Assessment of associations between inhaled formaldehyde and lymphohematopoietic cancer through the integration of epidemiological and toxicological evidence with biological plausibility.

Formaldehyde is recognized as carcinogenic for the portal of entry sites, though conclusions are mixed regarding lymphohematopoietic (LHP) cancers. This systematic review assesses the likelihood of a causal relationship between formaldehyde and LHP cancers by integrating components recommended by NASEM. Four experimental rodent bioassays and 16 observational studies in humans were included following the implementation of the a priori protocol. All studies were assessed for risk of bias (RoB), and meta-analyses were conducted on epidemiological studies, followed by a structured assessment of causation based on GRADE and Bradford Hill. RoB analysis identified systemic limitations precluding confidence in the epidemiological evidence due to inadequate characterization of formaldehyde exposure and a failure to adequately adjust for confounders or effect modifiers, thus suggesting that effect estimates are likely to be impacted by systemic bias. Mixed findings were reported in individual studies; meta-analyses did not identify significant associations between formaldehyde inhalation (when measured as ever/never exposure) and LHP outcomes, with meta-SMRs ranging from 0.50 to 1.51, depending on LHP subtype. No associations with LHP-related lesions were reported in reliable animal bioassays. No biologically plausible explanation linking the inhalation of FA and LHP was identified, supported primarily by the lack of systemic distribution and in vivo genotoxicity. In conclusion, the inconsistent associations reported in a subset of the evidence were not considered causal when integrated with the totality of the epidemiological evidence, toxicological data, and considerations of biological plausibility. The impact of systemic biases identified herein could be quantitatively assessed to better inform causality and use in risk assessment.

From lab to life: Evaluating the reliability and validity of psychophysiological data from wearable devices in laboratory and ambulatory settings.

Despite the increasing popularity of ambulatory assessment, the reliability and validity of psychophysiological signals from wearable devices is unproven in daily life settings. We evaluated the reliability and validity of physiological signals (electrocardiogram, ECG; photoplethysmography, PPG; electrodermal activity, EDA) collected from two wearable devices (Movisens EcgMove4 and Empatica E4) in the lab (N = 67) and daily life (N = 20) among adults aged 18-64 with Mindware as the laboratory gold standard. Results revealed that both wearable devices' valid data rates in daily life were lower than in the laboratory (Movisens ECG 82.94 vs. 93.10%, Empatica PPG 8.79 vs. 26.14%, and Empatica EDA 41.16 vs. 42.67%, respectively). The poor valid data rates of Empatica PPG signals in the laboratory could be partially attributed to participants' hand movements (r = - .27, p = .03). In laboratory settings, heart rate (HR) derived from both wearable devices exhibited higher concurrent validity than heart rate variability (HRV) metrics (ICCs 0.98-1.00 vs. 0.75-0.97). The number of skin conductance responses (SCRs) derived from Empatica showed higher concurrent validity than skin conductance level (SCL, ICCs 0.38 vs. 0.09). Movisens EcgMove4 provided more reliable and valid HRV measurements than Empatica E4 in both laboratory (split-half reliability: 0.95-0.99 vs. 0.85-0.98; concurrent validity: 0.95-1.00 vs. 0.75-0.98; valid data rate: 93.10 vs. 26.14%) and ambulatory settings (split-half reliability: 0.99-1.00 vs. 0.89-0.98; valid data rate: 82.94 vs. 8.79%). Although the reliability and validity of wearable devices are improving, findings suggest researchers should select devices that yield consistently robust and valid data for their measures of interest.

The effect of bovine dairy products and their components on the incidence and natural history of infection: a systematic literature review.

