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Pharmacogenomics promises improved outcomes through individualized prescribing. However, the lack of diversity in studies impedes clinical translation and equitable application of precision medicine. We evaluated the frequencies of PGx variants, predicted phenotypes, and medication exposures using whole genome sequencing and EHR data from nearly 100k diverse All of Us Research Program participants. We report 100% of participants carried at least one pharmacogenomics variant and nearly all (99.13%) had a predicted phenotype with prescribing recommendations. Clinical impact was high with over 20% having both an actionable phenotype and a prior exposure to an impacted medication with pharmacogenomic prescribing guidance. Importantly, we also report hundreds of alleles and predicted phenotypes that deviate from known frequencies and/or were previously unreported, including within admixed American and African ancestry groups.
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OBJECTIVE: Beta-lactam antibiotic allergies are reported in 5%-10% of children; however, up to 90% do not have any reaction at oral challenge test (OCT). This study aimed to determine the frequency and identify predictors of positive in-hospital graded beta-lactam OCTs in children with a beta-lactam antibiotic allergy label (AAL). DESIGN: This is a retrospective study conducted over 7 years, including children aged 0-19 years who underwent a beta-lactam OCT. The OCT comprised an in-hospital graded challenge followed by a 5-day outpatient antibiotic course. Univariate and multivariate logistic regression analyses were performed to identify predictors of a positive in-hospital graded OCT. RESULTS: Overall, 1259 beta-lactam OCTs were included: median age at time of OCT was 6.3 years (range 8.8 months to 19.2 years). Of these, 18 (1.4%) in-hospital graded OCTs were positive and 10 (0.8%) were equivocal, with only 4 children (0.3%) having an immediate, severe reaction to their in-hospital graded OCT. Factors associated with a positive in-hospital graded OCT on univariate analysis were: history of other drug allergy (OR 2.7, 95% CI 1.0 to 7.2; p 0.05), an index reaction which was severe (OR 2.9, 95% CI 1.1 to 7.6; p 0.035), immediate and severe (OR 5.85, 95% CI 1.7 to 20.0; p 0.005) or that required epinephrine (OR 9.65, 95% CI 1.7 to 53.6; p 0.01). CONCLUSION: Of the children referred with a beta-lactam AAL, only 1.4% had a positive in-hospital graded OCT. Risk factors for a positive in-hospital graded OCT were history of other drug allergy, an index reaction which was severe, immediate and severe or required epinephrine.
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Purpose: Uncorrected refractive errors (REs) and amblyopia can lead to visual impairment with deleterious effects on quality of life and academic performance. Early detection and treatment by community vision care programs, such as the UCI EyeMobile for Children, can aid in addressing preventable vision loss. Methods: A total of 5074 children between the ages of 3 and 10 years were screened at 153 locations, including preschools, head start programs, and elementary schools within Orange County (OC), California (CA). Subsequently, 1024 children presented for comprehensive eye examinations. A retrospective analysis of all examined children was conducted, determining the frequency and severity of REs and amblyopia and the spectacle prescription rate by age. Propensity score matching analysis evaluated the effect of median household income on RE and amblyopia frequency. Results: Among those who failed initial screening and were subsequently examined, significant rates of REs and amblyopia were detected: myopia (24.4%), hyperopia (35.4%), astigmatism (71.8%), anisometropia (8.9%), amblyopia (7.0%), and amblyopia risk (14.4%). A majority (65.0%) of those examined received prescription spectacles from UCI EyeMobile, with around a third requiring a new or updated prescription. The frequency of REs and amblyopia and the spectacle prescription rate were uniform across OC congressional districts. Myopia and amblyopia risk was positively and negatively associated with household income, respectively. Conclusion: The UCI EyeMobile for Children serves as a vital vision care program, providing free vision screening, comprehensive eye examinations, and spectacles. A significant number of children required examination, and a high frequency of REs and amblyopia were detected in examined children, with subsequent provision of prescription spectacles to most children.
