Now showing items 21-40 of 18390

    • Time-restricted Eating to Address Cancer-related Fatigue among Cancer Survivors: A Single-arm Pilot Study.

      Kleckner, Amber S; Altman, Brian J; Reschke, Jennifer E; Kleckner, Ian R; Culakova, Eva; Dunne, Richard F; Mustian, Karen M; Peppone, Luke J (2022-05-30)
      Purpose: Cancer-related fatigue is a prevalent, debilitating condition that can persist for months or years after treatment. In a single-arm clinical trial, the feasibility and safety of a time-restricted eating (TRE) intervention were evaluated among cancer survivors, and initial estimates of within-person change in cancer-related fatigue were obtained. Methods: Participants were 4-60 months post-cancer treatment, were experiencing fatigue (≥ 3 on a scale 0-10), and were not following TRE. TRE entailed limiting all food and beverages to a self-selected 10-h window for 14 days. Participants reported their eating window in a daily diary and completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Brief Fatigue Inventory (BFI), and symptom inventory pre- and post-intervention. This study was pre-registered at clinicaltrials.gov in January 2020 (NCT04243512). Results: Participants (n=39) were 61.5 ± 12.4 years old and 1.8 ± 1.3 years post-treatment; 89.7% had had breast cancer. The intervention was feasible in that 36/39 (92.3%) of participants completed all questionnaires and daily diaries. It was also safe with no severe adverse events or rapid weight loss (average loss of 1.1 ± 2.3 pounds, p=0.008). Most adhered to TRE; 86.1% ate within a 10-h window at least 80% of the days, and the average eating window was 9.33 ± 1.05 h. Fatigue scores improved 5.3 ± 8.1 points on the FACIT-F fatigue subscale (p<0.001, effect size [ES]=0.55), 30.6 ± 35.9 points for the FACIT-F total score (p<0.001, ES=0.50), and -1.0 ± 1.7 points on the BFI (p<0.001, ES=-0.58). Conclusion: A 10-h TRE intervention was feasible and safe among survivors, and fatigue improved with a moderate effect size after two weeks. Limitations: This was a single-arm study, so it is possible that expectation effects were present for fatigue outcomes, independent of effects of TRE per se. However, this feasibility trial supports evaluation of TRE in randomized controlled trials to address persistent cancer-related fatigue.
    • Retention of Minocycline Susceptibility When Gram-Positive Periprosthetic Joint Infection Isolates Are Non-Susceptible to Doxycycline.

      Doub, James B; Nandi, Sumon; Putnam, Nicole (2022-08-29)
      The treatment of hardware infections often utilizes chronic oral suppression antibiotics to prevent infection recurrence. However, when methicillin-resistant Staphylococcus aureus and other bacteria are non-susceptible to doxycycline, limited oral antibiotic options can be available that do not cause significant side effects and drug-drug interactions. Consequently, the purpose of this study was to evaluate the ability of Gram-positive clinical prosthetic joint infection isolates that were non-susceptible to doxycycline and to retain susceptibility to minocycline.
    • A Comparison of Dinoflagellate Thiolation Domain Binding Proteins Using In Vitro and Molecular Methods.

      Williams, Ernest; Bachvaroff, Tsvetan; Place, Allen (2022-09-18)
      Dinoflagellates play important roles in ecosystems as primary producers and consumers making natural products that can benefit or harm environmental and human health but are also potential therapeutics with unique chemistries. Annotations of dinoflagellate genes have been hampered by large genomes with many gene copies that reduce the reliability of transcriptomics, quantitative PCR, and targeted knockouts. This study aimed to functionally characterize dinoflagellate proteins by testing their interactions through in vitro assays. Specifically, nine Amphidinium carterae thiolation domains that scaffold natural product synthesis were substituted into an indigoidine synthesizing gene from the bacterium Streptomyces lavendulae and exposed to three A. carterae phosphopantetheinyl transferases that activate synthesis. Unsurprisingly, several of the dinoflagellate versions inhibited the ability to synthesize indigoidine despite being successfully phosphopantetheinated. However, all the transferases were able to phosphopantetheinate all the thiolation domains nearly equally, defying the canon that transferases participate in segregated processes via binding specificity. Moreover, two of the transferases were expressed during growth in alternating patterns while the final transferase was only observed as a breakdown product common to all three. The broad substrate recognition and compensatory expression shown here help explain why phosphopantetheinyl transferases are lost throughout dinoflagellate evolution without a loss in a biochemical process.
    • Lymphoepithelial Subtype of Oral Squamous Cell Carcinoma: Report of an EBV-Negative Case and Literature Review.