BACKGROUND: Dairy products and their components may impact immune function, although the current evidence base has some research gaps. As part of a larger systematic literature review of dairy products/components (including probiotics, dairy proteins, and dairy fats) and immune function, we identified the available epidemiologic research on the impact of dairy products/components on incidence and natural history of infectious diseases. METHODS: PubMed and Embase databases were systematically searched through May 2022 to identify eligible studies using pre-defined Population, Intervention, Comparator, Outcomes, and Study design criteria. Herein, we focused on describing the impacts of dairy product/component on infectious disease outcomes, including the effect on leukocyte and cytokine response in humans. Risk of bias assessment was performed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. RESULTS: Among 9,832 studies identified from the larger literature search, 133 relevant publications from 128 studies reported on dairy product/component and infectious disease outcomes. Few studies are available on the impact of non-fermented milk and traditional yogurt on infectious disease. Evidence was identified to suggest milk and yogurt drinks fermented with Lactobacillus strains reduce the risk and burden of common infectious diseases (CIDs), although the findings are mixed and difficult to reconcile due to heterogenous study populations, bacterial strains, and study methods. Few studies are available on the impact of dairy products/components on the natural history of infection, with the available findings indicating probiotics may both improve gastrointestinal symptoms among HIV-infected persons and help eradicate and alleviate the symptoms of Heliobacter (H.) pylori. The available evidence also suggests lactoferrin may reduce the virological burden of COVID-19 and hepatitis C virus. No consistent changes in leukocytes or cytokine production were observed for any type of dairy product or their components, but probiotics appeared to enhance natural killer cell levels/activity and the phagocytic process. CONCLUSIONS: Dairy products, particularly those with added probiotics, may represent an easily accessible nutritional intervention to prevent and improve the course of infectious diseases. This review highlights the need for additional research in this potentially impactful area. PROSPERO REGISTRATION: CRD42022333780.

Daily Associations Between Sleep and Affect in Youth at Risk for Psychopathology: The Moderating Role of Externalizing Symptoms.

Problems with sleep, emotion regulation, and externalizing psychopathology are interrelated, but little is known about their day-to-day associations in youth. We examined self-reported daily sleep quality as a bidirectional predictor of next-day positive and negative affect (PA/NA), with externalizing symptoms as a moderator. Data were drawn from an ecological momentary assessment (EMA) study involving 82 youths (ages 9-13; 50% female; 44% White, 37% Black/African American) at high (n = 41) or low (n = 41) familial risk for psychopathology. Parents rated youths' externalizing symptoms at baseline. Youths then completed a 9-day EMA protocol, reporting sleep quality 1x/day and affect 4-8x/day. Daily means, peaks, and variability in PA and NA were computed. Multilevel models examined bidirectional associations between sleep and affect (between- and within-person), testing externalizing symptoms as a moderator and controlling for age and sex. In models of sleep predicting affect: Within-person, poorer-than-usual sleep quality predicted greater variability and higher peaks in next-day NA, but only for youth with higher levels of externalizing symptoms. Between-person, poor sleep quality and higher levels of externalizing symptoms predicted lower mean and peak PA. In models of affect predicting sleep: Within-person, lower-than-usual mean PA predicted poorer subsequent sleep quality, but only for youth with higher levels of externalizing symptoms. Between-person, youths with higher mean and peak PA had better sleep quality. These findings suggest that affective functioning is bidirectionally linked to daily self-reported sleep quality among high- and low-risk youth. Specific disturbances in daily sleep-affect cycles may be distinctly associated with externalizing psychopathology.

The Human Affectome.

Over the last decades, theoretical perspectives in the interdisciplinary field of the affective sciences have proliferated rather than converged due to differing assumptions about what human affective phenomena are and how they work. These metaphysical and mechanistic assumptions, shaped by academic context and values, have dictated affective constructs and operationalizations. However, an assumption about the purpose of affective phenomena can guide us to a common set of metaphysical and mechanistic assumptions. In this capstone paper, we home in on a nested teleological principle for human affective phenomena in order to synthesize metaphysical and mechanistic assumptions. Under this framework, human affective phenomena can collectively be considered algorithms that either adjust based on the human comfort zone (affective concerns) or monitor those adaptive processes (affective features). This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope the Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.

