Evaluating Acute Viral Gastroenteritis Severity: Modified Vesikari and Clark Scoring Systems.

OBJECTIVE: Acute gastroenteritis (AGE) is the second leading cause of death in children worldwide. Objectively evaluating disease severity is critical for assessing future interventions. We used data from a large, prospective surveillance study to assess risk factors associated with severe presentation using modified Vesikari score (MVS) and Clark score (CS) of severity. METHODS: From December 1, 2012 to June 30, 2016, AGE surveillance was performed for children between 15 days and 17 years old in the emergency, inpatient, and outpatient settings at Vanderbilt's Monroe Carell Jr. Children's Hospital in Nashville, TN. Stool specimens were tested for norovirus, sapovirus, rotavirus, and astrovirus. We compared demographic and clinical characteristics, along with the MVS and CS, by viral detection status and by setting. RESULTS: Of the 6309 eligible children, 4216 (67%) were enrolled, with 3256 (77%) providing a stool specimen. The median age was 1.9 years, 52% were male, and 1387 (43%) of the stool samples were virus positive. Younger age, male sex, hospitalization, and rotavirus detection were significantly associated with higher mean MVS and CS. Non-Hispanic Black race and ethnicity was associated with a lower mean MVS and CS as compared with non-Hispanic white race and ethnicity. Prematurity and enrollment in the ED were associated with higher mean CS. The 2 scoring systems were highly correlated. CONCLUSIONS: Rotavirus continues to be associated with more severe pediatric illness compared with other viral causes of AGE. MVS and CS systems yielded comparable results and can be useful tools to assess AGE severity.

Accuracy of Influenza ICD-10 Diagnosis Codes in Identifying Influenza Illness in Children.

Importance: Studies of influenza in children commonly rely on coded diagnoses, yet the ability of International Classification of Diseases, Ninth Revision codes to identify influenza in the emergency department (ED) and hospital is highly variable. The accuracy of newer International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes to identify influenza in children is unknown. Objective: To determine the accuracy of ICD-10 influenza discharge diagnosis codes in the pediatric ED and inpatient settings. Design, Setting, and Participants: Children younger than 18 years presenting to the ED or inpatient settings with fever and/or respiratory symptoms at 7 US pediatric medical centers affiliated with the Centers for Disease Control and Prevention-sponsored New Vaccine Surveillance Network from December 1, 2016, to March 31, 2020, were included in this cohort study. Nasal and/or throat swabs were collected for research molecular testing for influenza, regardless of clinical testing. Data, including ICD-10 discharge diagnoses and clinical testing for influenza, were obtained through medical record review. Data analysis was performed in August 2023. Main Outcomes and Measures: The accuracy of ICD-10-coded discharge diagnoses was characterized using molecular clinical or research laboratory test results as reference. Measures included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Estimates were stratified by setting (ED vs inpatient) and age (0-1, 2-4, and 5-17 years). Results: A total of 16 867 children in the ED (median [IQR] age, 2.0 [0.0-4.0] years; 9304 boys [55.2%]) and 17 060 inpatients (median [IQR] age, 1.0 [0.0-4.0] years; 9798 boys [57.4%]) were included. In the ED, ICD-10 influenza diagnoses were highly specific (98.0%; 95% CI, 97.8%-98.3%), with high PPV (88.6%; 95% CI, 88.0%-89.2%) and high NPV (85.9%; 95% CI, 85.3%-86.6%), but sensitivity was lower (48.6%; 95% CI, 47.6%-49.5%). Among inpatients, specificity was 98.2% (95% CI, 98.0%-98.5%), PPV was 82.8% (95% CI, 82.1%-83.5%), sensitivity was 70.7% (95% CI, 69.8%-71.5%), and NPV was 96.5% (95% CI, 96.2%-96.9%). Accuracy of ICD-10 diagnoses varied by patient age, influenza season definition, time between disease onset and testing, and clinical setting. Conclusions and Relevance: In this large cohort study, influenza ICD-10 discharge diagnoses were highly specific but moderately sensitive in identifying laboratory-confirmed influenza; the accuracy of influenza diagnoses varied by clinical and epidemiological factors. In the ED and inpatient settings, an ICD-10 diagnosis likely represents a true-positive influenza case.

The Goldilocks Dilemma on Balancing User Response and Reflection in mHealth Interventions: Observational Study.