      Emfietzoglou, Rodopi; Pettas, Efstathios; Georgaki, Maria; Papadopoulou, Erofili; Theofilou, Vasileios Ionas; Papadogeorgakis, Nikolaos; Piperi, Evangelia; Lopes, Marcio Ajudarte; Nikitakis, Nikolaos G (2022-09-05)
      Lymphoepithelial carcinoma (LEC) of the oral mucosa is a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with nasopharyngeal carcinoma (NPC), non-keratinizing undifferentiated subtype. The admixture of neoplastic epithelial tumor cells and a dense lymphoplasmacytic infiltrate makes microscopic diagnosis challenging. LEC etiopathogenesis has been variably associated with Epstein–Barr virus (EBV) infection, depending on the specific anatomic location and racial predilection, with a higher incidence in endemic populations. Although described in several subsites of the head and neck region, including the major salivary glands, the oral mucosa is considered an infrequent location for LEC development, deriving either from minor salivary glands (MSGs) or the surface epithelium. Herein, we report a rare case of an EBV-negative LEC arising from the oral surface epithelium, presenting as gingival swelling, and review the pertinent English-language literature, which revealed only 26 previously reported oral LECs. Our case is only
    • Racial/Ethnic Identity as a Factor of Academic Resilience in Female Black and Hispanic Undergraduate College Students Attending a PWI

      Miremadi-Baldino, Delvina D.; Ward, Janie (2013-04-12)
      This research explores the gap between Black and White and Hispanic and White student degree attainment in predominately white institutions (PWI). The cost associated with each individual who fails to matriculate and attain their degree is significant for the individual, the institution and for society as a whole. The purpose of this study was to explore the risk and protective factors associated with the Black and Hispanic undergraduate experience, as well as the multiple ways in which students’ perceptions of their sense of racial/ethnic identity contribute to the specific protective mechanisms that buffer the effects of exposure to risk and foster students’ academic resiliency. For this study, phenomenology research methodology allowed Black and Hispanic students to describe their perceptions of the undergraduate college experience at a PWI. Data collection methods included in-depth, one-on-one, semi-structured, interviews with eleven undergraduate college students. Findings indicate that Black and Latina students experience a variety of risk and protective factors that can positively or negatively impact their identity, academic resilience and success as a student. Data results highlight the importance of a po sitive Racial/Ethnic Identity as an important protective factor for academic success. Analysis revealed that Isolation and a Lack of Sense of Belonging and Isolation, Racism and Microaggressions, and Financial Difficulties were among the most significant challenges faced by the students. The protective mechanisms of family, group and peer support, internal purpose and goals, and identity duality proved to be the most salient protective factors that contribute to student perseverance. This research revealed important insights associated with increasing positive college experiences for Black and Hispanic undergraduate students. Implications and recommendations for improving institutional commitments to these student populations will be highlighted and discussed.
    • Catheter-directed computed tomography angiography: A pictorial essay.

      Ghosh, Abheek; Moxley, Ellen; Waghmarae, Suneet; Stoner, James; Anand, Sheena; Akhter, Nabeel M (2022-08-18)
      Catheter-directed computed tomography angiography (CDCTA) is an imaging technique where CT images are acquired after selective catheterization of a vessel. Images obtained in this fashion provide several advantages over conventional imaging techniques such as fluoroscopic angiography, digital subtraction angiography, cone-beam CT, and conventional CT angiography. At this point, there is still limited literature on the subject, with prior studies examining a small number of potential uses. The goal of this pictorial essay is to illustrate our single tertiary care center experience using CDCTA.
    • Transradial versus transfemoral arterial access in DEB-TACE for hepatocellular carcinoma.