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PURPOSE: To analyze referral rates, patient demographics, referral indications, and the impact of socioeconomic factors on ocular health from the University of California Irvine (UCI) Eye Mobile for Children, particularly during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective chart review was performed on de-identified records of children examined on the UCI Eye Mobile. GraphPad Prism 10.0.0 and Python software were used for statistical analyses. RESULTS: In the academic years from 2018 to 2022, 3,619 children received comprehensive eye examinations on the UCI Eye Mobile. Among them, 76 were referred to a pediatric ophthalmologist. The majority of these children were Hispanic (72.6%, 54 of 74), followed by Asian (10.9%, 8 of 74). A significant proportion (82.9%, 63 of 76) attended school districts with median incomes below that of Orange County. Statistically significant differences were found in age (P = .001; pre-COVID: 3.98 ± 1.08 years vs COVID: 5.75 ± 2.92 years) and gender (P = .023; pre-COVID female: 31 of 41 vs COVID female: 15 of 32) between the pre-COVID and COVID years. Additionally, there were significant differences in the proportion of children with hyperopia with astigmatism between the pre-COVID and COVID years (P = .044; pre-COVID: 23 of 40 vs COVID: 12 of 35). The most common indications for ophthalmologist referrals were for strabismus evaluation/treatment (28.9%, 22 of 76), followed by abnormal cup-to-disc ratio (21.1%, 16 of 76). CONCLUSIONS: The study highlights the pivotal role of the UCI Eye Mobile for children in identifying ocular conditions needing referrals to subspecialty care. The majority of children needing these referrals attended schools in lower economic communities. Additionally, the COVID-19 pandemic appears to have influenced the demographic and clinical characteristics. [J Pediatr Ophthalmol Strabismus. 20XX:X(X):XXX-XXX.].
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Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities.
Subject(s)
Genetic Predisposition to Disease , Population Health , Humans , Black People , Genomics , Hispanic or Latino/genetics , United States/epidemiology , European People , African People , Black or African AmericanABSTRACT
OBJECTIVES: (1) Examine the feasibility of a community-based exercise intervention for persons with spinal cord injury and (2) compare the cardiorespiratory fitness, skeletal muscle strength, and psychosocial well-being of participants in the intervention group versus control group. DESIGN: Community-based pilot randomized controlled trial. Setting: Accessible community-based health and wellness center. Participants: Thirty-two sedentary community-dwelling adults with any level of spinal cord injury. Interventions: Participants were randomized to a 36-session/12-week community-based exercise program (intervention; EG) or to a 36-session/12-week physical activity education group (control; CG). Outcome measures: Primary outcome measures included cardiorespiratory fitness measured by a VO2peak test, a composite score of four upper extremity musculoskeletal strength 1-repetition maximum exercises, and feasibility measured by EG participants' adherence and exercise intensity achieved during the program. EG participants' acceptance of the program was also evaluated using a self-reported satisfaction scale. Self-efficacy, motivation, pain, and goal performance and satisfaction were secondary outcome measures. Adherence and acceptability were also measured. RESULTS: Fifteen participants (n = 15) completed the community-based exercise intervention and seventeen (n = 17) completed the education program. While no statistically significant differences were found, the EG experienced changes of moderate effect size in cardiorespiratory fitness, strength, motivation, and satisfaction with their goals. The EG attended, on average, two sessions per week. The community-based exercise intervention was highly accepted by and satisfying for participants to engage in. CONCLUSIONS: The EG had improvements in the two primary measures, cardiorespiratory fitness and musculoskeletal strength, following the intervention. The community-based exercise intervention was feasible and accepted by participants.
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To examine the effectiveness of Mind Over Matter (MOM), a group psychosocial intervention based on CBT, ACT, and mind-body interventions, from data collected during a quality improvement project. MOM was offered in person prior to COVID-19 and via telehealth after COVID-19 began.Distress, as measured by anxiety, depression, the severity of physical symptoms and the impact of physical symptoms on daily functioning, was measured pre- and post-MOM.The sample included 46 participants with an experience of cancer ranging in age from 31 to 75.Overall, there were significant differences in anxiety, depression, and physical symptom severity and interference pre and post MOM. The in-person intervention showed significant differences in anxiety, depression, and physical symptom interference. There were significant differences in anxiety and physical symptom severity reported in the telehealth groups.MOM may be an effective psychosocial intervention for addressing cancer-related physical and emotional challenges making it a valuable resource for institutions trying to meet needs identified by distress screenings.
