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Article ; Online: Volume and Severity of Pediatric COVID-19 Hospitalizations in the United States.

Milliren, Carly E / Ozonoff, Al

Hospital pediatrics

2023 Volume 13, Issue 4, Page(s) e75–e80

Abstract: Objectives: Using administrative data from pediatric hospitals in the United States, we examined trends in coronavirus disease 2019 (COVID-19) hospitalizations and severity of disease among children.: Methods: We extracted data from the Pediatric ... ...

Abstract	Objectives: Using administrative data from pediatric hospitals in the United States, we examined trends in coronavirus disease 2019 (COVID-19) hospitalizations and severity of disease among children. Methods: We extracted data from the Pediatric Health Information System for hospitalized patients less than 12 years old with COVID-19 (identified by primary or secondary International Classification of Diseases-10 diagnosis code U07.1) admitted from April 2020 to August 2022. We examined weekly trends in COVID hospitalization volume overall and by ICU utilization as a measure of severe disease and by COVID diagnosis hierarchy (primary versus secondary) as a proxy for incidental admissions. We estimated the annualized trend in the ratio of hospitalizations requiring, versus not requiring, ICU care and the trend in ratio of hospitalizations with a primary versus secondary COVID diagnosis. Results: We included 38 160 hospitalizations across 45 hospitals. Median age was 2.4 years (interquartile range = 0.7-6.6). Median length of stay was 2.0 days (interquartile range = 1-4). ICU-level care was required for 18.9% and 53.8% had a primary diagnosis of COVID-19. The ratio of ICU to non-ICU admissions declined by 14.5% annually (95% confidence interval: -21.7% to -7.26%; P < .001), whereas the ratio of primary to secondary diagnosis was stable (11.7% annually; 95% confidence interval: -8.83% to 32.4%; P = .26). Conclusions: Periodic increases in pediatric COVID-19 hospitalizations with are evident. However, there is no evidence of corresponding increase in severity of illness that may provide context for recent reports of increasing pediatric COVID hospitalizations in addition to health policy implications.
MeSH term(s)	Child ; Humans ; United States/epidemiology ; Child, Preschool ; COVID-19/epidemiology ; COVID-19/therapy ; Hospitalization ; Hospitals, Pediatric
Language	English
Publishing date	2023-03-09
Publishing country	United States
Document type	Journal Article
ISSN	2154-1671
ISSN (online)	2154-1671
DOI	10.1542/hpeds.2022-006962
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Article: Soft tissue, joint, and bone manifestations of AL amyloidosis: clinical presentation, molecular features, and survival.

Prokaeva, Tatiana / Spencer, Brian / Kaut, Maurya / Ozonoff, Al / Doros, Gheorghe / Connors, Lawreen H / Skinner, Martha / Seldin, David C

Arthritis and rheumatism

2007 Volume 56, Issue 11, Page(s) 3858–3868

Abstract: Objective: To characterize symptoms and signs of AL amyloidosis that may bring patients ... features of soft tissue and bone involvement were assessed in 191 patients with AL amyloidosis. V(L ... in this type of AL amyloidosis. Survival time was initially longer in patients with dominant soft tissue and ...

