Geographic Progression of Infant Respiratory Syncytial Virus Associated Bronchiolitis Across the United States Before and Since the Onset of COVID-19: Results From Four Health Systems, 2015-2023.

BACKGROUND: Respiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west. Public health measures implemented due to the COVID-19 pandemic disrupted viral transmission across the nation and altered the expected seasonality of RSV. The impact of these changes on the geographic progression of infant RSV bronchiolitis across the United States has not been described. METHODS: Here, we used clinical and viral surveillance data from four health care systems located in different regions of the United States to describe the geographic progression of infant RSV bronchiolitis across the country from 2015 to 2023. RESULTS: Prior to widespread circulation of SARS-CoV-2, infant RSV bronchiolitis followed an established geographic pattern associated with seasonal epidemics originating in Florida and spreading north (North Carolina and New York) and later westward (Nevada). Although public health and social measures implemented during the COVID-19 pandemic disrupted the seasonality of RSV disease, infant RSV bronchiolitis epidemics progressed across the nation in a pattern identical to the prepandemic era. CONCLUSIONS: Our findings highlight the importance of ongoing clinical and viral surveillance to optimally track the onset of RSV epidemics and allow health care systems to prepare for expected RSV bronchiolitis surges.

Healthcare Utilization Among Infants Covered by Medicaid and Newly Diagnosed With Respiratory Syncytial Virus.

Background: Infants covered by Medicaid have higher respiratory syncytial virus (RSV) hospitalization rates than those with commercial insurance, but findings are limited to the inpatient setting. This birth cohort study describes healthcare encounters for RSV across all settings among infants covered by Medicaid and the Children's Health Insurance Program. Methods: Medicaid claims for infants born and residing in Arizona (AZ), California (CA), Florida (FL), Michigan (MI), North Carolina (NC), New York (NY), and Texas (TX) were analyzed for first diagnosis of RSV in 2016-2018 using International Classification of Diseases, Tenth Revision codes. Encounters on the day of first diagnosis were examined by setting in 7 states and by setting and race in CA, FL, and NC. Results: A total of 80 945 infants were diagnosed with RSV in 7 states in 2016-2018. The highest encounter rates for first RSV diagnosis were in the emergency department (ED) in 5 states (11.0-33.4 per 1000 in AZ, CA, FL, MI, and NY) and outpatient setting in 2 states (54.8 and 68.5 per 1000 in TX and NC). Significantly higher outpatient encounter rates were found in CA and NC for White infants compared to non-White infants. In NC, ED encounter rates were significantly higher for non-White infants than White infants, whereas in CA, the rates were comparable. In these 2 states, hospitalization rates were similar across groups. In FL, compared with White infants, non-White infants had significantly higher encounter rates in each setting on the day of first RSV diagnosis. Conclusions: This is the first study to describe the burden of RSV by setting and race. Medicaid infants who are newly diagnosed with RSV have the highest burden in ED and outpatient settings.

Trends in RSV testing patterns among infants presenting with bronchiolitis: Results from four United States health systems, 2015-2023.

BACKGROUND: Bronchiolitis due to respiratory syncytial virus (RSV) is the leading cause of hospitalization among American infants. The overall burden of RSV among infants has been historically under-estimated due to variable testing practices, particularly in the outpatient setting. Universal masking and social distancing implemented during the coronavirus disease 2019 (COVID-19) pandemic altered RSV seasonality, however potential consequences on RSV testing practices across different healthcare settings and sociodemographic groups have not been described. Variable testing practices could also affect accurate assessment of the effects of two recently approved RSV preventative agents targeting infants. METHODS: Utilizing real-time clinical and viral surveillance, we examined RSV testing practices among infants with bronchiolitis within four United States healthcare systems across different healthcare settings and sociodemographic groups pre- and post-COVID-19. RESULTS: RSV testing among infants with bronchiolitis increased since 2015 within each healthcare system across all healthcare settings and sociodemographic groups, with a more dramatic increase since the COVID-19 pandemic. Outpatient testing remained disproportionately low compared to hospital-based testing, although there were no major differences in testing frequency among sociodemographic groups in either setting. CONCLUSIONS: Although RSV testing increased among infants with bronchiolitis, relatively low outpatient testing rates remain a key barrier to accurate RSV surveillance.