Subject(s)
COVID-19 , Neoplasms , Humans , Coping Skills , Quality of Life , Quality Improvement , Neoplasms/therapy , Anxiety/therapy , Depression/therapyABSTRACT
BACKGROUND: This study aimed to test, in real-world clinical practice, the effectiveness of a Transitional Care Stroke Intervention (TCSI) compared to usual care on health outcomes, self-management, patient experience, and health and social service use costs in older adults (≥ 55 years) with stroke and multimorbidity (≥ 2 chronic conditions). METHODS: This pragmatic randomized controlled trial (RCT) included older adults discharged from hospital to community with stroke and multimorbidity using outpatient stroke rehabilitation services in two communities in Ontario, Canada. Participants were randomized 1:1 to usual care (control group) or usual care plus the 6-month TCSI (intervention group). The TCSI was delivered virtually by an interprofessional (IP) team, and included care coordination/system navigation support, phone/video visits, monthly IP team conferences, and an online resource to support system navigation. The primary outcome was risk of hospital readmission (all cause) after six-months. Secondary outcomes included physical and mental functioning, stroke self-management, patient experience, and health and social service use costs. The intention-to-treat principle was used to conduct the primary and secondary analyses. RESULTS: Ninety participants were enrolled (44 intervention, 46 control); 11 (12%) participants were lost to follow-up, leaving 79 (39 intervention, 40 control). No significant between-group differences were seen for baseline to six-month risk of hospital readmission. Differences favouring the intervention group were seen in the following secondary outcomes: physical functioning (SF-12 PCS mean difference: 5.10; 95% CI: 1.58-8.62, p = 0.005), stroke self-management (Southampton Stroke Self-Management Questionnaire mean difference: 6.00; 95% CI: 0.51-11.50, p = 0.03), and patient experience (Person-Centred Coordinated Care Experiences Questionnaire mean difference: 2.64, 95% CI: 0.81, 4.47, p = 0.005). No between-group differences were found in total healthcare costs or other secondary outcomes. CONCLUSIONS: Although participation in the TCSI did not impact hospital readmissions, there were improvements in physical functioning, stroke self-management and patient experience in older adults with stroke and multimorbidity without increasing total healthcare costs. Challenges associated with the COVID-19 pandemic, including the shift from in-person to virtual delivery, and re-deployment of interventionists could have influenced the results. A larger pragmatic RCT is needed to determine intervention effectiveness in diverse geographic settings and ethno-cultural populations and examine intervention scalability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04278794 . Registered May 2, 2020.
Subject(s)
Stroke , Transitional Care , Aged , Humans , Multimorbidity , Ontario/epidemiology , Quality of Life , Stroke/diagnosis , Stroke/epidemiology , Stroke/therapyABSTRACT
Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Materials and Methods: Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0-1 considered to have excellent response and grades of 2-3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Results: Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Conclusion: Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT.
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Due to multi-drug resistance, physicians increasingly use the last-resort antibiotic colistin to treat infections with the Gram-negative bacterium Klebsiella pneumoniae. Unfortunately, K. pneumoniae can also develop colistin resistance. Interestingly, colistin resistance has dual effects on bacterial clearance by the immune system. While it increases resistance to antimicrobial peptides, colistin resistance has been reported to sensitize certain bacteria for killing by human serum. Here we investigate the mechanisms underlying this increased serum sensitivity, focusing on human complement which kills Gram-negatives via membrane attack complex (MAC) pores. Using in vitro evolved colistin resistant strains and a fluorescent MAC-mediated permeabilization assay, we showed that two of the three tested colistin resistant strains, Kp209_CSTR and Kp257_CSTR, were sensitized to MAC. Transcriptomic and mechanistic analyses focusing on Kp209_CSTR revealed that a mutation in the phoQ gene locked PhoQ in an active state, making Kp209_CSTR colistin resistant and MAC sensitive. Detailed immunological assays showed that complement activation on Kp209_CSTR in human serum required specific IgM antibodies that bound Kp209_CSTR but did not recognize the wild-type strain. Together, our results show that developing colistin resistance affected recognition of Kp209_CSTR and its killing by the immune system.
Subject(s)
Colistin , Klebsiella Infections , Humans , Colistin/pharmacology , Colistin/therapeutic use , Klebsiella pneumoniae/genetics , Bacterial Proteins/pharmacology , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Mutation , Immunoglobulin M/genetics , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Microbial Sensitivity TestsABSTRACT
SIGNIFICANCE: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study. PURPOSE: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia. METHODS: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism). RESULTS: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion). CONCLUSIONS: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial.