Abstract	Objective: To characterize symptoms and signs of AL amyloidosis that may bring patients to the attention of rheumatologists, evaluate Ig V(L) gene usage in this subgroup of patients, and assess the impact of soft tissue and bone involvement and V(L) gene usage on survival. Methods: Clinical features of soft tissue and bone involvement were assessed in 191 patients with AL amyloidosis. V(L) gene sequencing was carried out to determine light-chain family, rate of somatic mutation, and evidence of antigen selection. The association of soft tissue and bone involvement with V(L) gene usage was assessed by logistic regression analysis, and survival time was analyzed using log rank tests and Cox regression models. Results: Soft tissue and bone involvement occurred in 42.9% of the patients, and 9.4% had dominant soft tissue and bone involvement. The most common manifestations were submandibular gland enlargement, macroglossia, and carpal tunnel syndrome. Dominant soft tissue and bone involvement was significantly associated with V(L)kappaI gene usage. Mutation rate and evidence of antigen selection in the V(L) genes were not found to be confounding factors, providing evidence against a contribution of autoimmunity in this type of AL amyloidosis. Survival time was initially longer in patients with dominant soft tissue and bone involvement than in patients with other dominant organ involvement; however, this difference diminished over time. Conclusion: Amyloid infiltration into soft tissue, joints, periarticular structures, and bones can bring patients with AL amyloidosis to the attention of rheumatologists. Recognition of the presenting symptoms is essential for accurate diagnosis and appropriate treatment, since the long-term outlook for untreated patients with dominant soft tissue and bone involvement is not better than that for patients with other dominant features of AL amyloidosis.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Amyloidosis, Familial/genetics ; Amyloidosis, Familial/mortality ; Amyloidosis, Familial/pathology ; Bone and Bones/pathology ; Carpal Tunnel Syndrome/genetics ; Carpal Tunnel Syndrome/mortality ; Carpal Tunnel Syndrome/pathology ; Female ; Humans ; Immunoglobulin Light Chains/genetics ; Immunoglobulin Variable Region/genetics ; Incidence ; Joints/pathology ; Macroglossia/genetics ; Macroglossia/mortality ; Macroglossia/pathology ; Male ; Middle Aged ; Multiple Myeloma/genetics ; Multiple Myeloma/mortality ; Multiple Myeloma/pathology ; Proportional Hazards Models ; Risk Factors ; Submandibular Gland/pathology ; Submandibular Gland Diseases/genetics ; Submandibular Gland Diseases/mortality ; Submandibular Gland Diseases/pathology ; Tongue/pathology
Chemical Substances	Immunoglobulin Light Chains ; Immunoglobulin Variable Region
Language	English
Publishing date	2007-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	127294-9
ISSN	1529-0131 ; 0004-3591 ; 2326-5191
ISSN (online)	1529-0131
ISSN	0004-3591 ; 2326-5191
DOI	10.1002/art.22959
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Article ; Online: Increased Pediatric Respiratory Syncytial Virus Case Counts Following the Emergence of Severe Acute Respiratory Syndrome Coronavirus 2 Can Be Attributed to Changes in Testing.

Petros, Brittany A / Milliren, Carly E / Sabeti, Pardis C / Ozonoff, Al

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2024

Abstract: Background: Respiratory syncytial virus (RSV) circulation dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naїve pediatric population increased ... ...

Abstract	Background: Respiratory syncytial virus (RSV) circulation dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naїve pediatric population increased during the period of low transmission. However, the evidence supporting this hypothesis is limited, and the role of changing testing practices in the perceived surge has not been comprehensively evaluated. Methods: We conducted a multicenter, retrospective analysis of 342 530 RSV encounters and 980 546 RSV diagnostic tests occurring at 32 US pediatric hospitals in 2013-2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and test volume and to quantify changes in the proportions of patients requiring hospitalization, intensive care, or mechanical ventilation. We quantified the fraction of the shifts in case counts and in the age of diagnosed patients attributable to changes in testing. Results: RSV patient volume increased 2.4-fold (95% confidence interval [CI]: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Shifts in patient volume and in patient age were largely attributable to increased testing. The proportions of patients with RSV that required hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. Conclusions: A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. These findings warrant a critical assessment of the immunity debt hypothesis and highlight the importance of considering the testing denominator when surveillance strategies are dynamic.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciae140
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Article: Increased pediatric RSV case counts following the emergence of SARS-CoV-2 are attributable to increased testing.

Petros, Brittany A / Milliren, Carly E / Sabeti, Pardis C / Ozonoff, Al

medRxiv : the preprint server for health sciences

2024

Abstract: Background: The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naive pediatric population ... ...

