Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020.

BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute.

Streptococcal Pharyngitis: Compliance With National Testing Guidelines in a Pediatric Emergency Department.

OBJECTIVES: The Infectious Diseases Society of America (IDSA) guidelines regarding group A streptococcal (GAS) pharyngitis advise against routine testing for patients younger than 3 years, patients without pharyngitis, and patients with symptoms suggesting a viral infection. Group A streptococcal testing may be overused in some clinical settings; thus, we conducted this study to evaluate compliance with the IDSA guidelines in a pediatric emergency department (ED) setting. METHODS: This retrospective cohort study describes patients younger than 18 years presenting to 2 urban pediatric EDs in 2016 who underwent rapid antigen detection testing for GAS pharyngitis. Testing was classified as noncompliant with the IDSA guidelines if the chief complaint was not indicative of GAS infection and/or the patient age was younger than 3 years. Appropriate nonparametric tests compared groups by IDSA testing compliance status. RESULTS: A total of 13,585 patient encounters met inclusion criteria; 5255 (39%) were noncompliant with the IDSA testing guidelines, the majority due to a chief complaint inconsistent with GAS pharyngitis (67%) and secondarily due to the age of younger than 3 years (48%). Among the patients with noncompliant testing, 51% were prescribed an antibiotic, and return encounters were more likely to occur (13% vs 10%, P < 0.001). Return encounters more commonly resulted in respiratory diagnoses in those with noncompliant GAS testing (60% vs 45%, P < 0.001). CONCLUSIONS: Nearly 40% of all pediatric ED encounters with GAS testing were noncompliant with the IDSA guidelines and were associated with greater return encounter rates. Potential negative outcomes from noncompliant GAS testing include misdiagnosis, inappropriate use of antibiotics, allergic reactions, and loss of school days. Informed interventions to reduce unnecessary GAS testing are warranted.

Developing algorithms for identifying major structural birth defects using automated electronic health data.

PURPOSE: Given the 2015 transition to International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic coding, updates to our previously published algorithms for major structural birth defects (BDs) were necessary. Aims of this study were to update, validate, and refine algorithms for identifying selected BDs, and then to use these algorithms to describe BD prevalence in the vaccine safety datalink (VSD) population. METHODS: We converted our ICD-9-CM list of selected BDs to ICD-10-CM using available crosswalks with manual review of codes. We identified, chart reviewed, and adjudicated a sample of infants in the VSD with ≥2 ICD-10-CM diagnoses for one of seven common BDs. Positive predictive values (PPVs) were calculated; for BDs with suboptimal PPV, algorithms were refined. Final automated algorithms were applied to a cohort of live births delivered 10/1/2015-9/30/2017 at eight VSD sites to estimate BD prevalence. This research was approved by the HealthPartners Institutional Review Board, by all participating VSD sites, and by the CDC, with a waiver of informed consent. RESULTS: Of 573 infants with ≥2 diagnoses for a targeted BD, on adjudication, we classified 399 (69.6%) as probable cases, 31 (5.4%) as possible cases and 143 (25.0%) as not having the targeted BD. PPVs for the final BD algorithms ranged from 0.76 (hypospadias) to 1.0 (gastroschisis). Among 212 857 births over 2 years following transition to ICD-10-CM coding, prevalence for the full list of selected defects in the VSD was 1.8%. CONCLUSIONS: Algorithms can identify infants with selected BDs using automated healthcare data with reasonable accuracy. Our updated algorithms can be used in observational studies of maternal vaccine safety and may be adapted for use in other surveillance systems.

Organ Donation Authorization After Brain Death Among Patients Admitted to PICUs in the United States, 2009-2018.

