Browsing by Author "Davis, Jonathan M."

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    Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults - VISION Network, 10 States, December 2021-March 2022
    (Center for Disease Control, 2022-04-01) Natarajan, Karthik; Prasad, Namrata; Dascomb, Kristin; Irving, Stephanie A.; Yang, Duck-Hye; Gaglani, Manjusha; Klein, Nicola P.; DeSilva, Malini B.; Ong, Toan C.; Grannis, Shaun J.; Stenehjem, Edward; Link-Gelles, Ruth; Rowley, Elizabeth A.; Naleway, Allison L.; Han, Jungmi; Raiyani, Chandni; Vazquez Benitez, Gabriela; Rao, Suchitra; Lewis, Ned; Fadel, William F.; Grisel, Nancy; Griggs, Eric P.; Dunne, Margaret M.; Stockwell, Melissa S.; Mamawala, Mufaddal; McEvoy, Charlene; Barron, Michelle A.; Goddard, Kristin; Valvi, Nimish R.; Arndorfer, Julie; Patel, Palak; Mitchell, Patrick K.; Smith, Michael; Kharbanda, Anupam B.; Fireman, Bruce; Embi, Peter J.; Dickerson, Monica; Davis, Jonathan M.; Zerbo, Ousseny; Dalton, Alexandra F.; Wondimu, Mehiret H.; Azziz-Baumgartner, Eduardo; Bozio, Catherine H.; Reynolds, Sue; Ferdinands, Jill; Williams, Jeremiah; Schrag, Stephanie J.; Verani, Jennifer R.; Ball, Sarah; Thompson, Mark G.; Dixon, Brian E.; Community and Global Health, Richard M. Fairbanks School of Public Health
    CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome† (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network§ determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits¶ and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.
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    Protection of Two and Three mRNA Vaccine Doses Against Severe Outcomes Among Adults Hospitalized With COVID-19-VISION Network, August 2021 to March 2022
    (Oxford, 2023-04-15) DeSilva, Malini B.; Mitchell, Patrick K.; Klein, Nicola P.; Dixon, Brian E.; Tenforde, Mark W.; Thompson, Mark G.; Naleway, Allison L.; Grannis, Shaun G.; Ong, Toan C.; Natarajan, Karthik; Reese, Sarah E.; Zerbo, Ousseny; Kharbanda, Anupam B.; Patel, Palak; Stenehjem, Edward; Raiyani, Chandni; Irving, Stephanie A.; Fadel, William F.; Rao, Suchitra; Han, Jungmi; Reynolds, Sue; Davis, Jonathan M.; Lewis, Ned; McEvoy, Charlene; Dickerson, Monica; Dascomb, Kristin; Valvi, Nimish R.; Barron, Michelle A.; Goddard, Kristin; Vazquez-Benitez, Gabriela; Grisel, Nancy; Mamwala, Mufaddal; Embi, Peter J.; Fireman, Bruce; Essien, Inih J.; Griggs, Eric P.; Arndorfer, Julie; Gaglani, Manjusha; Biostatistics and Health Data Science, School of Medicine
    Background We assessed coronavirus disease 2019 (COVID-19) vaccination impact on illness severity among adults hospitalized with COVID-19, August 2021–March 2022. Methods We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19–like illness and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing. We calculated odds ratios (ORs) for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation. Results We included 27 149 SARS-CoV-2–positive hospitalizations. During both Delta- and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR, 0.52 [95% CI, .28–.96]; Omicron OR, 0.69 [95% CI, .54–.87]). During both periods, risk of in-hospital death was lower among vaccinated compared with unvaccinated patients but ORs overlapped across vaccination strata. We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients. Conclusions COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated.
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    Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder
    (American Medical Association, 2023) Maron, Jill L.; Kingsmore, Stephen; Gelb, Bruce D.; Vockley, Jerry; Wigby, Kristen; Bragg, Jennifer; Stroustrup, Annemarie; Poindexter, Brenda; Suhrie, Kristen; Kim, Jae H.; Diacovo, Thomas; Powell, Cynthia M.; Trembath, Andrea; Guidugli, Lucia; Ellsworth, Katarzyna A.; Reed, Dallas; Kurfiss, Anne; Breeze, Janis L.; Trinquart, Ludovic; Davis, Jonathan M.; Pediatrics, School of Medicine
    Importance: Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene-sequencing test provides comparable molecular diagnostic yields and times to return of results. Objective: To compare outcomes of genomic sequencing with those of a targeted neonatal gene-sequencing test. Design, setting, and participants: The Genomic Medicine for Ill Neonates and Infants (GEMINI) study was a prospective, comparative, multicenter study of 400 hospitalized infants younger than 1 year of age (proband) and their parents, when available, suspected of having a genetic disorder. The study was conducted at 6 US hospitals from June 2019 to November 2021. Exposure: Enrolled participants underwent simultaneous testing with genomic sequencing and a targeted neonatal gene-sequencing test. Each laboratory performed an independent interpretation of variants guided by knowledge of the patient's phenotype and returned results to the clinical care team. Change in clinical management, therapies offered, and redirection of care was provided to families based on genetic findings from either platform. Main outcomes and measures: Primary end points were molecular diagnostic yield (participants with ≥1 pathogenic variant or variant of unknown significance), time to return of results, and clinical utility (changes in patient care). Results: A molecular diagnostic variant was identified in 51% of participants (n = 204; 297 variants identified with 134 being novel). Molecular diagnostic yield of genomic sequencing was 49% (95% CI, 44%-54%) vs 27% (95% CI, 23%-32%) with the targeted gene-sequencing test. Genomic sequencing did not report 19 variants found by the targeted neonatal gene-sequencing test; the targeted gene-sequencing test did not report 164 variants identified by genomic sequencing as diagnostic. Variants unidentified by the targeted genomic-sequencing test included structural variants longer than 1 kilobase (25.1%) and genes excluded from the test (24.6%) (McNemar odds ratio, 8.6 [95% CI, 5.4-14.7]). Variant interpretation by laboratories differed by 43%. Median time to return of results was 6.1 days for genomic sequencing and 4.2 days for the targeted genomic-sequencing test; for urgent cases (n = 107) the time was 3.3 days for genomic sequencing and 4.0 days for the targeted gene-sequencing test. Changes in clinical care affected 19% of participants, and 76% of clinicians viewed genomic testing as useful or very useful in clinical decision-making, irrespective of a diagnosis. Conclusions and relevance: The molecular diagnostic yield for genomic sequencing was higher than a targeted neonatal gene-sequencing test, but the time to return of routine results was slower. Interlaboratory variant interpretation contributes to differences in molecular diagnostic yield and may have important consequences for clinical management.
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    Recommendations for the design of therapeutic trials for neonatal seizures
    (Springer Nature, 2019-06) Soul, Janet S.; Pressler, Ronit; Allen, Marilee; Boylan, Geraldine; Rabe, Heike; Portman, Ron; Hardy, Pollyanna; Zohar, Sarah; Romero, Klaus; Tseng, Brian; Bhatt-Mehta, Varsha; Hahn, Cecil; Denne, Scott; Auvin, Stephane; Vinks, Alexander; Lantos, John; Marlow, Neil; Davis, Jonathan M.; Pediatrics, School of Medicine
    Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.