Overview of global real-world data sources for pediatric pharmacoepidemiologic research.

PURPOSE: Given limited information available on real-world data (RWD) sources with pediatric populations, this study describes features of globally available RWD sources for pediatric pharmacoepidemiologic research. METHODS: An online questionnaire about pediatric RWD sources and their attributes and capabilities was completed by members and affiliates of the International Society for Pharmacoepidemiology and representatives of nominated databases. All responses were verified by database representatives and summarized. RESULTS: Of 93 RWD sources identified, 55 unique pediatric RWD sources were verified, including data from Europe (47%), United States (38%), multiregion (7%), Asia-Pacific (5%), and South America (2%). Most databases had nationwide coverage (82%), contained electronic health/medical records (47%) and/or administrative claims data (42%) and were linkable to other databases (65%). Most (71%) had limited outside access (e.g., by approval or through local collaborators); only 10 (18%) databases were publicly available. Six databases (11%) reported having >20 million pediatric observations. Most (91%) included children of all ages (birth until 18th birthday) and contained outpatient medication data (93%), while half (49%) contained inpatient medication data. Many databases captured vaccine information for children (71%), and one-third had regularly updated data on pediatric height (31%) and weight (33%). Other pediatric data attributes captured include diagnoses and comorbidities (89%), lab results (58%), vital signs (55%), devices (55%), imaging results (42%), narrative patient histories (35%), and genetic/biomarker data (22%). CONCLUSIONS: This study provides an overview with key details about diverse databases that allow researchers to identify fit-for-purpose RWD sources suitable for pediatric pharmacoepidemiologic research.

Dietary eating patterns, dairy consumption, and anxiety: A systematic literature review.

BACKGROUND: Nutrition affects both physical and mental health but evidence is mixed regarding potential associations between anxiety and diet, particularly dairy consumption. We conducted a systematic literature review (SLR) of dairy consumption and/or various dietary patterns and risk of anxiety. METHODS: Literature searches were conducted in PubMed and Embase. All study designs except case reports, small case series, and SLRs were considered for inclusion. Reference lists of previously published SLRs were reviewed for any relevant additional studies. Studies of populations without dairy sensitivities exploring the association between dietary patterns and/or dairy consumption and anxiety published through May 2022 were identified using predefined eligibility criteria. Study quality was determined using the Academy of Nutrition and Dietetics Quality Criteria Checklist. RESULTS: For this SLR, 132 studies were included; 80 were cross-sectional. Studies examined different dietary patterns (e.g., Mediterranean, gluten-free) and anxiety using various anxiety scales, with 19 studies specifically reporting on whole dairy consumption and anxiety. Dairy consumption was significantly associated with a lower risk of anxiety in 7 studies, while the remaining 12 studies showed no significant associations. Evidence was mixed for the association between various dietary patterns and anxiety, but more studies observed a lower risk of anxiety with greater adherence to "healthy" diets (e.g., Mediterranean, diet quality score, vegetarian/vegan) than a higher risk. Notable heterogeneity in study populations, time periods, geographical locations, dietary assessment methods, and anxiety scales was observed. CONCLUSIONS: The results of this SLR suggest a potential link between diet including diary consumption and anxiety, but future studies, especially with longitudinal designs that measure diet and anxiety at several timepoints and comprehensively adjust for confounders, are needed to fully understand the relationship between diet and anxiety.

Systematic Literature Review of the Prevalence and Prognostic Value of Delta-Like Ligand 3 Protein Expression in Small Cell Lung Cancer.