Background: Mobile health (mHealth) has the potential to radically improve health behaviors and quality of life; however, there are still key gaps in understanding how to optimize mHealth engagement. Most engagement research reports only on system use without consideration of whether the user is reflecting on the content cognitively. Although interactions with mHealth are critical, cognitive investment may also be important for meaningful behavior change. Notably, content that is designed to request too much reflection could result in users' disengagement. Understanding how to strike the balance between response burden and reflection burden has critical implications for achieving effective engagement to impact intended outcomes. Objective: In this observational study, we sought to understand the interplay between response burden and reflection burden and how they impact mHealth engagement. Specifically, we explored how varying the response and reflection burdens of mHealth content would impact users' text message response rates in an mHealth intervention. Methods: We recruited support persons of people with diabetes for a randomized controlled trial that evaluated an mHealth intervention for diabetes management. Support person participants assigned to the intervention (n=148) completed a survey and received text messages for 9 months. During the 2-year randomized controlled trial, we sent 4 versions of a weekly, two-way text message that varied in both reflection burden (level of cognitive reflection requested relative to that of other messages) and response burden (level of information requested for the response relative to that of other messages). We quantified engagement by using participant-level response rates. We compared the odds of responding to each text and used Poisson regression to estimate associations between participant characteristics and response rates. Results: The texts requesting the most reflection had the lowest response rates regardless of response burden (high reflection and low response burdens: median 10%, IQR 0%-40%; high reflection and high response burdens: median 23%, IQR 0%-51%). The response rate was highest for the text requesting the least reflection (low reflection and low response burdens: median 90%, IQR 61%-100%) yet still relatively high for the text requesting medium reflection (medium reflection and low response burdens: median 75%, IQR 38%-96%). Lower odds of responding were associated with higher reflection burden (P<.001). Younger participants and participants who had a lower socioeconomic status had lower response rates to texts with more reflection burden, relative to those of their counterparts (all P values were <.05). Conclusions: As reflection burden increased, engagement decreased, and we found more disparities in engagement across participants' characteristics. Content encouraging moderate levels of reflection may be ideal for achieving both cognitive investment and system use. Our findings provide insights into mHealth design and the optimization of both engagement and effectiveness.

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients.

ABSTRACT: Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B- and T-cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over 3 influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and prevaccination to postvaccination geometric mean fold rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination inhibition antibody titers (28-42 days, and ∼6 months after 2 doses). For cell subpopulations identified as predictive of a response to all 3 antigens, we conducted a sensitivity analysis including time after transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations; 7 significantly predicted responses to all 3 antigens 28 to 42 days after a 2-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of posttransplant vaccine administration. In conclusion, several B- and T-cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.

Seasonality, Clinical Characteristics, and Outcomes of Respiratory Syncytial Virus Disease by Subtype Among Children Aged <5 Years: New Vaccine Surveillance Network, United States, 2016-2020.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. METHODS: During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. RESULTS: Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. CONCLUSIONS: Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.

Prescription Opioid Exposure During Pregnancy and Risk of Spontaneous Preterm Delivery.

Importance: Opioid exposure during pregnancy has been associated with preterm birth, but prior studies have not differentiated between spontaneous and indicated preterm birth or fully investigated these associations as functions of opioid dose. Objective: To determine whether prescription opioid use during pregnancy is associated with spontaneous preterm birth and whether the association is dose-dependent. Design, Setting, and Participants: This case-control study examined a retrospective cohort of pregnant patients enrolled in Tennessee Medicaid. Enrollment files were linked to health care encounters, hospital discharge information, birth certificate data, and prescription fills. Eligible participants were pregnant people ages 15 to 44 years without opioid use disorder who experienced birth of a single fetus at 24 weeks gestation or greater between 2007 and 2019 with linked birth certificate data. Cases of spontaneous preterm birth were matched with up to 10 controls based on pregnancy start date, race, ethnicity, age at delivery within 2 years, and history of prior preterm birth. Cases and matched controls were continuously enrolled in TennCare for at least 90 days prior to the index date (case delivery date). Exposure: Total opioid MME filled during the 60 days prior to the index date. Main Outcomes and Measures: The primary outcome was spontaneous preterm birth determined by a validated algorithm using birth certificate data. Conditional logistic regression was used to estimate the association between spontaneous preterm birth and total opioid morphine milligram equivalents (MME) dispensed, adjusting for parity, prepregnancy body mass index, education level, tobacco use, hepatitis infections, and pain indications. Results: A total of 25 391 cases (median [IQR] age, 23 [20-28] years; 127 Asian [0.5%], 9820 Black [38.7%], 664 Hispanic [2.6%]; 14 748 non-Hispanic White [58.1%]) with spontaneous preterm birth were identified and matched with 225 696 controls (median [IQR] age, 23 [20-27] years; 229 Asian [0.1%], 89 819 Black [39.8%], 3590 Hispanic [1.6%]; 132 002 non-Hispanic White [58.5%]) (251 087 patients total), with 18 702 patients (7.4%) filling an opioid prescription in the 60 days prior to the index date. Each doubling of nonzero opioid MME was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure (adjusted odds ratio, 1.04; 95% CI, 1.01-1.08). Conclusions and Relevance: In this case-control study, a positive association was found between total prescription opioid dose dispensed and the odds of spontaneous preterm birth. These findings support guidance to minimize opioid exposure during pregnancy and prescribe the lowest dose necessary.