OBJECTIVES: To identify trends in and factors associated with pediatric organ donation authorization after brain death. DESIGN: Retrospective cohort study of data from Virtual Pediatric Systems, LLC (Los Angeles, CA). SETTING: Data from 123 PICUs reporting to Virtual Pediatric Systems from 2009 to 2018. PATIENTS: Patients less than 19 years old eligible for organ donation after brain death. MEASUREMENTS AND MAIN RESULTS: Of 2,777 eligible patients, 1,935 (70%) were authorized for organ donation; the authorization rate remained unchanged over time (ptrend = 0.22). In a multivariable logistic regression model, hospitalizations lasting greater than 7 days had lower odds of authorization (adjusted odds ratio, 0.5; p < 0.001 vs ≤ 1 d) and White patients had higher odds than other race/ethnicity groups. Authorization was higher for trauma-related encounters (adjusted odds ratio, 1.5; p < 0.001) and when donation was discussed with an organ procurement organization coordinator (adjusted odds ratio, 1.7; p < 0.001). Of 123 hospitals, 35 (28%) met or exceeded a 75% organ donation authorization target threshold; these hospitals more often had an organ procurement organization coordinator discussing organ donation (85% vs 72% of encounters; p < 0.001), but no difference was observed by PICU bed size. CONCLUSIONS: Organ donation authorization after brain death among PICU patients was associated with length of stay, race/ethnicity, and trauma-related encounter, and authorization rates were higher when an organ procurement organization coordinator was involved in the donation discussion. This study identified factors that could inform initiatives to improve the authorization process and increase pediatric organ donation rates.

Emergency Department Visits for Pediatric Firearm Injuries by Trauma Center Type.

OBJECTIVES: This study aimed to characterize pediatric visits to emergency departments (EDs) for firearm injuries and examine differences by trauma center type. METHODS: Analyses included all patients younger than 19 years from the National Trauma Data Bank, years 2009 to 2014. Trauma centers were categorized as adult, mixed adult and pediatric, or pediatric based on certification level. Baseline characteristics were compared between subgroups using χ2 tests. Multivariable logistic regression was used to examine risk of death. RESULTS: Of 466,403 pediatric ED visits, 21,416 (4.6%) resulted from a firearm injury. Most firearm injuries were treated at an adult (64.9%) or mixed trauma center (29.1%) and involved patients that were male (87.1%), in the 15- to 18-year age group (83.2%), and black or African American (61.3%). Most visits were for injuries resulting from assault (78.1%), followed by unintentional (12.6%) and self-inflicted (4.7%) injuries, undetermined intent (3.7%), and legal intervention (0.8%). Patients visiting EDs for firearm injuries had more than 7 times the odds of dying compared with patients with other injuries (odds ratio, 7.30; 95% confidence interval, 6.82-7.72), and firearm injuries were responsible for more than a quarter (26.1%) of the total pediatric deaths in the National Trauma Data Bank (n = 2866). Assault-related injuries resulted in the most deaths (n = 2010; 70.1%), but the case fatality rate was highest for self-inflicted (n = 453; 44.6%). CONCLUSION: We identified more than 20,000 firearm-related ED visits by pediatric patients from 2009 to 2014, averaging nearly 10 visits per day. Findings from this study can inform strategic planning in hospitals focused on preventing firearm injuries in children and adolescents.

Epidemiology of Bloodstream Infections in Hospitalized Children in the United States, 2009-2016.

BACKGROUND: Bloodstream infections (BSIs) cause significant morbidity and mortality in children. Recent pediatric epidemiological data may inform prevention strategies and empiric antimicrobial therapy selection. METHODS: We conducted a retrospective cohort study from 2009 through 2016 utilizing demographic and microbiologic data on inpatients aged <19 years using the Premier Healthcare Database. BSIs were positive blood cultures without known contaminants. Hospitalization rate was the number of BSI-positive encounters per 1000 admissions. Community-acquired infections (CAIs) were cultures positive ≤2 days of admission among nonneonates. BSI patients were compared to documented positive BSI patients (non-BSI); differences were analyzed using χ2 test, t test, and Cochran-Armitage test for time trends. RESULTS: Among 1 809 751 encounters from 162 US hospitals, 5340 (0.30%) were BSI positive; CAIs were most common (50%). BSI patients were more often aged 1-5 years and had complex chronic conditions or central lines compared to non-BSI patients. The BSI hospitalization rate declined nonsignificantly over time (3.13 in 2009 to 2.98 in 2016, P = .08). Among pathogens, Escherichia coli (0.80 to 1.26), methicillin-sensitive Staphylococcus aureus (0.83 to 1.98), and group A Streptococcus (0.16 to 0.37) significantly increased for nonneonates, while Streptococcus pneumoniae (1.07 to 0.26) and Enterococcus spp. (0.60 to 0.17) declined. Regional differences were greatest for E. coli and highest in the New England and South Atlantic regions. CONCLUSIONS: Trends in pediatric BSI hospitalization rates varied by pathogen and regionally. Overall the BSI hospitalization rate did not significantly decline, indicating a continued need to improve pediatric BSI assessment and prevention.