BACKGROUND: Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer (SCLC), a subtype accounting for 15% of lung cancer cases. OBJECTIVE: A systematic literature review (SLR) was conducted to understand the prevalence and prognostic impact of DLL3 expression on survival of patients with SCLC and treatment response. PATIENTS AND METHODS: Systematic literature searches were conducted across multiple databases to capture studies of any SCLC population that evaluated DLL3 expression. Specific outcomes of interest included prevalence of DLL3 expression, method of expression analysis, and impact on outcome, including treatment response and survival (overall, progression-free, disease-free) according to varying levels of DLL3 expression/positivity. Standard risk of bias tools were used to evaluate study quality. RESULTS: Among the 30 included studies, the most common DLL3 testing method was immunohistochemistry (N = 26, 86.7%). For comparability, results focused on the 13 (22.3%) studies that used the Ventana DLL3 (SP347) immunohistochemistry assay. The prevalence of DLL3 positivity ranged from 80.0-93.5% for studies using a threshold of ≥ 1% of tumor cells (N = 4) and 58.3-91.1% for studies with a ≥ 25% threshold (N = 4). DLL3 expression was generally categorized as high using cutoffs of ≥ 50% (prevalence range: 45.8-79.5%; N = 6) or ≥ 75% (prevalence range: 47.3-75.6%; N = 5) of cells with positivity. Two studies used an H-score of ≥ 150 to define high DLL3 expression with prevalence ranging from 33.3-53.1%. No consistent associations were seen between DLL3 expression level and patient age, sex, smoking history, or disease stage. Two studies reported change in DLL3 expression category (high versus low) before and after chemotherapy. No statistically significant differences were reported between DLL3 expression groups and survival (overall, progression-free, or disease-free) or treatment response. CONCLUSIONS: There is a high prevalence of DLL3 expression in SCLC. Further research and analytical methods may help to characterize different populations of patients with SCLC based on DLL3 expression. While no significant prognostic factor in the included studies was identified, additional cohort studies using standardized methodology, with longer follow-up, are needed to better characterize any potential differences in patient survival or response by DLL3 expression level in SCLC.

Epidemiology of RSV Bronchiolitis Among Young Children in Central New York Before and After the Onset of the COVID-19 Pandemic.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalizations among infants in the United States. Unpredictability in RSV seasonality has occurred following the onset of the coronavirus disease 2019 (COVID-19) pandemic. Local surveillance networks can enhance the ability to appropriately time prophylaxis when exposure risk is highest. METHODS: A retrospective, cohort study was conducted to describe the epidemiologic patterns of RSV disease among outpatient, emergency department and inpatient encounters in children <5 years in Central New York before and after the onset of the COVID-19 pandemic. Local data were collected from October 2015 to January 2023 and compared to state-level data. Linear regression models were used to identify clinical and sociodemographic differences before and after the pandemic. RESULTS: Local variation in RSV seasonality was noted prior to the COVID-19 pandemic, however highly atypical circulation patterns appeared in the post-COVID-19 era. Since March 2020, patterns for local and state-defined RSV seasons have remained atypical (local season onset in 2021: week 27 and 2022: week 27; state season onset in 2021: week 31 and 2022: week 38). After adjusting for increases in testing, RSV bronchiolitis cases were not significantly different during pre- and post-pandemic eras. In comparison to the 2021 bronchiolitis season, the 2022 season had a higher proportion of RSV cases despite decreased testing. CONCLUSIONS: Temporal patterns for RSV have shifted during the COVID-19 pandemic. Local surveillance networks may be advantageous in trending community-level RSV activity to optimize prophylaxis administration. Changes in RSV testing patterns occurred throughout the study period and should be accounted for when describing infant and childhood RSV disease.

Scoping Review of Employer-Led Research Using Employee Health Claims Data.