Clinical prediction model: Multisystem inflammatory syndrome in children versus Kawasaki disease.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious complication of severe acute respiratory syndrome coronavirus 2 infection. Features of MIS-C overlap with those of Kawasaki disease (KD). OBJECTIVE: The study objective was to develop a prediction model to assist with this diagnostic dilemma. METHODS: Data from a retrospective cohort of children hospitalized with KD before the coronavirus disease 2019 pandemic were compared to a prospective cohort of children hospitalized with MIS-C. A bootstrapped backwards selection process was used to develop a logistic regression model predicting the probability of MIS-C diagnosis. A nomogram was created for application to individual patients. RESULTS: Compared to children with incomplete and complete KD (N = 602), children with MIS-C (N = 105) were older and had longer hospitalizations; more frequent intensive care unit admissions and vasopressor use; lower white blood cell count, lymphocyte count, erythrocyte sedimentation rate, platelet count, sodium, and alanine aminotransferase; and higher hemoglobin and C-reactive protein (CRP) at admission. Left ventricular dysfunction was more frequent in patients with MIS-C, whereas coronary abnormalities were more common in those with KD. The final prediction model included age, sodium, platelet count, alanine aminotransferase, reduction in left ventricular ejection fraction, and CRP. The model exhibited good discrimination with AUC 0.96 (95% confidence interval: [0.94-0.98]) and was well calibrated (optimism-corrected intercept of -0.020 and slope of 0.99). CONCLUSIONS: A diagnostic prediction model utilizing admission information provides excellent discrimination between MIS-C and KD. This model may be useful for diagnosis of MIS-C but requires external validation.

The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

Glycemic outcomes of a family-focused intervention for adults with type 2 diabetes: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

AIMS: Family/friend Activation to Motivate Self-care (FAMS) is a self-care support intervention delivered via mobile phones. We evaluated FAMS' effects on hemoglobin A1c (HbA1c) and intervention targets among adults with type 2 diabetes in a 15-month RCT. METHODS: Persons with diabetes (PWDs) were randomized to FAMS or control with their support person (family/friend, optional). FAMS included monthly phone coaching and text messages for PWDs, and text messages for support persons over a 9-month intervention period. RESULTS: PWDs (N = 329) were 52 % male, 39 % reported minoritized race or ethnicity, with mean HbA1c 8.6 ± 1.7 %. FAMS improved HbA1c among PWDs with a non-cohabitating support person (-0.64 %; 95 % CI [-1.22 %, -0.05 %]), but overall mean effects were not significant. FAMS improved intervention targets including self-efficacy, dietary behavior, and family/friend involvement during the intervention period; these improvements mediated post-intervention HbA1c improvements (total indirect effect -0.27 %; 95 % CI [-0.49 %, -0.09 %]) and sustained HbA1c improvements at 12 months (total indirect effect -0.19 %; 95 % CI [-0.40 %, -0.01 %]). CONCLUSIONS: Despite improvements in most intervention targets, HbA1c improved only among PWDs engaging non-cohabitating support persons suggesting future family interventions should emphasize inclusion of these relationships. Future work should also seek to identify intervention targets that mediate improvements in HbA1c.