      Ghosh, Abheek; Gupta, Vikash; Al Khalifah, Abdullah; Akhter, Nabeel Mohsin (2022-07-15)
      Objectives: Transradial access has become increasingly popular in body interventional procedures but has not been ubiquitously adapted. This retrospective study compares the efficacy of this approach versus transfemoral access in hepatocellular carcinoma (HCC) patients who underwent drug-eluting bead transarterial chemoembolization (DEB-TACE). Materials and methods: A total of 130 HCC patients underwent 146 DEB-TACE procedures within our institution from June 2015 to May 2020. About 90 and 56 procedures were logged for the transradial and transfemoral cohorts, respectively. Peak skin dose, fluoroscopy time, administered contrast volume, total procedure time, and equipment cost data for each procedure were reviewed to evaluate for statistical differences between the two groups. Results: All 146 cases were technically successful without major complications or access failures in either group. No statistical differences were present between the two access groups in regards to peak skin dose or fluoroscopy time. Transradial access recorded a significantly higher contrast volume (P < 0.05), and a significantly longer procedural time than transfemoral access (P < 0.01). However, transradial access also displayed a significantly lower procedural equipment cost (P < 0.01) between the two groups. Conclusion: Transradial DEB-TACE has similar trends to transfemoral DEB-TACE in several pertinent radiation parameters and is also significantly more cost-efficacious. The results of this investigation suggest the consideration of transradial access whenever viable as an alternative to transfemoral access in the DEB-TACE treatment of HCC patients.
    • A Tale of 2 Wheels: When Too Much "Spinning" Can Get You in Trouble.

      Restrepo, Alejandro Jimenez (2022-09-07)
      Cycling is a worldwide passionately practiced and followed by millions of people across the globe. While many of us see it as an enjoyable leisure activity or a healthy way to commute to and from work, for some recreational cyclists it can become an obsession. Avid recreational cyclists oftentimes put their body through such rigorous and demanding training blocks in order to achieve peak levels of performance that they can reach workloads comparable to those endured by professional cyclists. Whether it is watching cycling pros battling fierce uphill inclines every summer at the Tour de France or trying to overtake a fellow cyclist on a local hill during a weekend Café ride, cycling enthusiasts live their sport with passion and an almost religious-like devotion.
    • Inactivation of the basolateral amygdala to insular cortex pathway makes sign-tracking sensitive to outcome devaluation.

      Keefer, Sara E; Kochli, Daniel E; Calu, Donna J (2022-09-20)
      Goal-tracking rats are sensitive to Pavlovian outcome devaluation while sign-tracking rats are devaluation insensitive. During outcome devaluation, goal-tracking (GT) rats flexibly modify responding to cues based on the current value of the associated outcome. However, sign-tracking (ST) rats rigidly respond to cues regardless of the current outcome value. Prior work demonstrated disconnection of the basolateral amygdala (BLA) and anterior insular cortex (aIC) decreased both goal- and sign-tracking behaviors. Given the role of these regions in appetitive motivation and behavioral flexibility we predicted that disrupting BLA to aIC pathway during outcome devaluation would reduce flexibility in GT rats and reduce rigid appetitive motivation in ST rats. We inhibited the BLA to aIC pathway by infusing inhibitory DREADDs (hM4Di-mcherry) or control (mCherry) virus into the BLA and implanted cannulae into the aIC to inhibit BLA terminals using intracranial injections of clozapine N-oxide (CNO). After training, we used a within-subject satiety-induced outcome devaluation procedure in which we sated rats on training pellets (devalued condition) or homecage chow (valued condition). All rats received bilateral CNO infusions into the aIC prior to brief non-reinforced test sessions. Contrary to our hypothesis, BLA-IC inhibition did not interfere with devaluation sensitivity in GT rats but did make ST behaviors sensitive to devaluation. Intermediate rats showed the opposite effect, showing rigid responding to cues with BLA-aIC pathway inactivation. Together, these results demonstrate BLA-IC projections mediate tracking-specific Pavlovian devaluation sensitivity and highlights the importance of considering individual differences in Pavlovian approach when evaluating circuitry contributions to behavioral flexibility.
    • Decreased PRESET-Score corresponds with improved survival in COVID-19 veno-venous extracorporeal membrane oxygenation.