Employers may evaluate employee claims data for various reasons, including assessment of medical insurance and wellness plan efficacy, monitoring employee health trends, and identifying focus areas for wellness measures. The objective of this scoping review (ScR) is to describe the available literature reporting the use, applications, and outcomes of employee health claims data by self-insured employers. The ScR was conducted in a stepwise manner using an established framework: identifying the research question, identifying and selecting relevant studies, charting the data, and collating and reporting results. Literature searches were conducted in PubMed and Embase. Studies of self-insured employee populations that were conducted by the employer/s through May 2022 were identified using predefined criteria. Forty-one studies were included. The majority (90%) were cohort study designs; most employers (51%) were in industries such as aluminum production and health insurance providers. Twenty-four (59%) studies supplemented claims data with other sources such as human resource data to evaluate programs and/or health outcomes. A range of exposures (eg, chronic conditions, wellness program participation) and outcomes (eg, rates or costs of conditions, program effectiveness) were considered. Among the 25 studies that reported on patient confidentiality and privacy, 68% indicated institutional review board approval and 48% reported use of deidentified data. Many self-insured employers have used employee health claims data to gain insights into their employees' needs and health care utilization. These data can be used to identify potential improvements for wellness and other targeted programs to improve employee health and decrease absenteeism.

Biomarker expression and survival in patients with non-small cell lung cancer receiving adjuvant chemotherapy in Denmark.

INTRODUCTION: Programmed cell death ligand-1 (PD-L1) expression may help identify patients with non-small cell lung cancer (NSCLC) who would benefit from immunotherapy. We assessed PD-L1 expression, and epidermal growth factor receptor (EGFR) and V-Ki-Ras2 Kirsten rat sarcoma (KRAS) mutations in NSCLC patients receiving adjuvant chemotherapy. METHODS: Data for stage IB/II/IIIA NSCLC patients (diagnosed: 2001-2012) were retrieved from Danish population-based registries. Tumor tissue samples were tested for PD-L1 expression using VENTANA PD-L1 (SP263) Assay in tumor cells (TC) at ≥25% cutoff and immune cells (IC) at ≥1% and ≥25% cutoffs. KRAS and EGFR mutations were tested using PCR-based assays. Follow-up began 120 days after diagnosis until death/emigration/January 1, 2015, whichever came first. Using Cox proportional hazard regression, hazard ratios (HRs) were computed for overall survival (OS) for each biomarker, adjusting for age, sex, histology, comorbidities, and tissue specimen age. RESULTS: Among 391 patients identified, 40.4% had stage IIIA disease, 49.9% stage II, and 8.7% stage IB. PD-L1-TC was observed in 38% of patients, EGFR mutations in 4%, and KRAS mutations in 29%. KRAS mutations were more frequent among patients with PD-L1 TC≥25% versus TC<25% (37% versus 24%). OS was not associated with PD-L1 TC≥25% versus TC<25% (stage II: adjusted HR = 1.15 [95% confidence interval: 0.66-2.01]; stage IIIA: 0.72 [0.44-1.19]). No significant association was observed with OS and PD-L1-IC ≥1% and ≥25%. EGFR and KRAS mutations were not associated with a prognostic impact. CONCLUSION: A prognostic impact for NSCLC patients receiving adjuvant chemotherapy was not associated with PD-L1 expression, or with EGFR and KRAS mutations.

Benefit-risk of coffee consumption and all-cause mortality: A systematic review and disability adjusted life year analysis.