Risk-Set Matching to Assess the Impact of Hospital-Acquired Bloodstream Infections.

Hospital-acquired bloodstream infections have a definite impact on patient encounters and cause increased length of stay, costs, and mortality. However, methods for estimating these effects are potentially biased, especially if the time of infection is not incorporated into the estimation strategy. We focused on matching patient encounters in which a hospital-acquired infection occurred to comparable encounters in which an infection did not occur. This matching strategy is susceptible to a selection bias because inpatients that stay longer in the hospital are more likely to acquire an infection and thus also are more likely to have longer and more costly stays. Instead, we have proposed risk-set matching, which matches infected encounters to similar encounters still at risk for infection at the corresponding time of infection. Matching on the one-dimensional propensity score can create comparable pairs for a large number of characteristics; an analogous propensity score is described for risk-set matching. We have presented dramatically different estimates using these 2 approaches with data from a pediatric cohort from the Premier Healthcare Database, United States, 2009-2016. The results suggest that estimates that did not incorporate time of infection exaggerated the impact of hospital-acquired infections with regard to attributed length of stay and costs.

ZAP-VAP: A Quality Improvement Initiative to Decrease Ventilator-Associated Pneumonia in the Neonatal Intensive Care Unit, 2012-2016.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the second most frequent hospital-acquired infection in neonatal intensive care units (NICUs) and significantly affects neonatal morbidity and mortality. The population most at risk for VAP are extremely preterm infants. PURPOSE: The objectives of this quality improvement project were to create and evaluate the effectiveness of a VAP prevention bundle ("ZAP-VAP") in reducing VAP. METHODS: The development of the ZAP-VAP bundle and creation of audit tools were documented. A targeted gestational age less than 29 weeks was selected for this study. Electronic medical record review was used to determine the preintervention baseline for patient outcomes. Patient medical record data were analyzed retrospectively to measure patient outcomes preimplementation. VAP rates (number of VAP cases per 1000 ventilator days) were calculated pre- and postintervention. After implementation, data were analyzed prospectively to measure patient outcomes between neonates who developed VAP and those who did not. RESULTS: The VAP rate significantly decreased from 8.5 (2010-2011) to 2.5 (P= .0004) postintervention (2016). Median mechanical ventilation days decreased among VAP cases (47 vs 33 days) and slightly increased among non-VAP cases (19 vs 24 days) during the intervention period. Median length of stay decreased for VAP cases (136 vs 100 days) but remained unchanged for non-VAP cases (85 vs 84 days). IMPLICATIONS FOR PRACTICE: The intervention was implemented from 2012 to 2016. The protocol was readily accepted by our neonatal intensive care unit (NICU) team through education and practice changes. ZAP-VAP is an effective and straightforward protocol that improved VAP outcomes in our level IIIB NICU. An interdisciplinary team successfully implemented this intervention for mechanically ventilated infants of all gestational ages in our unit and has been a model for these practice changes in other units and other hospitals. IMPLICATIONS FOR RESEARCH: Future studies should focus on how to create sustainable interventions to decrease VAP in NICUs and to expand the approaches to other units in our hospital and other hospitals in our city among patients at risk for VAP.

Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents.

Background: Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic. Methods: The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories. Results: Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0. Conclusion: Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.

Long-term Follow-up of Patients With Lyme Disease: Longitudinal Analysis of Clinical and Quality-of-life Measures.