Abstract	Background: The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naive pediatric population increased during the period of low transmission, resulting in a subsequent increased risk of infection. However, the evidence supporting this hypothesis is limited, and no studies have comprehensively evaluated the role of changing respiratory viral testing practices in the perceived surge. Methods: We conducted a multicenter, retrospective analysis of 342,530 RSV encounters and 980,546 RSV diagnostic tests occurring at 32 United States pediatric hospitals between 2013 and 2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and testing volume, and to quantify changes in the proportions of patients admitted from the emergency department (ED), admitted to the intensive care unit (ICU), and receiving mechanical ventilation. We quantified the fraction of the observed shifts in case counts and in the age of diagnosed patients attributable to changes in RSV testing practices. Finally, we analyzed 524,404 influenza virus encounters and 1,768,526 influenza diagnostic tests to address the specificity of the findings to RSV. Findings: RSV patient volume increased 2.4-fold (95% CI: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase, and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Over two-thirds of the apparent shifts in patient volume and in patient age were attributable to increased testing, which was concentrated among older pediatric patients. The proportions of patients with RSV requiring hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. These declines were not observed for patients with influenza virus. Interpretation: A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. We identify expected consequences of increased testing, including the diagnosis of less severe cases and a shift in the patient age distribution. These findings warrant a critical assessment of the immunity debt hypothesis, while highlighting the importance of considering the testing denominator when surveillance strategies are dynamic. Funding: National Institutes of Health & Howard Hughes Medical Institute.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.06.24302387
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Article ; Online: Incidence of Hospital-Acquired Conditions During Pediatric Clinical Research Inpatient Hospitalizations: A Matched Cohort Study.

Milliren, Carly E / Denhoff, Erica R / Hahn, Phillip D / Ozonoff, Al

Journal of patient safety

2023 Volume 19, Issue 7, Page(s) 469–477

Abstract: Objectives: In this matched cohort study using data from pediatric hospitals, we compared the incidence of hospital-acquired conditions (HACs) during clinical research hospitalizations to nonresearch hospitalizations.: Methods: Using Pediatric Health ...

Abstract	Objectives: In this matched cohort study using data from pediatric hospitals, we compared the incidence of hospital-acquired conditions (HACs) during clinical research hospitalizations to nonresearch hospitalizations. Methods: Using Pediatric Health Information System data for inpatient discharges January 2017-June 2022, we matched research hospitalizations (identified by International Classification of Diseases, Tenth Revision, diagnosis code) to nonresearch hospitalizations within hospital on age (±3 y), sex, discharge year (±2), and All Patients Refined Diagnosis Related Groups classification, severity of illness (±1), and risk of mortality (±1). We calculated the incidence (per 1000 discharges) and incidence rate (per 10,000 patient days) of HAC identified by International Classification of Diseases, Tenth Revision, codes and compare research versus nonresearch using logistic and Poisson regression, accounting for matching using generalized estimating equations and adjusting for sociodemographic factors and hospital utilization. Results: We matched 7000 research hospitalizations to 26,447 nonresearch from 28 hospitals. Median age was 6.0 years (interquartile range, 10.6 y). Median length of stay was 4.0 days (interquartile range, 11.0 days) with longer stays among research hospitalizations ( P < 0.001). Incidence of HAC among research hospitalizations was 13.1 versus 7.2 per 1000 for nonresearch ( P < 0.001) and incidence rate 6.7 versus 4.5 per 10,000 patient days. Adjusting for sociodemographic and clinical factors, research stays had 1.65 times the odds of any HAC (95% confidence interval, 1.27-2.16; P < 0.001) and 1.38 times the incidence rate (95% confidence interval, 1.09-1.75; P = 0.009). Conclusions: Our findings indicate that pediatric research hospitalizations are more likely to experience HACs compared with nonresearch hospitalizations. These findings have important safety implications for pediatric inpatient clinical research that warrant further study.
MeSH term(s)	Humans ; Child ; Inpatients ; Incidence ; Cohort Studies ; Hospitalization ; Iatrogenic Disease ; Hospitals, Pediatric
Language	English
Publishing date	2023-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2394324-5
ISSN	1549-8425 ; 1549-8417
ISSN (online)	1549-8425
ISSN	1549-8417
DOI	10.1097/PTS.0000000000001159
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Article ; Online: Waning effectiveness of SARS-CoV-2 mRNA vaccines in older adults: a rapid review.