      Powell, Elizabeth K; Lankford, Allison S; Ghneim, Mira; Rabin, Joseph; Haase, Daniel J; Dahi, Siamak; Deatrick, Kristopher B; Krause, Eric; Bittle, Gregory; Galvagno, Samuel M; et al. (2022-09-16)
      Introduction: The PREdiction of Survival on ECMO Therapy Score (PRESET-Score) predicts mortality while on veno-venous extracorporeal membrane oxygenation (VV ECMO) for acute respiratory distress syndrome. The aim of our study was to assess the association between PRESET-Score and survival in a large COVID-19 VV ECMO cohort. Methods: This was a single-center retrospective study of COVID-19 VV ECMO patients from 15 March 2020, to 30 November 2021. Univariable and Multivariable analyses were performed to assess patient survival and score differences. Results: A total of 105 patients were included in our analysis with a mean PRESET-Score of 6.74. Overall survival was 65.71%. The mean PRESET-Score was significantly lower in the survivor group (6.03 vs 8.11, p < 0.001). Patients with a PRESET-Score less than or equal to six had improved survival compared to those with a PRESET-Score greater than or equal to 8 (97.7% vs. 32.5%, p < 0.001). In a multivariable logistic regression, a lower PRESET-Score was also predictive of survival (OR 2.84, 95% CI 1.75, 4.63, p < 0.001). Conclusion: We demonstrate that lower PRESET scores are associated with improved survival. The utilization of this validated, quantifiable, and objective scoring system to help identify COVID-19 patients with the greatest potential to benefit from VV-ECMO appears feasible. The incorporation of the PRESET-Score into institutional ECMO candidacy guidelines can help insure and improve access of this limited healthcare resource to all critically ill patients.
    • Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial

      Afolabi, Bosede B.; Babah, Ochuwa A.; Akinajo, Opeyemi R.; Adaramoye, Victoria O.; Adeyemo, Titilope A.; Balogun, Mobolanle; Banke-Thomas, Aduragbemi; Quao, Rachel A.; Olorunfemi, Gbenga; Abioye, Ajibola I.; et al. (2022-09-08)
      BACKGROUND: Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa. The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose. METHODS: This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20-32 weeks' gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum. Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks' gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks' gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions. DISCUSSION: The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned.
    • Blunt splenic injury: Assessment of follow-up CT utility using quantitative volumetry.

      Dreizin, David; Yu, Theresa; Motley, Kaitlynn; Li, Guang; Morrison, Jonathan J; Liang, Yuanyuan (2022-07-22)
      Purpose: Trials of non-operative management (NOM) have become the standard of care for blunt splenic injury (BSI) in hemodynamically stable patients. However, there is a lack of consensus regarding the utility of follow-up CT exams and relevant CT features. The purpose of this study is to determine imaging predictors of splenectomy on follow-up CT using quantitative volumetric measurements. Methods: Adult patients who underwent a trial of non-operative management (NOM) with follow-up CT performed for BSI between 2017 and 2019 were included (n = 51). Six patients (12% of cohort) underwent splenectomy; 45 underwent successful splenic salvage. Voxelwise measurements of splenic laceration, hemoperitoneum, and subcapsular hematoma were derived from portal venous phase images of admission and follow-up scans using 3D slicer. Presence/absence of pseudoaneurysm on admission and follow-up CT was assessed using arterial phase images. Multivariable logistic regression was used to determine independent predictors of decision to perform splenectomy. Results: Factors significantly associated with splenectomy in bivariate analysis incorporated in multivariate logistic regression included final hemoperitoneum volume (p = 0.003), final subcapsular hematoma volume (p = 0.001), change in subcapsular hematoma volume between scans (p = 0.09) and new/persistent pseudoaneurysm (p = 0.003). Independent predictors of splenectomy in the logistic regression were final hemoperitoneum volume (unit OR = 1.43 for each 100 mL change; 95% CI: 0.99-2.06) and new/persistent pseudoaneurysm (OR = 160.3; 95% CI: 0.91-28315.3). The AUC of the model incorporating both variables was significantly higher than AAST grading (0.91 vs. 0.59, p = 0.025). Mean combined effective dose for admission and follow up CT scans was 37.4 mSv. Conclusion: Follow-up CT provides clinically valuable information regarding the decision to perform splenectomy in BSI patients managed non-operatively. Hemoperitoneum volume and new or persistent pseudoaneurysm at follow-up are independent predictors of splenectomy.
    • Dynamics of the Gut Microbiome in Shigella-Infected Children during the First Two Years of Life.