Well-being outcomes of a family-focused intervention for persons with type 2 diabetes and support persons: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

Aims: Type 2 diabetes self-management occurs within social contexts. We sought to test the effects of Family/friends Activation to Motivate Self-care (FAMS), a self-care support intervention delivered via mobile phones, on psychosocial outcomes for persons with diabetes (PWDs) and their support persons. Methods: PWDs had the option to enroll with a friend/family member as a support person in a 15-month RCT to evaluate FAMS versus enhanced usual care. FAMS included 9-months of monthly phone coaching and text message support for PWDs, and text message support for enrolled support persons. Results: PWDs (N=329) were 52% male and 39% from minoritized racial or ethnic groups; 50% enrolled with elevated diabetes distress. Support persons (N=294) were 26% male and 33% minoritized racial or ethnic groups. FAMS improved PWDs' diabetes distress ( d =-0.19) and global well-being ( d =0.21) during the intervention, with patterns of larger effects among minoritized groups. Post-intervention and sustained (15-month) improvements were driven by changes in PWDs' self-efficacy, self-care behaviors, and autonomy support. Among support persons, FAMS improved helpful involvement without increasing burden or harmful involvement. Conclusions: FAMS improved PWDs' psychosocial well-being, with post-intervention and sustained improvements driven by improved self-efficacy, self-care, and autonomy support. Support persons increased helpful involvement without adverse effects.

Glycemic outcomes of a family-focused intervention for adults with type 2 diabetes: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

Aims: Family/friends Activation to Motivate Self-care (FAMS) is a self-care support intervention delivered via mobile phones. We evaluated FAMS effects on hemoglobin A1c (HbA1c) and intervention targets among adults with type 2 diabetes in a 15-month RCT. Methods: Persons with diabetes (PWDs) and their support persons (family/friend, optional) were randomized to FAMS or control. FAMS included monthly phone coaching and text messages for PWDs, and text messages for support persons over a 9-month intervention period. Results: PWDs (N=329) were 52% male, 39% from minoritized racial or ethnic groups, with mean HbA1c 8.6±1.7%. FAMS improved HbA1c among PWDs with a non-cohabitating support person (-0.64%; 95% CI [-1.22%, -0.05%]), but overall effects were not significant. FAMS improved intervention targets including self-efficacy, dietary behavior, and family/friend involvement during the intervention period; these improvements mediated post-intervention HbA1c improvements (total indirect effect -0.27%; 95% CI [-0.49%, -0.09%]) and sustained HbA1c improvements at 12 months (total indirect effect -0.19%; 95% CI [-0.40%, -0.01%]). Conclusions: Despite improvements in most intervention targets, HbA1c improved only among PWDs engaging non-cohabitating support persons suggesting future family interventions should emphasize inclusion of these relationships. Future work should also seek to identify intervention targets that mediate improvements in HbA1c.

Well-being outcomes of a family-focused intervention for persons with type 2 diabetes and support persons: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

AIMS: Type 2 diabetes self-management occurs within social contexts. We sought to test the effects of Family/friend Activation to Motivate Self-care (FAMS), a self-care support intervention delivered via mobile phones, on psychosocial outcomes for persons with diabetes (PWDs) and their support persons. METHODS: PWDs had the option to enroll with a friend/family member as a support person in a 15-month RCT to evaluate FAMS versus enhanced usual care. FAMS included 9 months of monthly phone coaching and text message support for PWDs, and text message support for enrolled support persons. RESULTS: PWDs (N = 329) were 52% male and 39% reported minoritized race or ethnicity ; 50% enrolled with elevated diabetes distress. Support persons (N = 294) were 26% male and 33% reported minoritized race or ethnicity. FAMS improved PWDs' diabetes distress (d = -0.19) and global well-being (d = 0.21) during the intervention, with patterns of larger effects among minoritized groups. Post-intervention (9-month) and sustained (15-month) improvements were driven by changes in PWDs' self-efficacy, self-care behaviors, and autonomy support. Among support persons, FAMS improved helpful involvement without increasing burden or harmful involvement. CONCLUSIONS: FAMS improved PWDs' psychosocial well-being, with post-intervention and sustained improvements driven by improved self-efficacy, self-care, and autonomy support. Support persons increased helpful involvement without adverse effects.