Subject(s)
Exotropia , Child , Humans , Child, Preschool , Exotropia/therapy , Eyeglasses , Pilot Projects , Refraction, Ocular , Vision TestsABSTRACT
Klebsiella pneumoniae is a leading cause of nosocomial infections, including pneumonia, bacteremia, and urinary tract infections. Treatment options are increasingly restricted by the high prevalence of resistance to frontline antibiotics, including carbapenems, and the recently identified plasmid-conferred colistin resistance. The classical pathotype (cKp) is responsible for most of the nosocomial infections observed globally, and these isolates are often multidrug resistant. The hypervirulent pathotype (hvKp) is a primary pathogen capable of causing community-acquired infections in immunocompetent hosts. The hypermucoviscosity (HMV) phenotype is strongly associated with the increased virulence of hvKp isolates. Recent studies demonstrated that HMV requires capsule (CPS) synthesis and the small protein RmpD but is not dependent on the increased amount of capsule associated with hvKp. Here, we identified the structure of the capsular and extracellular polysaccharide isolated from hvKp strain KPPR1S (serotype K2) with and without RmpD. We found that the polymer repeat unit structure is the same in both strains and that it is identical to the K2 capsule. However, the chain length of CPS produced by strains expressing rmpD demonstrates more uniform length. This property was reconstituted in CPS from Escherichia coli isolates that possess the same CPS biosynthesis pathway as K. pneumoniae but naturally lack rmpD. Furthermore, we demonstrate that RmpD binds Wzc, a conserved capsule biosynthesis protein required for CPS polymerization and export. Based on these observations, we present a model for how the interaction of RmpD with Wzc could impact CPS chain length and HMV. IMPORTANCE Infections caused by Klebsiella pneumoniae continue to be a global public health threat; the treatment of these infections is complicated by the high frequency of multidrug resistance. K. pneumoniae produces a polysaccharide capsule required for virulence. Hypervirulent isolates also have a hypermucoviscous (HMV) phenotype that increases virulence, and we recently demonstrated that a horizontally acquired gene, rmpD, is required for HMV and hypervirulence but that the identity of the polymeric product(s) in HMV isolates is uncertain. Here, we demonstrate that RmpD regulates capsule chain length and interacts with Wzc, a part of the capsule polymerization and export machinery shared by many pathogens. We further show that RmpD confers HMV and regulates capsule chain length in a heterologous host (E. coli). As Wzc is a conserved protein found in many pathogens, it is possible that RmpD-mediated HMV and increased virulence may not be restricted to K. pneumoniae.
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Cross Infection , Klebsiella Infections , Humans , Escherichia coli , Virulence/genetics , Virulence Factors/genetics , Klebsiella pneumoniae , Anti-Bacterial Agents , Polysaccharides , Klebsiella Infections/epidemiologyABSTRACT
State vaccine requirements are a tool for improving child and adolescent vaccination immunization coverage, but to be effective, parental buy-in is needed. The objective of this study was to assess the demographic, healthcare characteristics, and health beliefs associated with parental acceptance of general and HPV-specific state vaccine requirements. Indiana parents (N = 601) with children ages 11-17 years old completed a survey during March 2020.Results showed that 47.2% and 43.1% of parents believed there should always be general and HPV-specific state vaccine requirements, respectively. In multivariable analysis, higher odds of parental support for general state vaccine requirements were associated with being unsure whether HPV-associated cancer is a problem in the participant's county and having higher perceived benefits of HPV vaccines. Lower odds were associated with private insurance, having less than a bachelor's degree, and having less confidence in vaccines. In comparison, parents had higher odds of agreeing with HPV-specific state vaccine requirements if they reported higher interpersonal altruism and higher perceived benefits of HPV vaccines; they had lower odds if they were non-Hispanic White. Findings indicate that while similar percentages of parents agreed with general and HPV-specific state vaccine requirements, there were different characteristics associated with acceptance of each. Results can inform the development of tailored interventions for improving parental support for general and HPV-specific state vaccine requirements.
Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Adolescent , Child , Humans , Papillomavirus Vaccines/therapeutic use , Indiana , Papillomavirus Infections/prevention & control , Patient Acceptance of Health Care , Health Knowledge, Attitudes, Practice , Parents , Vaccination , Surveys and QuestionnairesABSTRACT
Oropharyngeal cancer (OPC) has the highest incidence of any cancer caused by human papillomavirus (HPV). Oral health providers are urged to support the use of the HPV vaccine, which was approved by the US Food and Drug Administration for the prevention of OPC in 2020. This study evaluated the preferences of dental patients regarding 11 modalities for learning about HPV-related topics from their oral health providers. An online survey was administered to US adults aged 18 to 45 years (n = 285) to assess their communication modality preferences, prior experience discussing HPV with oral health providers, and demographic characteristics. Multiple items were combined to obtain preference scores for each modality. Preference scores were compared using 2 × 3 mixed analysis of variance. Age, sex, income, and HPV vaccination status were assessed as potential confounders. One-on-one discussions were the most preferred modality for learning about HPV-related topics; however, the preference scores differed based on whether the patient had prior HPV-related discussions with oral health providers (partial η2 = 0.054). Patients who had prior discussions showed a weaker preference for one-on-one discussions than did patients who had not had prior discussions. Oral health providers are called on to promote HPV vaccination, which will require increasing communication on this subject with patients. To assure greater acceptance of their recommendations, providers will need to match their communication styles to those desired by their patients. As part of a comprehensive HPV prevention strategy that includes administration of the vaccine, oral health providers should be educated on how to confidently discuss HPV-related issues with their patients.