      Ndungo, Esther; Holm, Johanna B; Gama, Syze; Buchwald, Andrea G; Tennant, Sharon M; Laufer, Miriam K; Pasetti, Marcela F; Rasko, David A (2022-09-19)
      Shigella continues to be a major contributor to diarrheal illness and dysentery in children younger than 5 years of age in low- and middle-income countries. Strategies for the prevention of shigellosis have focused on enhancing adaptive immunity. The interaction between Shigella and intrinsic host factors, such as the microbiome, remains unknown. We hypothesized that Shigella infection would impact the developing microbial community in infancy and, conversely, that changes in the gastrointestinal microbiome may predispose infections. To test this hypothesis, we characterized the gastrointestinal microbiota in a longitudinal birth cohort from Malawi that was monitored for Shigella infection using 16S rRNA amplicon sequencing. Children with at least one Shigella quantitative polymerase chain reaction (qPCR) positive sample during the first 2 years of life (cases) were compared to uninfected controls that were matched for sex and age. Overall, the microbial species diversity, as measured by the Shannon diversity index, increased over time, regardless of case status. At early time points, the microbial community was dominated by Bifidobacterium longum and Escherichia/Shigella. A greater abundance of Prevotella 9 and Bifidobacterium kashiwanohense was observed at 2 years of age. While no single species was associated with susceptibility to Shigella infection, significant increases in Lachnospiraceae NK4A136 and Fusicatenibacter saccharivorans were observed following Shigella infection. Both taxa are in the family Lachnospiraceae, which are known short-chain fatty acid producers that may improve gut health. Our findings identified temporal changes in the gastrointestinal microbiota associated with Shigella infection in Malawian children and highlight the need to further elucidate the microbial communities associated with disease susceptibility and resolution. IMPORTANCE Shigella causes more than 180 million cases of diarrhea globally, mostly in children living in poor regions. Infection can lead to severe health impairments that reduce quality of life. There is increasing evidence that disruptions in the gut microbiome early in life can influence susceptibility to illnesses. A delayed or impaired reconstitution of the microbiota following infection can further impact overall health. Aiming to improve our understanding of the interaction between Shigella and the developing infant microbiome, we investigated changes in the gut microbiome of Shigella-infected and uninfected children over the course of their first 2 years of life. We identified species that may be involved in recovery from Shigella infection and in driving the microbiota back to homeostasis. These findings support future studies into the elucidation of the interaction between the microbiota and enteric pathogens in young children and into the identification of potential targets for prevention or treatment.
    • Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report.

      Uysal, Ilkay Başak; Boué, Vanina; Murall, Carmen Lia; Graf, Christelle; Selinger, Christian; Hirtz, Christophe; Bernat, Claire; Ravel, Jacques; Reynes, Jacques; Bonneau, Marine; et al. (2022-08-19)
      Human papillomaviruses (HPVs), the most oncogenic virus known to humans, are often associated with Herpes Simplex Virus-2 (HSV-2) infections. The involvement of the latter in cervical cancer is controversial but its long-term infections might modulate the mucosal microenvironment in a way that favors carcinogenesis. We know little about coinfections between HSV-2 and HPVs, and studying the immunological and microbiological dynamics in the early stages of these infections may help identify or rule out potential interactions. We report two cases of concomitant productive, although asymptomatic, HSV-2 and HPV infections in young women (aged 20 and 25). The women were followed up for approximately a year, with clinical visits every two months and weekly self-samples. We performed quantitative analyses of their HSV-2 and HPV viral loads, immunological responses (IgG and IgM antibodies and local cytokines expression profiles), vaginal microbiota composition, as well as demographic and behavior data. We detect interactions between virus loads, immune response, and the vaginal microbiota, which improve our understanding of HSV-2 and HPVs' coinfections and calls for further investigation with larger cohorts.
    • Preferences for Treatments for Major Depressive Disorder: Formative Qualitative Research Using the Patient Experience.