BACKGROUND: Lyme disease is the most common vector-borne disease in the United States. Some patients report persistent or intermittent subjective symptoms of mild to moderate intensity after antibiotic treatment for Lyme disease. We sought to evaluate trends in clinical and quality-of-life (QOL) measures in a cohort of patients with Lyme disease enrolled in a natural history study at the National Institutes of Health from 2001-2014. METHODS: QOL was measured using the self-administered 36-item Short Form Health Survey (SF-36) during study follow-up. Primary outcomes included mean physical (PCS) and mental (MCS) health QOL composite scores and reporting long-term (≥2 years) symptoms, adjusted for Lyme disease stage and severity at diagnosis. RESULTS: Overall, 101 patients with an average follow-up time of 3.9 years (range, 0.5-11.3 years) were included. At first visit, overall mean QOL scores were below the US population mean for both PCS (45.6 ± 10.4) and MCS (47.3 ± 11.5) but increased to just above the national average after 3 years of follow-up for both PCS (50.7 ± 9.6) and MCS (50.1 ± 10.0). Baseline QOL scores were lowest in those with late disease (P < 0.01) but also increased by the end of follow-up to national averages. In multivariate analysis, the only factors significantly associated with long-term symptoms or lower QOL scores were other comorbidities unrelated to Lyme disease. CONCLUSIONS: Comorbid conditions can play a role in the reporting of long-term symptoms and overall QOL of Lyme disease patients and should be considered in the evaluation of these patients. CLINICAL TRIALS REGISTRATION: NCT00028080.

Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

BACKGROUND: The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. OBJECTIVES: To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. SEARCH METHODS: We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV. DATA COLLECTION AND ANALYSIS: Two review authors assessed each reference for inclusion using exclusion criteria that we had established a priori. Two review authors independently extracted data from each included trial using a standardized data extraction form. We analysed data on an intention-to-treat basis. We performed subgroup analyses for concurrent treatment for tuberculosis and dosage of NVP. We followed standard Cochrane methodological procedures. MAIN RESULTS: Twelve RCTs, which included 3278 participants, met our inclusion criteria. None of these trials included children. The length of follow-up time, study settings, and NRTI combination drugs varied greatly. In five included trials, participants were receiving concurrent treatment for tuberculosis.There was little or no difference between EFV and NVP in virological success (RR 1.04, 95% CI 0.99 to 1.09; 10 trials, 2438 participants; high quality evidence), probably little or no difference in mortality (RR 0.84, 95% CI 0.59 to 1.19; 8 trials, 2317 participants; moderate quality evidence) and progression to AIDS (RR 1.23, 95% CI 0.72 to 2.11; 5 trials, 2005 participants; moderate quality evidence). We are uncertain whether there is a difference in all severe adverse events (RR 0.91, 95% CI 0.71 to 1.18; 8 trials, 2329 participants; very low quality evidence). There is probably little or no difference in discontinuation rate (RR 0.93, 95% CI 0.69 to 1.25; 9 trials, 2384 participants; moderate quality evidence) and change in CD4 count (MD -3.03; 95% CI -17.41 to 11.35; 9 trials, 1829 participants; moderate quality evidence). There may be little or no difference in treatment failure (RR 0.97, 95% CI 0.76 to 1.24; 5 trials, 737 participants; low quality evidence). Development of drug resistance is probably slightly less in the EFV arms (RR 0.76, 95% CI 0.60 to 0.95; 4 trials, 988 participants; moderate quality evidence). No studies were found that looked at sexual transmission of HIV.When we examined the adverse events individually, EFV probably is associated with more people with impaired mental function (7 per 1000) compared to NVP (2 per 1000; RR 4.46, 95% CI 1.65 to 12.03; 6 trials, 2049 participants; moderate quality evidence) but fewer people with elevated transaminases (RR 0.52, 95% CI 0.35 to 0.78; 3 trials, 1299 participants; high quality evidence), fewer people with neutropenia (RR 0.48, 95% CI 0.28 to 0.82; 3 trials, 1799 participants; high quality evidence), and probably fewer people withrash (229 per 100 with NVP versus 133 per 1000 with EFV; RR 0.58, 95% CI 0.34 to 1.00; 7 trials, 2277 participants; moderate quality evidence). We found that there may be little or no difference in gastrointestinal adverse events (RR 0.76, 95% CI 0.48 to 1.21; 6 trials, 2049 participants; low quality evidence), pyrexia (RR 0.65, 95% CI 0.15 to 2.73; 3 trials, 1799 participants; low quality evidence), raised alkaline phosphatase (RR 0.65, 95% CI 0.17 to 2.50; 1 trial, 1007 participants; low quality evidence), raised amylase (RR 1.40, 95% CI 0.72 to 2.73; 2 trials, 1071 participants; low quality evidence) and raised triglycerides (RR 1.10, 95% CI 0.39 to 3.13; 2 trials, 1071 participants; low quality evidence). There was probably little or no difference in serum glutamic oxaloacetic transaminase (SGOT; MD 3.3, 95% CI -2.06 to 8.66; 1 trial, 135 participants; moderate quality evidence), serum glutamic- pyruvic transaminase (SGPT; MD 5.7, 95% CI -4.23 to 15.63; 1 trial, 135 participants; moderate quality evidence) and raised cholesterol (RR 6.03, 95% CI 0.75 to 48.78; 1 trial, 64 participants; moderate quality evidence).Our subgroup analyses revealed that NVP slightly increases mortality when given once daily (RR 0.34, 95% CI 0.13 to 0.90; 3 trials, 678 participants; high quality evidence). There were little or no differences in the primary outcomes for patients who were concurrently receiving treatment for tuberculosis. AUTHORS' CONCLUSIONS: Both drugs have similar benefits in initial treatment of HIV infection when combined with two NRTIs. The adverse events encountered affect different systems, with EFV more likely to cause central nervous system adverse events and NVP more likely to raise transaminases, cause neutropenia and rash.