Nanishi, Etsuro / Levy, Ofer / Ozonoff, Al

Human vaccines & immunotherapeutics

2022 Volume 18, Issue 5, Page(s) 2045857

Abstract: The U.S. Centers for Disease Control and Prevention (CDC) and other health agencies have recently recommended a booster dose of COVID-19 vaccines for specific vulnerable groups including adults 65 years and older. There is limited evidence whether ... ...

Abstract	The U.S. Centers for Disease Control and Prevention (CDC) and other health agencies have recently recommended a booster dose of COVID-19 vaccines for specific vulnerable groups including adults 65 years and older. There is limited evidence whether vaccine effectiveness (VE) in older adults decreases over time, especially against severe COVID-19. We performed a rapid review of published studies available through 4 November 2021 that provide effectiveness data on messenger RNA (mRNA) vaccines approved/licensed in the United States and identified eight eligible studies which evaluated VE in older adults. There is evidence of a decline in VE against both severe acute respiratory syndrome coronavirus 2 infection and severe COVID-19 in older adults among studies which analyzed data up to July-October 2021. Our findings suggest that VE diminishes in older adults, which supports the current recommendation for a booster dose in this population.
MeSH term(s)	Aged ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; RNA, Messenger ; SARS-CoV-2/genetics ; United States ; Vaccines, Synthetic ; mRNA Vaccines
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; Vaccines, Synthetic ; mRNA Vaccines
Language	English
Publishing date	2022-03-03
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2664176-8
ISSN	2164-554X ; 2164-5515
ISSN (online)	2164-554X
ISSN	2164-5515
DOI	10.1080/21645515.2022.2045857
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Article ; Online: A Comparison of Methods Examining Time-to-Readmission in the First Year of Life.

Milliren, Carly E / Melvin, Patrice / Ozonoff, Al

Hospital pediatrics

2022 Volume 12, Issue 11, Page(s) 988–994

Abstract: Background and objectives: Readmissions analyses typically calculate time-to-readmission relative to hospital discharge. For newborns, this definition can be challenging when comparing groups with disparate birth stays. We compare 2 approaches to ... ...

Abstract	Background and objectives: Readmissions analyses typically calculate time-to-readmission relative to hospital discharge. For newborns, this definition can be challenging when comparing groups with disparate birth stays. We compare 2 approaches to calculate readmissions and examine 1 year readmissions for newborns with versus without neonatal opioid withdrawal syndrome (NOWS; mean length of stay = 17 vs 2 days). Methods: Using birth discharge data from the Pediatric Health Information System (PHIS), we compared crude and adjusted 1 year readmissions by NOWS diagnosis using Cox regression models predicting time-to-readmission from: (1) birth discharge; and (2) birth (day-of-life), with left truncation allowing for delayed entry into the at-risk period at birth discharge. Results: We included N = 155 885 birth discharges (n = 1467 with NOWS). At 1 year, 10% of infants with NOWS versus 6% without had been readmitted. Readmission risk was highest within 1 week since discharge or birth for newborns without NOWS, whereas those with NOWS were at higher risk later into infancy. NOWS was associated with a higher adjusted hazard of 1 year readmissions since discharge (adjusted hazard ratio [aHR]=1.58; 95% CI: 1.20-2.08) and a higher adjusted hazard of 1 year readmissions since birth (aHR = 1.56; 95% CI: 1.21-2.03). Estimates vary by choice of index date, particularly at early time-points, converging later into infancy. Conclusions: Our findings underscore the importance of methodological decisions for newborn readmissions. Although results were similar at 1 year with nearly identical adjusted hazards, approaches differed substantially through the neonatal period.
MeSH term(s)	Infant ; Infant, Newborn ; Humans ; Child ; Patient Readmission ; Length of Stay ; Patient Discharge ; Time ; Risk Factors
Language	English
Publishing date	2022-10-18
Publishing country	United States
Document type	Journal Article
ISSN	2154-1671
ISSN (online)	2154-1671
DOI	10.1542/hpeds.2021-006406
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Article ; Online: Increased pediatric RSV case counts following the emergence of SARS-CoV-2 are attributable to increased testing