Subject(s)
Oropharyngeal Neoplasms , Papillomavirus Infections , Papillomavirus Vaccines , Humans , Human Papillomavirus Viruses , Papillomavirus Infections/complications , Papillomavirus Infections/prevention & control , Vaccination , Communication , Papillomavirus Vaccines/therapeutic use , Health Knowledge, Attitudes, PracticeABSTRACT
In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.
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COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Genomics , SoftwareABSTRACT
Background: Since COVID-19 vaccines became broadly available to the adult population, sharp divergences in uptake have emerged along partisan lines. Researchers have indicated a polarized social media presence contributing to the spread of mis- or disinformation as being responsible for these growing partisan gaps in uptake. Objective: The major aim of this study was to investigate the role of influential actors in the context of the community structures and discourse related to COVID-19 vaccine conversations on Twitter that emerged prior to the vaccine rollout to the general population and discuss implications for vaccine promotion and policy. Methods: We collected tweets on COVID-19 between July 1, 2020, and July 31, 2020, a time when attitudes toward the vaccines were forming but before the vaccines were widely available to the public. Using network analysis, we identified different naturally emerging Twitter communities based on their internal information sharing. A PageRank algorithm was used to quantitively measure the level of "influentialness" of Twitter accounts and identifying the "influencers," followed by coding them into different actor categories. Inductive coding was conducted to describe discourses shared in each of the 7 communities. Results: Twitter vaccine conversations were highly polarized, with different actors occupying separate "clusters." The antivaccine cluster was the most densely connected group. Among the 100 most influential actors, medical experts were outnumbered both by partisan actors and by activist vaccine skeptics or conspiracy theorists. Scientists and medical actors were largely absent from the conservative network, and antivaccine sentiment was especially salient among actors on the political right. Conversations related to COVID-19 vaccines were highly polarized along partisan lines, with "trust" in vaccines being manipulated to the political advantage of partisan actors. Conclusions: These findings are informative for designing improved vaccine information communication strategies to be delivered on social media especially by incorporating influential actors. Although polarization and echo chamber effect are not new in political conversations in social media, it was concerning to observe these in health conversations on COVID-19 vaccines during the vaccine development process.
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In this critical ethnographic study, we examined women's end of life experiences in Malawi, one of the few countries in the world with a national palliative care policy. Specifically, we explored how women's and their caregivers' experiences were shaped by family and community care, and material needs. Interviews and observations with female clients of a non-governmental organization in rural Central Malawi, and with their caregivers, revealed that community-level support was both precarious and critical. We found three main themes: (1) I stay with them well, (2) we eat together, and (3) everyone is for themselves. The analysis illustrates the centrality of community care, social in/exclusion, and availability of stable food, shelter, medical, and caregiving resources on health and wellbeing at end of life. We provide recommendations to strengthen community care opportunities and women's resource bases.
Subject(s)
Rural Population , Women's Health , Death , Female , Humans , Malawi , Palliative CareABSTRACT
PURPOSE: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping. METHODS: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record. RESULTS: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping. CONCLUSION: Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources.
Subject(s)
Cytochrome P-450 CYP2D6 , Pharmacogenetics , Academic Medical Centers , Base Sequence , Cytochrome P-450 CYP2D6/genetics , Genotype , Humans , Pharmacogenetics/methodsABSTRACT
BACKGROUND: The All of Us Research Program (AoURP, "the program") is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the USA. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants. METHODS: Whole-genome sequencing (WGS), variant calling processes, data interpretation, and return-of-results procedures had to be created and receive an Investigational Device Exemption (IDE) from the United States Food and Drug Administration (FDA). The performance of the entire workflow was assessed through the largest known cross-center, WGS-based, validation activity that was refined iteratively through interactions with the FDA over many months. RESULTS: The accuracy and precision of the WGS process as a device for the return of certain health-related genomic results was determined to be sufficient, and an IDE was granted. CONCLUSIONS: We present here both the process of navigating the IDE application process with the FDA and the results of the validation study as a guide to future projects which may need to follow a similar path. Changes to the program in the future will be covered in supplementary submissions to the IDE and will support additional variant classes, sample types, and any expansion to the reportable regions.