Predicting the impact of COVID-19 non-pharmaceutical intervention on short- and medium-term dynamics of enterovirus D68 in the US.

Recent outbreaks of enterovirus D68 (EV-D68) infections, and their causal linkage with acute flaccid myelitis (AFM), continue to pose a serious public health concern. During 2020 and 2021, the dynamics of EV-D68 and other pathogens have been significantly perturbed by non-pharmaceutical interventions against COVID-19; this perturbation presents a powerful natural experiment for exploring the dynamics of these endemic infections. In this study, we analyzed publicly available data on EV-D68 infections, originally collected through the New Vaccine Surveillance Network, to predict their short- and long-term dynamics following the COVID-19 interventions. Although long-term predictions are sensitive to our assumptions about underlying dynamics and changes in contact rates during the NPI periods, the likelihood of a large outbreak in 2023 appears to be low. Comprehensive surveillance data are needed to accurately characterize future dynamics of EV-D68. The limited incidence of AFM cases in 2022, despite large EV-D68 outbreaks, poses further questions for the timing of the next AFM outbreaks.

Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study.

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6-18 months. Overall, 174 children were enrolled in Cohort 1 of the study and 120 (69 %) of children completed the study, with follow-up blood samples obtained from 101 (58 %) of participants. Families were primarily motivated to participate by a desire to help other children, advance science, and better prepare for the next pandemic. Adding research blood draws to clinically indicated blood draws improved enrollment, and multiple study touch points facilitated retention. These findings can be applied to improve recruitment and retention in future pandemic preparedness efforts and longitudinal pediatric cohort studies.

Gonorrhoea or chlamydia in a U.S. military HIV-positive cohort.

OBJECTIVES: To investigate the epidemiology and risk factors of gonorrhoea (GC) or chlamydia (CT) coinfection in an HIV-positive US military cohort, focusing on the time after participants' knowledge of HIV diagnosis. METHODS: The authors analysed data from 4461 participants enrolled in the U.S. Military Natural History Study cohort for GC or CT infection ≥6 months after their HIV-positive test. RESULTS: During a mean follow-up of 7.08 years, 482 (11%) participants acquired a GC or CT infection. Of these, 283 (6%) acquired a GC infection, 278 (6%) acquired a CT infection and 123 (3%) had multiple GC or CT infections during follow-up. Risk of GC or CT infection was significantly greater in those younger, male, African-American and with a history of GC or CT infection. CONCLUSIONS: Frequent GC and CT diagnoses observed among members of this HIV-positive cohort indicate substantial ongoing risk behaviours that raise concerns for HIV transmission and underscore the need for continued screening to help identify and treat these sexually transmitted infections in this population.