Petros, Brittany A. / Milliren, Carly E. / Sabeti, Pardis C. / Ozonoff, Al

medRxiv

Abstract: Background: The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The immunity debt hypothesis proposes that the RSV-naive pediatric population increased ... ...

Abstract	Background: The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The immunity debt hypothesis proposes that the RSV-naive pediatric population increased during the period of low transmission, resulting in a subsequent increased risk of infection. However, the evidence supporting this hypothesis is limited, and no studies have comprehensively evaluated the role of changing respiratory viral testing practices in the perceived surge. Methods: We conducted a multicenter, retrospective analysis of 342,530 RSV encounters and 980,546 RSV diagnostic tests occurring at 32 United States pediatric hospitals between 2013 and 2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and testing volume, and to quantify changes in the proportions of patients admitted from the emergency department (ED), admitted to the intensive care unit (ICU), and receiving mechanical ventilation. We quantified the fraction of the observed shifts in case counts and in the age of diagnosed patients attributable to changes in RSV testing practices. Finally, we analyzed 524,404 influenza virus encounters and 1,768,526 influenza diagnostic tests to address the specificity of the findings to RSV. Findings: RSV patient volume increased 2.4-fold (95% CI: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase, and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Over two-thirds of the apparent shifts in patient volume and in patient age were attributable to increased testing, which was concentrated among older pediatric patients. The proportions of patients with RSV requiring hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. These declines were not observed for patients with influenza virus. Interpretation: A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. We identify expected consequences of increased testing, including the diagnosis of less severe cases and a shift in the patient age distribution. These findings warrant a critical assessment of the immunity debt hypothesis, while highlighting the importance of considering the testing denominator when surveillance strategies are dynamic.
Keywords	covid19
Language	English
Publishing date	2024-02-06
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2024.02.06.24302387
Database	COVID19

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Article ; Online: Bell's palsy and SARS-CoV-2 vaccines-an unfolding story - Authors' reply.

Ozonoff, Al / Nanishi, Etsuro / Levy, Ofer

The Lancet. Infectious diseases

2021 Volume 21, Issue 9, Page(s) 1211–1212

MeSH term(s)	Acyclovir ; Bell Palsy ; COVID-19 ; COVID-19 Vaccines ; Humans ; SARS-CoV-2
Chemical Substances	COVID-19 Vaccines ; Acyclovir (X4HES1O11F)
Language	English
Publishing date	2021-06-07
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(21)00323-6
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Article ; Online: Bell's palsy and SARS-CoV-2 vaccines.

Ozonoff, Al / Nanishi, Etsuro / Levy, Ofer

The Lancet. Infectious diseases

2021 Volume 21, Issue 4, Page(s) 450–452

MeSH term(s)	Bell Palsy/epidemiology ; Bell Palsy/etiology ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Humans ; Influenza Vaccines/adverse effects ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; United States/epidemiology ; United States Food and Drug Administration
Chemical Substances	COVID-19 Vaccines ; Influenza Vaccines
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(21)00076-1
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