Family Typology for Adults With Type 2 Diabetes: Longitudinal Stability and Validity for Diabetes Management and Well-being.

OBJECTIVE: We validated longitudinally a typology of diabetes-specific family functioning (named Collaborative and Helpful, Satisfied with Low Involvement, Want More Involvement, and Critically Involved) in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted k-means cluster analyses with nine dimensions to determine if the typology replicated in a diverse sample and if type assignment was robust to variations in sampling and included dimensions. In a subsample with repeated assessments over 9 months, we examined the stability and validity of the typology. We also applied a multinomial logistic regression approach to make the typology usable at the individual level, like a diagnostic tool. RESULTS: Participants (N = 717) were 51% male, more than one-third reported minority race or ethnicity, mean age was 57 years, and mean hemoglobin A1c (HbA1c) was 7.9% (63 mmol/mol; 8.7% [72 mmol/mol] for the longitudinal subsample). The typology was replicated with respect to the number of types and dimension patterns. Type assignment was robust to sampling variations (97% consistent across simulations). Type had an average 52% stability over time within participants; instability was not explained by measurement error. Over 9 months, type was independently associated with HbA1c, diabetes self-efficacy, diabetes medication adherence, diabetes distress, and depressive symptoms (all P < 0.05). CONCLUSIONS: The typology of diabetes-specific family functioning was replicated, and longitudinal analyses suggest type is more of a dynamic state than a stable trait. However, type varies with diabetes self-management and well-being over time as a consistent independent indicator of outcomes. The typology is ready to be applied to further precision medicine approaches to behavioral and psychosocial diabetes research and care.

Maternal Opioid Use Disorder and the Risk of Postneonatal Infant Mortality.

Importance: The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS). Objective: To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD. Design, Setting, and Participants: The study team conducted a retrospective cohort study of 390 075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023. Exposure: Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed). Main Outcome and Measures: The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death. Results: Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375 718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65). Conclusions and Relevance: Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.

Family involvement and diabetes distress across dyads for adults with type 2 diabetes.

OBJECTIVE: Family/friend involvement and diabetes distress are associated with outcomes for persons with type 2 diabetes (PWDs), but little is known about how they relate to each other. We aim to (1) describe associations between PWD and support person (SP) distress; (2) describe associations between involvement and diabetes distress for PWDs, for SPs, and across the dyad; and (3) explore whether associations differ by PWD-SP cohabitation. METHODS: PWDs and SPs co-enrolled in a study evaluating the effects of a self-care support intervention and completed self-report measures at baseline. RESULTS: PWDs and SPs (N = 297 dyads) were, on average, in their mid-50s and around one-third identified as racial or ethnic minorities. The association between PWD and SP diabetes distress was small (Spearman's ρ = 0.25, p < 0.01). For PWDs, experienced harmful involvement from family/friends was associated with more diabetes distress (standardized ß = 0.23, p < 0.001) independent of helpful involvement in adjusted models. Separately, SPs' self-reported harmful involvement was associated with their own diabetes distress (standardized ß = 0.35, p < 0.001) and with PWDs' diabetes distress (standardized ß = 0.25, p = 0.002), independent of SPs' self-reported helpful involvement. CONCLUSION AND PRACTICE IMPLICATIONS: Findings suggest dyadic interventions may need to address both SP harmful involvement and SP diabetes distress, in addition to PWD distress.

Clinical characteristics and outcomes of children with single or co-detected rhinovirus-associated acute respiratory infection in Middle Tennessee.

