Publications by authors named "P E Hall"

2,289 Publications

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CYP2D6 Genotype Predicts Tamoxifen Discontinuation and Drug Response: A Secondary Analyses of the KARISMA Trial.

Ann Oncol 2021 Jul 17. Epub 2021 Jul 17.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Guidelines are conflicting and have caused confusion regarding whether tamoxifen should be prescribed based on women's CYP2D6 genotypes. This study aims to investigate if CYP2D6 metabolizer status is associated with tamoxifen-related endocrine symptoms, tamoxifen discontinuation, and mammographic density change.

Patients And Methods: We used data from 1,440 healthy women who participated the KARISMA dose determination trial. Endocrine symptom was measured using a modified Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) questionnaire. Change in mammographic density was measured and used as a proxy for tamoxifen response. Participants were genotyped and categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers.

Results: The median endoxifen level per mg oral tamoxifen among poor, intermediate, normal and ultrarapid CYP2D6 metabolizers were 0.18 ng/ml, 0.38 ng/ml, 0.56 ng/ml and 0.67 ng/ml, respectively. Ultrarapid CYP2D6 metabolizers were more likely than other groups to report a clinically relevant change in cold sweats, hot flash, mood swings, being irritable, as well as the overall modified FACT-ES score, after taking tamoxifen. The 6-month tamoxifen discontinuation rates among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 25.7%, 23.6%, 28.6%, and 44.4%, respectively. Among those who continued and finished the 6-month tamoxifen intervention, the mean change in dense area among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were -0.8 cm2, -4.5 cm2, -4.1 cm2, and -8.0 cm2, respectively.

Conclusions: Poor CYP2D6 metabolizers are likely to experience an impaired response to tamoxifen, measured through mammographic density reduction. In contrast, ultrarapid CYP2D6 metabolizers are at risk for exaggerated response with pronounced adverse effects that may lead to treatment discontinuation.
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http://dx.doi.org/10.1016/j.annonc.2021.07.005DOI Listing
July 2021

Mitigating the Impact of Reemergence From a Pandemic on Healthcare.

Authors:
Patricia L Hall

Mil Med 2021 Jul 17. Epub 2021 Jul 17.

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA.

Healthcare workers have never faced a medical crisis that compares to the coronavirus disease-2019 pandemic. This modern-day pandemic fight draws parallels to a war. Because of these similarities, it would make sense that the experiences frontline providers have when transitioning to a normal healthcare routine would emulate experiences service members voice when reintegrating home from a battlefield. These common experiences include a unified mission, an exhausting, adrenaline-packed responsibility, and a celebrity-like status to the public. The pandemic response consumed healthcare with one united mission, but as we reemerge from the pandemic and restore other aspects of our healthcare system, multiple missions develop and compete. Returning to a common routine and regular status can manifest feelings of disappointment in healthcare workers' everyday lives and career choices and lead to a reexamination of priorities and professions. As an organization with a focus on high reliability, mitigating the harm to staff and delivery system may be our new priority. The risk of not facing this situation head on is a potential exodus of seasoned professionals contemplating their future and selecting other career paths, thus draining the current institutional knowledge and potentially deterring future generations from healthcare. Leaders in the healthcare industry need to take a proactive stance in addressing this reemergence. Integrated, proactive programming is needed utilizing evidence-based resiliency training from professional organizations such as the National Alliance on Mental Illness, the Department of Health and Human Services' Substance Abuse and Mental Health Services Administration, as well as the existing Department of Defense programs. The Veterans Affairs has the backbone to develop and offer these programs and make a positive difference with Employee Whole Health efforts. Organized, evidence-based programming such as second victim education, mindfulness, and other personal skill building could be key to improving the lifelong well-being of our caregivers.
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http://dx.doi.org/10.1093/milmed/usab265DOI Listing
July 2021

Examining the relationships among adolescent health behaviours, prefrontal function, and academic achievement using fNIRS.

Dev Cogn Neurosci 2021 Aug 1;50:100983. Epub 2021 Jul 1.