BACKGROUND: Recommendations and guidance from scientific bodies do not provide clear messages about potential health risks or benefits of coffee consumption. Numerous studies have demonstrated inverse (beneficial) effects of coffee consumption for many adverse outcomes such as cancer and cardiovascular disease; fewer studies demonstrate risks. However, the risk-benefit relationship has not yet been fully assessed using quantitative metrics preferred by policy makers (disability-adjusted life years [DALYs]). OBJECTIVE: Conduct a quantitative analysis of the risk-benefit for coffee consumption and all-cause mortality using the Benefit-Risk Analysis for Foods (BRAFO) framework and the DALY as a quantitative metric. METHOD: A systematic search and appraisal of meta-analyses investigating coffee consumption and all-cause mortality was conducted. Using the BRAFO framework, evidence was assessed in context of potential risks or benefits associated with the reference scenario - coffee consumption (assessed by varying the consumption level in three analyses) in adults aged 15+ versus the alternative scenario of no coffee consumption. DALYs were used to quantify risks and benefits based on risk ratios from meta-analyses with populations from the United States. RESULTS: Meta-analyses consistently report an inverse (beneficial) relationship between coffee consumption and all-cause mortality; subsequently, even while varying consumption amounts and prevalence of coffee consumption, DALYs calculated consistently demonstrated findings in the direction of prevention of healthy years of life lost with variable magnitude. More than 3.5 million DALYs, or ∼3.35% of estimated years of healthy life lost could be prevented by consuming one cup of coffee per day, up to 4.7% of estimated years of healthy life lost could be prevented at current consumption rates ranging from 1 to 8 cups/day, and even more benefit could be seen (prevention of an estimated 6% of years of healthy life lost) if consumers all drank 3 cups of coffee per day. IMPACT: Policy that directs consumers to avoid drinking coffee may be a detriment to the overall health of the population given the substantial potential benefits of coffee consumption on all-cause mortality for adults.

Respiratory Syncytial Virus During the COVID-19 Pandemic Compared to Historic Levels: A Retrospective Cohort Study of a Health System.

BACKGROUND: Surveillance in 2020-2021 showed that seasonal respiratory illnesses were below levels seen during prior seasons, with the exception of interseasonal respiratory syncytial virus (RSV). METHODS: Electronic health record data of infants aged <1 year visiting the Duke University Health System from 4 October 2015 to 28 March 2020 (pre-COVID-19) and 29 March 2020 to 30 October 2021 (COVID-19) were assessed. International Classification of Diseases-Tenth Revision (ICD-10) codes for RSV (B97.4, J12.1, J20.5, J21.0) and bronchiolitis (RSV codes plus J21.8, J21.9) were used to detail encounters in the inpatient (IP), emergency department (ED), outpatient (OP), urgent care (UC), and telemedicine (TM) settings. RESULTS: Pre-COVID-19, 88% of RSV and 92% of bronchiolitis encounters were seen in ambulatory settings. During COVID-19, 94% and 93%, respectively, occurred in ambulatory settings. Pre-COVID-19, the highest RSV proportion was observed in December-January (up to 38% in ED), while the peaks during COVID-19 were seen in July-September (up to 41% in ED) across all settings. RSV laboratory testing among RSV encounters was low during pre-COVID-19 (IP, 51%; ED, 51%; OP, 41%; UC, 84%) and COVID-19 outside of UC (IP, 33%; ED, 47%; OP, 47%; UC, 87%). Full-term, otherwise healthy infants comprised most RSV encounters (pre-COVID-19, up to 57% in OP; COVID-19, up to 82% in TM). CONCLUSIONS: With the interruption of historical RSV epidemiologic trends and the emergence of interseasonal disease during COVID-19, continued monitoring of RSV is warranted across all settings as the changing RSV epidemiology could affect the distribution of health care resources and public health policy.

Mortality Among US Infants and Children Under 5 Years of Age with Respiratory Syncytial Virus and Bronchiolitis: A Systematic Literature Review.