Long-term stability of respiratory sinus arrhythmia among adults with and without a history of depression.

Respiratory sinus arrhythmia (RSA) is an index of parasympathetic nervous system activity reflecting respiratory influences on heart rate. This influence is typically measured as high frequency heart rate variability (HF-HRV) or root mean square of successive differences (RMSSD) of adjacent inter-beat intervals. Examining the long-term stability of its measurement is important as levels of resting RSA have been conceptualized as a marker of individual differences; in particular, of an individual's autonomic regulation and affect-related processes, including emotion regulation. At present, it is not known if resting RSA levels reflect stable differences over a long-term period (i.e., >1 year). Even less is known about how RSA stability differs as a function of depression history and whether it relates to depression risk trajectories. In the present study, we examined the 1.5-year test-retest reliability of resting RSA using the intraclass correlation coefficient (ICC) in 82 adults: n = 41 with a history of depression (ever-depressed); n = 41 controls with no depression history (never-depressed). HF-HRV was fairly stable in both groups (ever-depressed ICC = 0.55, never-depressed ICC = 0.54). RMSSD was also fairly stable in ever-depressed adults (ICC = 0.57) and never-depressed controls (ICC = 0.40). ICC values for both indices did not differ between groups per overlapping 95% confidence intervals. Therefore, RSA stability as assessed by both frequency (HF-HRV) and time domain (RMSSD) measures was not attenuated by a depression history. Implications and the need for future research are discussed.

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.

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.

Skills program for awareness, connectedness, and empowerment: A conceptual framework of a skills group for individuals with a psychosis-risk syndrome.

Intervention strategies for those diagnosed with psychotic disorders such as schizophrenia can be effective in reducing symptoms and improving quality of life. While strides have been made in developing prevention and intervention strategies earlier on in the disease progression, among those at clinical high-risk (CHR) for psychosis, challenges with heterogeneity can limit symptom and diagnosis specific treatment. Here, we discuss a newly developed therapy skills group called the Skills Program for Awareness, Connectedness, and Empowerment (SPACE) that integrates different types of behavioral skills - standard and radically open dialectical behavioral therapy as well as cognitive behavioral therapy - for CHR youth between the ages of 13-18 years. With the diathesis-stress framework serving as a foundation, the intervention is divided into three stages. These stages target specific signs and symptoms contributing to the progression of CHR symptoms. Stage 1 targets stress (with the goal of developing awareness and reducing distress), stage 2 targets self-disturbances (with a goal of increasing self-connectedness), and stage 3 targets social connectedness (with a goal of improving social domains of functioning). The focus of this article is to introduce the theoretical framework underlying the pilot skills group and discuss ongoing progress. Clinical Trial Registration: NCT05398120; https://clinicaltrials.gov/ct2/show/NCT05398120.

Randomized trial of brief interpersonal psychotherapy and cognitive behavioral therapy for depression delivered both in-person and by telehealth.

BACKGROUND: Expert consensus guidelines recommend Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT), interventions that were historically delivered face-to-face, as first-line treatments for Major Depressive Disorder (MDD). Despite the ubiquity of telehealth following the COVID-19 pandemic, little is known about differential outcomes with CBT versus IPT delivered in-person (IP) or via telehealth (TH) or whether working alliance is affected. METHODS: Adults meeting DSM-5 criteria for MDD were randomly assigned to either 8 sessions of IPT or CBT (group). Mid-trial, COVID-19 forced a change of therapy delivery from IP to TH (study phase). We compared changes in Hamilton Rating Scale for Depression (HRSD-17) and Working Alliance Inventory (WAI) scores for individuals by group and phase: CBT-IP (n = 24), CBT-TH (n = 11), IPT-IP (n = 25) and IPT-TH (n = 17). RESULTS: HRSD-17 scores declined significantly from pre to post treatment (pre: M = 17.7, SD = 4.4 vs. post: M = 11.7, SD = 5.9; p < .001; d = 1.45) without significant group or phase effects. WAI scores did not differ by group or phase. Number of completed therapy sessions was greater for TH (M = 7.8, SD = 1.2) relative to IP (M = 7.2, SD = 1.6) (Mann-Whitney U = 387.50, z = -2.24, p = .025). LIMITATIONS: Participants were not randomly assigned to IP versus TH. Sample size is small. CONCLUSIONS: This study provides preliminary evidence supporting the efficacy of both brief IPT and CBT, delivered by either TH or IP, for depression. It showed that working alliance is preserved in TH, and delivery via TH may improve therapy adherence. Prospective, randomized controlled trials are needed to definitively test efficacy of brief IPT and CBT delivered via TH versus IP.