BACKGROUND: Rhinovirus (RV) is one of the most common etiologic agents of acute respiratory infection (ARI), which is a leading cause of morbidity and mortality in young children. The clinical significance of RV co-detection with other respiratory viruses, including respiratory syncytial virus (RSV), remains unclear. We aimed to compare the clinical characteristics and outcomes of children with ARI-associated RV-only detection and those with RV co-detection-with an emphasis on RV/RSV co-detection. METHODS: We conducted a prospective viral surveillance study (11/2015-7/2016) in Nashville, Tennessee. Children < 18 years old who presented to the emergency department (ED) or were hospitalized with fever and/or respiratory symptoms of < 14 days duration were eligible if they resided in one of nine counties in Middle Tennessee. Demographics and clinical characteristics were collected by parental interviews and medical chart abstractions. Nasal and/or throat specimens were collected and tested for RV, RSV, metapneumovirus, adenovirus, parainfluenza 1-4, and influenza A-C using reverse transcription quantitative polymerase chain reaction assays. We compared the clinical characteristics and outcomes of children with RV-only detection and those with RV co-detection using Pearson's χ2 test for categorical variables and the two-sample t-test with unequal variances for continuous variables. RESULTS: Of 1250 children, 904 (72.3%) were virus-positive. RV was the most common virus (n = 406; 44.9%), followed by RSV (n = 207; 19.3%). Of 406 children with RV, 289 (71.2%) had RV-only detection, and 117 (28.8%) had RV co-detection. The most common virus co-detected with RV was RSV (n = 43; 36.8%). Children with RV co-detection were less likely than those with RV-only detection to be diagnosed with asthma or reactive airway disease both in the ED and in-hospital. We did not identify differences in hospitalization, intensive care unit admission, supplemental oxygen use, or length of stay between children with RV-only detection and those with RV co-detection. CONCLUSION: We found no evidence that RV co-detection was associated with poorer outcomes. However, the clinical significance of RV co-detection is heterogeneous and varies by virus pair and age group. Future studies of RV co-detection should incorporate analyses of RV/non-RV pairs and include age as a key covariate of RV contribution to clinical manifestations and infection outcomes.

Incidence of and risk factors for influenza-associated hospital encounters in pediatric solid organ transplant recipients.

Few studies have defined the incidence of and risk factors for influenza infection in pediatric solid organ transplant (SOT) recipients. We used a linkage between the Pediatric Health Information System and the Scientific Registry of Transplant Recipients databases to identify posttransplant influenza-associated hospital encounters (IAHEs) in pediatric SOT recipients of single-organ transplants. Among 7997 unique pediatric SOT recipients transplanted between January 01, 2006, and January 06, 2016, estimated 1- and 3-year posttransplant cumulative incidence rates of IAHEs were 2.7% (95% CI, 2.4%-3.1%) and 7.4% (95% CI, 6.8%-8.0%), respectively. One- and 3-year cumulative incidence rates of severe IAHEs were 0.3% (95% CI, 0.2%-0.5%) and 0.9% (95% CI, 0.7%-1.2%), respectively. Multivariable analysis showed that the organ type (adjusted subdistribution hazard ratio [aSHR]-kidney: reference, liver: 0.64 [95% CI, 0.49-0.84], and heart: 0.72 [95% CI, 0.57-0.93]), race/ethnicity (aSHR-non-Hispanic White: reference, non-Hispanic Black: 1.63 [95% CI, 1.29-2.07], Hispanic 1.57 [95% CI, 1.27-1.94]), and increasing age at transplant (aSHR, 0.93 [95% CI, 0.91-0.94]) were significantly associated with IAHE occurrence. Heart transplant recipients had a near statistically significant increase in hazard for severe IAHE (aSHR 1.96 [0.92-3.49]). Our findings may help guide future influenza prevention efforts and facilitate intervention impact assessment measurement in pediatric SOT recipients.

Circulation of Rhinoviruses and/or Enteroviruses in Pediatric Patients With Acute Respiratory Illness Before and During the COVID-19 Pandemic in the US.