BACKGROUND: A systematic literature review was conducted to summarize the mortality (overall and by disease severity factors) of US infants and children aged <5 years with respiratory syncytial virus (RSV) or all-cause bronchiolitis (ACB). METHODS: Comprehensive, systematic literature searches were conducted; articles were screened using prespecified eligibility criteria. A standard risk of bias tool was used to evaluate studies. Mortality was extracted as the rate per 100 000 or the case fatality ratio (CFR; proportion of deaths among RSV/ACB cases). RESULTS: Among 42 included studies, 36 evaluated inpatient deaths; 10 used nationally representative populations updated through 2013, and only 2 included late-preterm/full-term otherwise healthy infants and children. The RSV/ACB definition varied across studies (multiple International Classification of Diseases [ICD] codes; laboratory confirmation); no study reported systematic testing for RSV. No studies reported RSV mortality rates, while 3 studies provided ACB mortality rates (0.57-9.4 per 100 000). CFRs ranged from 0% to 1.7% for RSV (n = 15) and from 0% to 0.17% for ACB (n = 6); higher CFRs were reported among premature, intensive care unit-admitted, and publicly insured infants and children. CONCLUSIONS: RSV mortality reported among US infants and children is variable. Current, nationally representative estimates are needed for otherwise healthy, late-preterm to full-term infants and children.

Systematic Literature Review of Respiratory Syncytial Virus Laboratory Testing Practices and Incidence in United States Infants and Children <5 Years of Age.

BACKGROUND: Respiratory syncytial virus (RSV) can cause serious illness in those aged <5 years in the United States, but uncertainty remains around which populations receive RSV testing. We conducted a systematic literature review of RSV testing patterns in studies published from 2000 to 2021. METHODS: Studies of RSV, medically attended RSV lower respiratory tract infections (LRTIs), and bronchiolitis were identified using standard methodology. Outcomes were clinical decisions to test for RSV, testing frequency, and testing incidence proportions in inpatient (IP), emergency department (ED), outpatient (OP), and urgent care settings. RESULTS: Eighty good-/fair-quality studies, which reported data from the period 1988-2020, were identified. Twenty-seven described the clinical decision to test, which varied across and within settings. Two studies reported RSV testing frequency for multiple settings, with higher testing proportions in IP (n = 2, range: 83%-85%, 1996-2009) compared with ED (n = 1, 25%, 2006-2009) and OP (n = 2, 15%-25%, 1996-2009). Higher RSV testing incidence proportions were observed among LRTI infant populations in the ED (n = 1, 74%, 2007-2008) and OP (n = 2, 54%-69%, 1995-2008). Incidence proportions in LRTI populations were not consistently higher in the IP setting (n = 13). Across studies and time, there was heterogeneity in RSV testing patterns, which may reflect varying detection methods, populations, locations, time periods, and healthcare settings. CONCLUSIONS: Not all infants and children with LRTI are tested for RSV, highlighting underestimation of RSV burden across all settings.

A Systematic Literature Review of the Burden of Respiratory Syncytial Virus and Health Care Utilization Among United States Infants Younger Than 1 Year.

BACKGROUND: The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized. METHODS: We systematically reviewed studies of RSV and bronchiolitis published 2000-2021 (data years, 1979-2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools. RESULTS: We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6-11 months in 2006 to 50.1 per 1000 per year among infants aged 0-2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0-22.7 per 1000 in 1997-1999 and 1997-2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non-high-risk infants in 1997-2012. CONCLUSIONS: Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.

Respiratory Syncytial Virus Is the Leading Cause of United States Infant Hospitalizations, 2009-2019: A Study of the National (Nationwide) Inpatient Sample.