Economic Choice and Heart Rate Fractal Scaling Indicate That Cognitive Effort Is Reduced by Depression and Boosted by Sad Mood.

BACKGROUND: People with depression typically exhibit diminished cognitive control. Control is subjectively costly, prompting speculation that control deficits reflect reduced cognitive effort. Evidence that people with depression exert less cognitive effort is mixed, however, and motivation may depend on state affect. METHODS: We used a cognitive effort discounting task to measure propensity to expend cognitive effort and fractal structure in the temporal dynamics of interbeat intervals to assess on-task effort exertion for 49 healthy control subjects, 36 people with current depression, and 67 people with remitted depression. RESULTS: People with depression discounted more steeply, indicating that they were less willing to exert cognitive effort than people with remitted depression and never-depressed control subjects. Also, steeper discounting predicted worse functioning in daily life. Surprisingly, a sad mood induction selectively boosted motivation among participants with depression, erasing differences between them and control subjects. During task performance, depressed participants with the lowest cognitive motivation showed blunted autonomic reactivity as a function of load. CONCLUSIONS: Discounting patterns supported the hypothesis that people with current depression would be less willing to exert cognitive effort, and steeper discounting predicted lower global functioning in daily life. Heart rate fractal scaling proved to be a highly sensitive index of cognitive load, and data implied that people with lower motivation for cognitive effort had a diminished physiological capacity to respond to rising cognitive demands. State affect appeared to influence motivation among people with current depression given that they were more willing to exert cognitive effort following a sad mood induction.

The late positive potential during affective picture processing: Associations with daily life emotional functioning among adolescents with anxiety disorders.

Pediatric anxiety disorders are characterized by potentiated threat responses and maladaptive emotion regulation (ER). The Late Positive Potential (LPP) is a neural index of heightened attention to emotional stimuli. Anxious individuals typically exhibit a larger LPP to unpleasant stimuli, but the LPP may also be blunted to unpleasant and pleasant stimuli for those with co-morbid depression. While a larger LPP is thought to reflect greater emotional reactivity, it is unknown to what extent variation in the LPP to laboratory stimuli corresponds to daily emotional functioning. We assessed the LPP in the laboratory in response to unpleasant, pleasant, and neutral images in combination with ecological momentary assessment of emotional reactivity and regulation in daily life among youth (9-14 years old; 55 % female) with anxiety disorders (ANX, N = 130) and no psychiatric diagnoses (ND, N = 47). We tested whether LPP amplitudes to unpleasant and pleasant stimuli (vs. neutral) are greater in ANX (vs. ND) youth and whether LPP amplitudes inversely correlate with co-morbid depression symptoms. We also examined associations between the LPP and daily life emotional functioning among ANX and ND youth. We found no group-by-valence effects on LPP amplitudes. Within ANX youth, higher depression symptoms were associated with smaller LPP amplitudes to unpleasant, but not pleasant, stimuli relative to neutral stimuli. Larger LPP amplitudes to emotional (relative to neutral) stimuli were correlated with use of specific ER strategies among ANX and ND youth but not emotional reactivity. While the LPP may reflect initial emotional reactivity to laboratory stimuli, it is associated with ER behaviors, and not emotional reactivity, in daily life.

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.

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.