Importance: Rhinoviruses and/or enteroviruses, which continued to circulate during the COVID-19 pandemic, are commonly detected in pediatric patients with acute respiratory illness (ARI). Yet detailed characterization of rhinovirus and/or enterovirus detection over time is limited, especially by age group and health care setting. Objective: To quantify and characterize rhinovirus and/or enterovirus detection before and during the COVID-19 pandemic among children and adolescents seeking medical care for ARI at emergency departments (EDs) or hospitals. Design, Setting, and Participants: This cross-sectional study used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective surveillance platform, for pediatric patients who sought medical care for fever and/or respiratory symptoms at 7 EDs or hospitals within NVSN across the US between December 2016 and February 2021. Persons younger than 18 years were enrolled in NVSN, and respiratory specimens were collected and tested for multiple viruses. Main Outcomes and Measures: Proportion of patients in whom rhinovirus and/or enterovirus, or another virus, was detected by calendar month and by prepandemic (December 1, 2016, to March 11, 2020) or pandemic (March 12, 2020, to February 28, 2021) periods. Month-specific adjusted odds ratios (aORs) for rhinovirus and/or enterovirus-positive test results (among all tested) by setting (ED or inpatient) and age group (<2, 2-4, or 5-17 years) were calculated, comparing each month during the pandemic to equivalent months of previous years. Results: Of the 38 198 children and adolescents who were enrolled and tested, 11 303 (29.6%; mean [SD] age, 2.8 [3.7] years; 6733 boys [59.6%]) had rhinovirus and/or enterovirus-positive test results. In prepandemic and pandemic periods, rhinoviruses and/or enteroviruses were detected in 29.4% (9795 of 33 317) and 30.9% (1508 of 4881) of all patients who were enrolled and tested and in 42.2% (9795 of 23 236) and 73.0% (1508 of 2066) of those with test positivity for any virus, respectively. Rhinoviruses and/or enteroviruses were the most frequently detected viruses in both periods and all age groups in the ED and inpatient setting. From April to September 2020 (pandemic period), rhinoviruses and/or enteroviruses were detectable at similar or lower odds than in prepandemic years, with aORs ranging from 0.08 (95% CI, 0.04-0.19) to 0.76 (95% CI, 0.55-1.05) in the ED and 0.04 (95% CI, 0.01-0.11) to 0.71 (95% CI, 0.47-1.07) in the inpatient setting. However, unlike some other viruses, rhinoviruses and/or enteroviruses soon returned to prepandemic levels and from October 2020 to February 2021 were detected at similar or higher odds than in prepandemic months in both settings, with aORs ranging from 1.47 (95% CI, 1.12-1.93) to 3.01 (95% CI, 2.30-3.94) in the ED and 1.36 (95% CI, 1.03-1.79) to 2.44 (95% CI, 1.78-3.34) in the inpatient setting, and in all age groups. Compared with prepandemic years, during the pandemic, rhinoviruses and/or enteroviruses were detected in patients who were slightly older, although most (74.5% [1124 of 1508]) were younger than 5 years. Conclusions and Relevance: Results of this study show that rhinoviruses and/or enteroviruses persisted and were the most common respiratory virus group detected across all pediatric age groups and in both ED and inpatient settings. Rhinoviruses and/or enteroviruses remain a leading factor in ARI health care burden, and active ARI surveillance in children and adolescents remains critical for defining the health care burden of respiratory viruses.

Social Vulnerability and Initiation of Pharmacotherapy for Gestational Diabetes Mellitus in a Medicaid Population.

OBJECTIVE: Our study examines the association between social vulnerability index (SVI) and pharmacotherapy initiation for gestational diabetes mellitus (GDM). METHODS: We studied a retrospective cohort of pregnant patients with GDM, enrolled in Tennessee Medicaid, who gave birth between 2007 and 2019. Enrollment files were linked to birth and death certificates, state hospitalization registries, and pharmacy claims. SVI, measured at the community level and determined by residential census tract, ranged from 0 to 100 (low to high vulnerability). Multivariable logistic regression assessed the association between SVI and the odds of initiating the most common pharmacotherapies for GDM-insulin, glyburide, or metformin-and adjusted for relevant covariates. SVI was modeled with restricted cubic splines to account for nonlinear associations, using the median Tennessee SVI as a reference. Secondary analysis assessed associations with the SVI subthemes. RESULTS: Among 33,291 patients with GDM, 21.7% (7,209) initiated pharmacotherapy during pregnancy. Patients from areas with higher SVI were more likely to be non-Hispanic Black with higher body mass index, whereas those with lower SVI were more likely to be nulliparous. Multivariable modeling demonstrated a complex nonlinear association between SVI and GDM pharmacotherapy initiation, relative to the reference. Higher SVI was associated with elevated odds of GDM pharmacotherapy initiation (e.g., odds ratio 1.11 [95% confidence interval 1.02-1.22] for SVI 80) and low to medium SVI had variable nonsignificant associations with GDM pharmacotherapy initiation, relative to the reference (lower odds of initiation for values 25-50, higher odds of initiation for values < 25). Secondary analysis demonstrated a nonlinear association between subtheme 3 and the odds of GDM pharmacotherapy initiation. CONCLUSION: Social vulnerability is associated with initiation of pharmacotherapy for GDM, highlighting the possible role of social determinants of health in achieving glycemic control.