BACKGROUND: This study describes leading causes of hospitalization, including respiratory syncytial virus (RSV), in United States infants (<1 year) from 2009 through 2019. METHODS: Within the National (Nationwide) Inpatient Sample (NIS) data, hospitalizations were determined by primary diagnosis using International Classification of Diseases, Ninth or Tenth Revision codes. RSV was defined as 079.6, 466.11, 480.1, B97.4, J12.1, J20.5, or J21.0. Bronchiolitis was defined as 466.19, J21.8, or J21.9. Leading causes overall and by sociodemographic variables were identified. The Kids' Inpatient Database (KID) was used for confirmatory analyses. RESULTS: Acute bronchiolitis due to RSV (code 466.11 or J21.0) was the leading primary diagnosis, accounting for 9.6% (95% confidence interval [CI], 9.4%-9.9%) and 9.3% (95% CI, 9.0%-9.6%) of total infant hospitalizations from January 2009 through September 2015 and October 2015 through December 2019, respectively; it was the leading primary diagnosis in every year accounting for >10% of total infant hospitalizations from December through March, reaching >15% in January-February. From 2009 through 2011, acute bronchiolitis due to RSV was the leading primary diagnosis in every birth month. Acute bronchiolitis due to RSV was the leading cause among all races/ethnicities, except Asian/Pacific Islanders, and all insurance payer groups. KID analyses confirmed these results. CONCLUSIONS: Acute bronchiolitis due to RSV is the leading cause of US infant hospitalizations.

Mortality Associated With Respiratory Syncytial Virus, Bronchiolitis, and Influenza Among Infants in the United States: A Birth Cohort Study From 1999 to 2018.

BACKGROUND: Infant mortality due to respiratory syncytial virus (RSV) in the United States is not well understood. METHODS: From 1999 to 2018, RSV, bronchiolitis, and influenza deaths were described for infants <1 year using linked birth/death datasets from the National Vital Statistics System. Mortality was described overall and by infant birth and death characteristics. Bronchiolitis was included as the plausible upper limit of RSV, while influenza served as a comparator. RESULTS: Total infant deaths were 561 RSV, 1603 bronchiolitis, and 504 influenza, and rates were 6.9 (95% confidence interval [CI], 6.4-7.5), 19.8 (95% CI, 18.9-20.8), and 6.2 (95% CI, 5.7-6.8) per 1 000 000 live births, respectively. The highest RSV rates were observed among <29 weeks' gestational age infants (103.5; 95% CI, 81.8-129.1), American Indian/Alaskan Native (20.3; 95% CI, 11.6-33.0), and Medicaid-insured (7.3; 95% CI, 5.9-8.9). However, RSV mortality burden was greatest in full-term (53.7%), white (44.9%), and Medicaid-insured (61.7%) infants. Deaths outside the inpatient setting were 21% and 54% for RSV and bronchiolitis; more Medicaid- (58%) and other/unknown-insured (69%) infants with bronchiolitis died outside of the inpatient setting, compared to privately insured infants (48%) (P = .0327). CONCLUSIONS: These national estimates emphasize the importance of considering all infants across all healthcare settings when describing RSV mortality.

Respiratory Syncytial Virus Burden and Healthcare Utilization in United States Infants <1 Year of Age: Study of Nationally Representative Databases, 2011-2019.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalizations in United States infants aged <1 year, but research has focused on select populations. METHODS: National (Nationwide) Inpatient Sample and National Emergency Department (ED) Sample data (2011-2019) were used to report RSV hospitalization (RSVH), bronchiolitis hospitalization (BH), and ED visit counts, percentage of total hospitalizations/visits, and rates per 1000 live births along with inpatient mortality, mechanical ventilation (MV), and total charges (2020 US dollars). RESULTS: Average annual RSVH and RSV ED visits were 56 927 (range, 43 845-66 155) and 131 999 (range, 89 809-177 680), respectively. RSVH rates remained constant over time (P = .5), whereas ED visit rates increased (P = .004). From 2011 through 2019, Medicaid infants had the highest average rates (RSVH: 22.3 [95% confidence interval {CI}, 21.5-23.1] per 1000; ED visits: 55.9 [95% CI, 52.4-59.4] per 1000) compared to infants with private or other/unknown insurance (RSVH: P < .0001; ED visits: P < .0001). From 2011 through 2019, for all races and ethnicities, Medicaid infants had higher average RSVH rates (up to 7 times) compared to infants with private or other/unknown insurance. RSVH mortality remained constant over time (P = .8), whereas MV use (2019: 13% of RSVH, P < .0001) and mean charge during hospitalization (2019: $21 513, P < .0001) increased. Bronchiolitis patterns were similar. CONCLUSIONS: This study highlights the importance of ensuring access to RSV preventive measures for all infants.