Integration of HIV/AIDS services with maternal, neonatal and child health, nutrition, and family planning services.

BACKGROUND: The integration of HIV/AIDS and maternal, neonatal, child health and nutrition services (MNCHN), including family planning (FP) is recognized as a key strategy to reduce maternal and child mortality and control the HIV/AIDS epidemic. However, limited evidence exists on the effectiveness of service integration. OBJECTIVES: To evaluate the impact of integrating MNCHN-FP and HIV/AIDS services on health, behavioral, and economic outcomes and to identify research gaps. SEARCH METHODS: Using the Cochrane Collaboration's validated search strategies for identifying reports of HIV interventions, along with appropriate keywords and MeSH terms, we searched a range of electronic databases, including the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE (via PubMed), and Web of Science / Web of Social Science. The date range was from 01 January 1990 to 15 October 2010. There were no limits to language. SELECTION CRITERIA: Included studies were published in peer-reviewed journals, and provided intervention evaluation data (pre-post or multi-arm study design).The interventions described were organizational strategies or change, process modifications or introductions of technologies aimed at integrating MNCHN-FP and HIV/AIDS service delivery. DATA COLLECTION AND ANALYSIS: We identified 10,619 citations from the electronic database searches and 101 citations from hand searching, cross-reference searching and interpersonal communication. After initial screenings for relevance by pairs of authors working independently, a total of 121 full-text articles were obtained for closer examination. MAIN RESULTS: Twenty peer-reviewed articles representing 19 interventions met inclusion criteria. There were no randomized controlled trials. One study utilized a stepped wedge design, while the rest were non-randomized trials, cohort studies, time series studies, cross-sectional studies, serial cross-sectional studies, and before-after studies. It was not possible to perform meta-analysis. Risk of bias was generally high. We found high between-study heterogeneity in terms of intervention types, study objectives, settings and designs, and reported outcomes. Most studies integrated FP with HIV testing (n=7) or HIV care and treatment (n=4). Overall, HIV and MNCHN-FP service integration was found to be feasible across a variety of integration models, settings and target populations. Nearly all studies reported positive post-integration effects on key outcomes including contraceptive use, antiretroviral therapy initiation in pregnancy, HIV testing, and quality of services. AUTHORS' CONCLUSIONS: This systematic review's findings show that integrated HIV/AIDS and MNCHN-FP services are feasible to implement and show promise towards improving a variety of health and behavioral outcomes. However, significant evidence gaps remain. Rigorous research comparing outcomes of integrated with non-integrated services, including cost, cost-effectiveness, and health outcomes such as HIV and STI incidence, morbidity and mortality are greatly needed to inform programs and policy.

Inpatient and Outpatient Differences in Pediatric Patients with Laboratory-confirmed COVID-19.

Among 30,286 pediatric inpatient and outpatient encounters with laboratory-confirmed COVID-19 seen at one of 40 US healthcare organizations, 1586 (5.2%) were inpatient. Encounter types varied by age and sex; the proportion of Black/African American inpatients was significantly higher than outpatients, and Hispanic/Latinx children made up nearly one-fourth of patients.

Sexual and reproductive health services for people living with HIV: a systematic review.

People living with HIV often have unmet needs for sexual and reproductive health (SRH) services. We present results of a systematic review of studies offering SRH services targeted to people living with HIV. Studies were selected from a broader SRH and HIV linkages review. Inclusion criteria included: (1) peer-reviewed journal articles with a pre-post or multiple-arm study design; (2) reported post-intervention evaluation data; and (3) published 1 January 1990 through 31 December 2007. Nine studies were identified with an average rigour score of 5.1 out of 9. Services included family planning (one study), sexually transmitted infection (STI) services (two studies), combined family planning and STI services (three studies) and multiple services (three studies). The review identified mostly positive effects on the outcomes measured, including condom and contraceptive use and quality of services. Yet gaps remain in the research to establish the best approaches for addressing needs and choices of people living with HIV. There is a need for high-quality intervention studies to determine the most successful and cost-effective strategies for providing SRH services to people living with HIV.