School of Public Health Sciences, University of Waterloo, Waterloo, ON, Canada; Department of Psychology, University of Waterloo, Waterloo, ON, Canada; Centre for Bioengineering and Biotechnology, University of Waterloo, Waterloo, Canada. Electronic address:

Several adolescent health behaviours have been hypothesized to improve academic performance via their beneficial impact on cognitive control and functional aspects of the prefrontal cortex (PFC). The primary objective of this study is to examine the association between lifestyle behaviours and academic performance in a sample of adolescents, and to examine the extent to which activity within the PFC and behavioural indices of inhibition may mediate this relationship. Sixty-seven adolescents underwent two study sessions five days apart. Sleep and physical activity were measured using wrist-mounted accelerometry; eating habits, substance use and academic achievement were measured by self-report. Prefrontal function was quantified by Multi-Source Interference Task (MSIT) performance, and task-related activity via functional near-infrared spectroscopy (fNIRS). Higher levels of physical activity predicted higher MSIT accuracy scores (β = .321, ρ = 0.019) as well as greater activation within the right dlPFC (b = .008, SE = .004, ρ = .0322). Frequency of fast-food consumption and substance use were negatively associated with MSIT accuracy scores (β = -0.307, ρ = .023) and Math grades (b = -3.702, SE = 1.563, ρ = .022), respectively. Overall, the results of this study highlight the importance of lifestyle behaviours as predictors of prefrontal function and academic achievement in youth.
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http://dx.doi.org/10.1016/j.dcn.2021.100983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280512PMC
August 2021

Quantitative Hemolysis Assays.

Methods Mol Biol 2021 ;2341:25-30

Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, KS, USA.

Many strains of Staphylococcus aureus produce a variety of cytolysins that target many different cell types to both fight the immune system and acquire nutrients. This includes hemolysins which destroy erythrocytes and are well studied virulence factors. Traditionally, hemolysin activity is measured on blood agar plates due to the simplicity of the assay. While this is telling, it cannot encapsulate the full story because S. aureus is known to behave differently in broth and on agar. Furthermore, plate-based assays are primarily semiquantitative and often a more accurate determination of hemolytic potential is needed to discern differences between strains. Here, we describe a method to quantify hemolysin activity from broth or similarly grown cells.
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http://dx.doi.org/10.1007/978-1-0716-1550-8_4DOI Listing
January 2021

The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses.

JIMD Rep 2021 Jul 5;60(1):67-74. Epub 2021 Apr 5.

Biochemical Genetics Laboratory, Mayo Clinic Rochester Minnesota USA.

Background: Glutaric acidemia type I (GA1) is an organic acidemia that is often unrecognized in the newborn period until patients suffer an acute encephalopathic crisis, which can be mistaken for nonaccidental trauma. Presymptomatic identification of GA1 patients is possible by newborn screening (NBS). However, the biochemical "low-excretor" (LE) phenotype with nearly normal levels of disease metabolites can be overlooked, which may result in untreated disease and irreversible neurological sequelae. The LE phenotype is also a potential source of false negative (FN) NBS results that merits further investigation.

Methods: Samples from six LE GA1 patients were analyzed by biochemical and molecular methods and newborn screen outcomes were retrospectively investigated.

Results: Five LE GA1 patients were identified that had normal NBS results and three of these presented clinically with GA1 symptoms. One additional symptomatic patient was identified who did not undergo screening. Semiquantitative urine organic acid analysis was consistent with a GA1 diagnosis in two (33%) of the six patients, while plasma glutarylcarnitine was elevated in four (67%) of the six and urine glutarylcarnitine was elevated in four (80%) of five patients. Five variants were identified in these patients; three of which have not been previously linked to the biochemical LE phenotype.

Conclusions: The data presented here raise awareness of potential FN NBS results for LE GA1 patients. The LE phenotype is not protective against adverse clinical outcomes, and the possibility of FN NBS results calls for high vigilance amongst clinicians, even in the setting of a normal NBS result.
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http://dx.doi.org/10.1002/jmd2.12217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260482PMC
July 2021