      dosReis, Susan; Bozzi, Laura M; Butler, Beverly; Xie, Richard Z; Chapman, Richard H; Bright, Jennifer; Malik, Erica; Slejko, Julia F (2022-09-19)
      Objectives: The goals of this formative research are to elicit attributes of treatment and desired outcomes that are important to individuals with major depressive disorder (MDD), to develop a stated preference instrument, and to pre-test the instrument. Methods: A three-phase survey study design elicited the patient's journey with MDD to design and pre-test the discrete choice experiment (DCE) instrument. Participants were 20 adults aged ≥ 18 with MDD who did not also have bipolar disorder or post-partum depression. We engaged patient advocates and a multi-disciplinary stakeholder advisory group to select and refine attributes for inclusion in a DCE instrument. The DCE was incorporated into a survey that also collected depression treatment and management and sociodemographic characteristics. The DCE was pre-tested with ten adults with MDD. Results: Six attributes were included in the DCE: mode of treatment (medicine only, psychotherapy only, all modalities including brain stimulation), time to treatment effect (6, 9, 12 weeks), days of hopefulness (2, 4, 6 days/week), effect on productivity (40%, 60%, 90% increase), relations with others (strained, improved, no impact), and out-of-pocket costs ($30, $60, $90/month). The DCE test led to the refinement of mode of treatment (medicine, medicine and psychotherapy, and all modalities); time to treatment effect (4, 6, 9 weeks); monthly out-of-pocket costs ($30, $90, $270). Conclusions: MDD treatment preferences revealed trade-offs among mode of treatment, time to treatment effect, functional outcomes, and cost. The findings demonstrate the potential for meaningfully incorporating the patient experience in preference measures.
    • Vaccine-induced seroconversion in participants in the North Carolina COVID-19 community Research Partnership.

      Friedman-Klabanoff, DeAnna J; Tjaden, Ashley H; Santacatterina, Michele; Munawar, Iqra; Sanders, John W; Herrington, David M; Wierzba, Thomas F; Berry, Andrea A (2022-09-12)
      Well-regulated clinical trials have shown FDA-approved COVID-19 vaccines to be immunogenic and highly efficacious. We evaluated seroconversion rates in adults reporting ≥ 1 dose of an mRNA COVID-19 vaccine in a cohort study of nearly 8000 adults residing in North Carolina to validate immunogenicity using a novel approach: at-home, participant administered point-of-care testing. Overall, 91.4% had documented seroconversion within 75 days of first vaccination (median: 31 days). Participants who were older and male participants were less likely to seroconvert (adults aged 41-65: adjusted hazard ratio [aHR] 0.69 [95% confidence interval (CI): 0.64, 0.73], adults aged 66-95: aHR 0.55 [95% CI: 0.50, 0.60], compared to those 18-40; males: aHR 0.92 [95% CI: 0.87, 0.98], compared to females). Participants with evidence of prior infection were more likely to seroconvert than those without (aHR 1.50 [95% CI: 1.19, 1.88]) and those receiving BNT162b2 were less likely to seroconvert compared to those receiving mRNA-1273 (aHR 0.84 [95% CI: 0.79, 0.90]). Reporting at least one new symptom after first vaccination did not affect time to seroconversion, but participants reporting at least one new symptom after second vaccination were more likely to seroconvert (aHR 1.11 [95% CI: 1.05, 1.17]). This data demonstrates the high community-level immunogenicity of COVID-19 vaccines, albeit with notable differences in older adults, and feasibility of using at-home, participant administered point-of-care testing for community cohort monitoring.
    • An assessment of physician assistant student diversity in the United States: a snapshot for the healthcare workforce.