Trends in Pediatric Viral Symptoms, Influenza Testing, and SARS-CoV-2 Testing From a Statewide Electronic Health Record Consortium, January 2017 to July 2021.

OBJECTIVE: The heterogeneous implementation and uptake of nonpharmaceutical interventions (NPIs) during the coronavirus disease 2019 (COVID-19) pandemic amplified the need for locally responsive disease surveillance mechanisms. Using data from a newly developed statewide electronic health record (EHR) consortium in Minnesota, we sought to characterize trends in pediatric viral symptoms, influenza testing, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. METHODS: We conducted a serial cross-sectional analysis of EHR data from 1/1/2017 to 7/30/2021 across 8 large health systems in Minnesota. We included patients ≤18 years of age with any SARS-CoV-2 test, influenza test, or documented diagnostic code which met our viral symptom definition. We plotted week-by-week trends in viral symptoms, SARS-CoV-2 and influenza testing, and test positivity, stratified between children (0-11 years) and adolescents (12-18 years). RESULTS: We identified 1,079,924 patients ≤18 years of age with viral symptoms or testing; 880,669 (81.5%) were children ≤11 years. Influenza testing and influenza test positivity remained well below historical averages from March 2020 through mid-May 2021. Peaks in viral symptoms during this time were concomitant with peaks in SARS-CoV-2 testing and test positivity, whereas influenza testing and test positivity remained stagnant. Influenza test positivity rates increased substantively among children from May through July 2021. CONCLUSIONS: Viral illness and influenza testing among pediatric patients were below historical averages throughout the COVID-19 pandemic. Ongoing increases in influenza test positivity may merit clinical and public health awareness and intervention. Future NPI policies can be better targeted with insights from collaborative EHR-based surveillance, which enhances real-time, locally sensitive measurement of disease outbreaks.

Factors Associated With COVID-19 Disease Severity in US Children and Adolescents.

BACKGROUND: Little is known about the clinical factors associated with COVID-19 disease severity in children and adolescents. METHODS: We conducted a retrospective cohort study across 45 US children's hospitals between April 2020 to September 2020 of pediatric patients discharged with a primary diagnosis of COVID-19. We assessed factors associated with hospitalization and factors associated with clinical severity (eg, admission to inpatient floor, admission to intensive care unit [ICU], admission to ICU with mechanical ventilation, shock, death) among those hospitalized. RESULTS: Among 19,976 COVID-19 encounters, 15,913 (79.7%) patients were discharged from the emergency department (ED) and 4063 (20.3%) were hospitalized. The clinical severity distribution among those hospitalized was moderate (3222, 79.3%), severe (431, 11.3%), and very severe (380, 9.4%). Factors associated with hospitalization vs discharge from the ED included private payor insurance (adjusted odds ratio [aOR],1.16; 95% CI, 1.1-1.3), obesity/type 2 diabetes mellitus (type 2 DM) (aOR, 10.4; 95% CI, 8.9-13.3), asthma (aOR, 1.4; 95% CI, 1.3-1.6), cardiovascular disease, (aOR, 5.0; 95% CI, 4.3- 5.8), immunocompromised condition (aOR, 5.9; 95% CI, 5.0-6.7), pulmonary disease (aOR, 5.3; 95% CI, 3.4-8.2), and neurologic disease (aOR, 3.2; 95% CI, 2.7-5.8). Among children and adolescents hospitalized with COVID-19, greater disease severity was associated with Black or other non-White race; age greater than 4 years; and obesity/type 2 DM, cardiovascular, neuromuscular, and pulmonary conditions. CONCLUSIONS: Among children and adolescents presenting to US children's hospital EDs with COVID-19, 20% were hospitalized; of these, 21% received care in the ICU. Older children and adolescents had a lower risk for hospitalization but more severe illness when hospitalized. There were differences in disease severity by race and ethnicity and the presence of selected comorbidities. These factors should be taken into consideration when prioritizing mitigation and vaccination strategies.