Interferon gamma expression and mortality in unselected cohorts of urothelial bladder cancer patients.

BACKGROUND: The role of interferon gamma (IFN-γ) expression in long-term survival has not been studied in patients with urinary bladder cancer (UBC). IFN-γ expression was characterized among various UBC patient cohorts to assess if IFN-γ status is associated with overall survival (OS). METHODS: A tumor-based IFN-γ gene signature was evaluated among adult UBC patients newly diagnosed between 2004 and 2017 from two hospital systems in New York. Patient cohorts included metastatic (stage IV or progressing to stage IV [MBC]), muscle-invasive (stages T2a to T4a [MIBC]), and non-muscle-invasive (carcinoma in situ or stages 0a, 0is, and I [NMIBC]) disease. Descriptive analyses were conducted comparing IFN-γ signature in the highest tertile to those in the lowest two tertiles. RESULTS: 234 patients with bladder cancer were evaluated (56 MBC, 38 MIBC, and 140 NMIBC). Median OS was only reached in the MIBC cohort for those with an IFN-γ signature in the lowest two tertiles (15.03 months [95% CI, 8.50-50.60]). Those with an IFN-γ signature in the highest tertile had a decreased risk of mortality in all cohorts indicating better survival, but this was statistically significant in only the MIBC cohort (adjusted HR = 0.09 [95% CI, 0.01-0.73]). CONCLUSION: IFN-γ signature status was associated with a decreased mortality risk in all cohorts, particularly MIBC, indicating that it may be a prognostic marker of survival in patients with UBC.

Theoretical attributable risk analysis and Disability Adjusted Life Years (DALYs) based on increased dairy consumption.

BACKGROUND: Identification of modifiable risk factors that may impact chronic disease risk is critical to public health. Our study objective was to conduct a theoretical population attributable risk analysis to estimate the burden of disease from low dairy intake and to estimate the impact of increased dairy intake on United States (US)-based disability adjusted life years (DALYs). METHODS: We conducted a comprehensive literature review to identify statistically significant summary relative risk estimates (SRREs) from recent meta-analyses of dairy consumption and key chronic disease outcomes. The SRREs were applied to preventive fractions using a range of categories (low to high) for population consumption of dairy products. The preventive fraction estimates were then applied to the number of DALYs for each health outcome in the US based on 2019 WHO estimates. The population attributable risk proportion estimates were calculated using the inverse of the SRRE from each meta-analysis using the same range of categories of consumption. These values were subsequently applied to the DALYs estimates to estimate the theoretical burden of disease attributable to low dairy intake. RESULTS: Statistically significant SRREs were identified in recent meta-analyses of total dairy consumption in relation to breast cancer, colorectal cancer, cardiovascular disease (CVD), type 2 diabetes (T2D), stroke, and hypertension. In this theoretical analysis, nearly 850,000 DALYs (or 5.0% of estimated years of healthy life lost) due to CVD and 200,000 DALYs (4.5%) due to T2D may be prevented by increased dairy consumption. Approximately 100,000 DALYs due to breast cancer (7.5%) and approximately 120,000 DALYs (8.5%) due to colorectal cancer may be prevented by high dairy intake. The numbers of DALYs for stroke and hypertension that may be prevented by increased dairy consumption were approximately 210,000 (6.0%) and 74,000 (5.5%), respectively. CONCLUSIONS: Consumption of dairy products has been associated with decreased risk of multiple chronic diseases of significant public health importance. The burden of disease that may potentially be prevented by increasing dairy consumption is substantial, and population-wide improvement in meeting recommended daily dairy intake goals could have a notable public health impact. However, this analysis is theoretical, and thus additional studies providing empirical evidence are needed to further clarify potential relationships between dairy intake and various health outcomes.