      Bradley-Guidry, Carolyn; Burwell, Nicole; Dorough, Ramona; Bester, Vanessa; Kayingo, Gerald; Suzuki, Sumihiro (2022-09-15)
      Background: The Physician Assistant (PA) workforce falls short of mirroring national demographics mainly due to a lack of diversity in student enrollment. Few studies have systematically examined diversity across PA programs at the national level, and little is known about best practices for consistently graduating a diverse group of students. We descriptively characterized the extent to which PA programs are graduating a diverse group of students and identified top performing PA programs. Methods: Data from the Integrated Postsecondary Education Data System (IPEDS) were used to calculate the number and proportion of racial or ethnically diverse graduates. The study sample included 139 accredited PA programs that had graduated a minimum of five cohorts from 2014-2018. Within each of the United States Census Divisions, programs were ranked according to the number and proportion of graduates who were underrepresented minority (URM) race, Hispanic ethnicity, and of non-white (URM race, Hispanic, and Asian). Results: Amongst PA programs in the United States, a large disparity in the number and proportion of racial and ethnic graduates was observed. Of 34,625 PA graduates, only 2,207 (6.4%) were Hispanic ethnicity and 1,220 (3.5%) were URM race. Furthermore, a large number of diverse graduates came from a small number of top performing programs. Conclusion: Despite the abundance of evidence for the need to diversify the healthcare workforce, PA programs have had difficulty recruiting and graduating a diverse group of students. This study provides empirical evidence that PA programs have not been able to attain the level of diversity necessary to shift the lack of diversity in the PA workforce. Based upon this study's findings, the top performing PA programs can be used as role models to establish benchmarks for other programs. The results of this descriptive study are currently being used to guide a qualitative study to identify the top performers' strategies for success.
    • Estimating deaths averted and cost per life saved by scaling up mRNA COVID-19 vaccination in low-income and lower-middle-income countries in the COVID-19 Omicron variant era: a modelling study.

      Savinkina, Alexandra; Bilinski, Alyssa; Fitzpatrick, Meagan; Paltiel, A David; Rizvi, Zain; Salomon, Joshua; Thornhill, Thomas; Gonsalves, Gregg (2022-09-13)
      Objectives: While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries (LICs) has received a full primary vaccine series, compared with over 70% of the population of high-income nations. Design: We used economic and epidemiological models, parameterised with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programmes in LICs and lower-middle-income countries (LMICs) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2. Setting: Low-income and lower-middle-income nations. Main outcome measures: Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs. Findings: Globally, universal vaccination in LIC/LMIC with three doses of an mRNA vaccine would result in an estimated 1.5 million COVID-19 deaths averted with a total estimated cost of US$61 billion and an estimated cost-per-COVID-19 death averted of US$40 800 (sensitivity analysis range: US$7400-US$81 500). Lower estimated infection fatality ratios, higher cost-per-dose and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis. Conclusions: Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life. Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.
    • Durability of protection and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) COVID-19 vaccine over 6 months.

      Sobieszczyk, Magdalena E; Maaske, Jill; Falsey, Ann R; Sproule, Stephanie; Robb, Merlin L; Frenck, Robert W; Tieu, Hong-Van; Mayer, Kenneth H; Corey, Lawrence; Neuzil, Kathleen M; et al. (2022-09-15)
      Background. We report updated safety, efficacy, and immunogenicity of AZD1222 (ChAdOx1 nCoV-19) from an ongoing phase 3 trial. Methods. Adults at increased risk of SARS-CoV-2 infection were randomized (2:1), stratified by age, to receive 2 doses of AZD1222 or placebo. The primary efficacy end point was confirmed SARS-CoV-2 reverse-transcriptase PCR–positive (RT-PCR–positive) symptomatic COVID-19 at 15 or more days after a second dose in baseline SARS-CoV-2–seronegative participants. The 21,634 and 10,816 participants were randomized to AZD1222 and placebo, respectively. Findings. Data cutoff for this analysis was July 30, 2021; median follow-up from second dose was 78 and 71 days for the double-blind period (censoring at unblinding or nonstudy COVID-19 vaccination) and 201 and 82 days for the period to nonstudy COVID-19 vaccination (regardless of unblinding) in the AZD1222 and placebo groups, respectively. For the primary efficacy end point in the double-blind period (141 and 184 events; incidence rates: 39.2 and 118.8 per 1,000 person years), vaccine efficacy was 67.0% (P < 0.001). In the period to nonstudy COVID-19 vaccination, incidence of events remained consistently low and stable through 6 months in the AZD1222 group; for the primary efficacy end point (328 and 219 events; incidence rates: 36.4, 108.4) and severe/critical disease (5 and 13 events; incidence rates: 0.6, 6.4), respective vaccine efficacy estimates were 65.1% and 92.1%. AZD1222 elicited humoral immune responses over time, with waning at day 180. No emergent safety issues were seen. Conclusion. AZD1222 is safe and well tolerated, demonstrating durable protection and immunogenicity with median follow-up (AZD1222 group) of 6 months.