuring aseptic airborne environments for sterile fields and back instrument tables in operating rooms (ORs) is crucial to reducing microbial and particle contamination during surgery. Configurations of in-ceiling air delivery mechanisms impact the effectiveness of the system at eliminating contamination in critical zones. METHODS: The environmental quality indicator method was used to assess airborne environments in ORs equipped with a single large diffuser (SLD), a multidiffuser array (MDA), or a 4-way throw diffuser during dynamic, simulated surgical procedures. Environmental quality indicators measured included particles, microbes, carbon dioxide, velocity, humidity, and temperature at 26 air changes per hour. RESULTS: SLD ORs performed better than MDA ORs and 4-way throw diffuser ORs at removing microbes and carbon dioxide from the sterile field (P < .05). SLD ORs had higher velocity and lower temperature over the sterile field than the other 2 ORs (P < .05). MDA ORs had lower total particle counts than the other ORs (P < .05). The sterile fields in all ORs were cleaner than the respective back instrument tables (P < .05). CONCLUSIONS: Air delivery systems that eliminate blockages to uniform airflow directly over sterile zones, such as boom mounts and access panels, and deliver unidirectional, downward flow of clean filtered air provided a cleaner airborne environment within the sterile field. Expansion of air delivery systems to include areas outside the sterile field, where other surgical aides reside, may further reduce contamination within critical zones.

Characterization of human genetics courses for nonbiology majors in U.S. colleges and universities.

We characterized college human genetics courses for nonscience majors (NSM) by 1) determining the number of U.S. institutions offering courses and the number of students taking them; and 2) surveying course instructors on course demographics, content, materials, and pedagogies. Between 2002 and 2004, an estimated 480 institutions of higher education (15.2%) offered a course: 8.4% of 1667 associate colleges, 16.1% of baccalaureate institutions, 25.3% of master's institutions, and 32.9% of doctoral institutions. This indicates a need to increase access to genetics education in 2-yr colleges. Based on instructor responses, approximately 32,000-37,000 students annually complete an NSM human genetics course out of approximately 1.9 million students earning a college degree each year (2.0%). Regarding course content, instructors consistently rated many concepts significantly higher in importance than the emphasis placed on those concepts in their courses. Although time could be a factor, instructors need guidance in the integration of the various concepts into their courses. Considering only 30.2% of the instructors were reportedly trained in genetics (another 25.4% in molecular and cellular biology) and the small fraction of students completing NSM human genetics courses, these results demonstrate the need for increasing the availability of these courses in undergraduate institutions of higher education, and particularly at 2-yr colleges.

Identification of bacteria using matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS or simply MALDI)1 has become ubiquitous in the identification and analysis of biomacromolecules. As a technique that allows for the molecular weight determination of otherwise nonvolatile molecules, MALDI has had a profound impact in the molecular biosciences, especially in the field of proteomics. MALDI analysis of whole organisms allows for the generation of a phenotypic profile or "molecular fingerprint;" once established, these fingerprints can be used for identification purposes.

The intramitochondrial dynamin-related GTPase, Mgm1p, is a component of a protein complex that mediates mitochondrial fusion.

A balance between fission and fusion events determines the morphology of mitochondria. In yeast, mitochondrial fission is regulated by the outer membrane-associated dynamin-related GTPase, Dnm1p. Mitochondrial fusion requires two integral outer membrane components, Fzo1p and Ugo1p. Interestingly, mutations in a second mitochondrial-associated dynamin-related GTPase, Mgm1p, produce similar phenotypes to fzo1 and ugo cells. Specifically, mutations in MGM1 cause mitochondrial fragmentation and a loss of mitochondrial DNA that are suppressed by abolishing DNM1-dependent fission. In contrast to fzo1ts mutants, blocking DNM1-dependent fission restores mitochondrial fusion in mgm1ts cells during mating. Here we show that blocking DNM1-dependent fission in Deltamgm1 cells fails to restore mitochondrial fusion during mating. To examine the role of Mgm1p in mitochondrial fusion, we looked for molecular interactions with known fusion components. Immunoprecipitation experiments revealed that Mgm1p is associated with both Ugo1p and Fzo1p in mitochondria, and that Ugo1p and Fzo1p also are associated with each other. In addition, genetic analysis of specific mgm1 alleles indicates that Mgm1p's GTPase and GTPase effector domains are required for its ability to promote mitochondrial fusion and that Mgm1p self-interacts, suggesting that it functions in fusion as a self-assembling GTPase. Mgm1p's localization within mitochondria has been controversial. Using protease protection and immuno-EM, we have shown previously that Mgm1p localizes to the intermembrane space, associated with the inner membrane. To further test our conclusions, we have used a novel method using the tobacco etch virus protease and confirm that Mgm1p is present in the intermembrane space compartment in vivo. Taken together, these data suggest a model where Mgm1p functions in fusion to remodel the inner membrane and to connect the inner membrane to the outer membrane via its interactions with Ugo1p and Fzo1p, thereby helping to coordinate the behavior of the four mitochondrial membranes during fusion.