SARS-CoV-2 vaccine testing and trials in the pediatric population: biologic, ethical, research, and implementation challenges.

As the nation implements SARS-CoV-2 vaccination in adults at an unprecedented scale, it is now essential to focus on the prospect of SARS-CoV-2 vaccinations in pediatric populations. To date, no children younger than 12 years have been enrolled in clinical trials. Key challenges and knowledge gaps that must be addressed include (1) rationale for vaccines in children, (2) possible effects of immune maturation during childhood, (3) ethical concerns, (4) unique needs of children with developmental disorders and chronic conditions, (5) health inequities, and (6) vaccine hesitancy. Because COVID-19 is minimally symptomatic in the vast majority of children, a higher acceptable risk threshold is required when evaluating pediatric clinical trials. Profound differences in innate and adaptive immunity during childhood and adolescence are known to affect vaccine responsiveness for a variety of childhood diseases. COVID-19 and the accompanying social disruption, such as the school shutdowns, has been disproportionately damaging to minority and low-income children. In this commentary, we briefly address each of these key issues, specify research gaps, and suggest a broader learning health system approach to accelerate testing and clinical trial development for an ethical and effective strategy to implement a pediatric SARS-CoV-2 vaccine as rapidly and safely as possible. IMPACT: As the US begins an unprecedented implementation of SARS-CoV-2 vaccination, substantial knowledge gaps have yet to be addressed regarding vaccinations in the pediatric population. Maturational changes in the immune system during childhood have influenced the effectiveness of pediatric vaccines for other diseases and conditions, and could affect SARS-CoV-2 vaccine responsiveness in children. Given that COVID-19 disease is far milder in the majority of children than in adults, the risk-benefit of a pediatric SARS-CoV-2 vaccine must be carefully weighed. The needs of children with developmental disabilities and with chronic disease must be addressed. Minority and low-income children have been disproportionately adversely affected by the COVID-19 pandemic; care must be taken to address issues of health equity regarding pediatric SARS-CoV-2 vaccine trials and allocation. Research and strategies to address general vaccine hesitancy in communities must be addressed in the context of pediatric SARS-CoV-2 vaccines.

Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines.

Respiratory syncytial virus (RSV) causes lower respiratory tract illness frequently. No effective antivirals or vaccines for RSV are approved for use in the United States; however, there are at least 50 vaccines and monoclonal antibody products in development, with those targeting older adults and pregnant women (to protect young infants) in phase 2 and 3 clinical trials. Unanswered questions regarding RSV epidemiology need to be identified and addressed prior to RSV vaccine introduction to guide the measurement of impact and future recommendations. The Centers for Disease Control and Prevention (CDC) convened a technical consultation to gather input from external subject matter experts on their individual perspectives regarding evidence gaps in current RSV epidemiology in the United States, potential studies and surveillance platforms needed to fill these gaps, and prioritizing efforts. Participants articulated their individual views, and CDC staff synthesized individuals' input into this report.

Clinical and Epidemiological Evidence of the Red Queen Hypothesis in Pneumococcal Serotype Dynamics.

BACKGROUND: The Red Queen hypothesis is an evolutionary theory that describes the reciprocal coevolution of competing species. We sought to study whether introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) altered pneumococcal serotype dynamics among children with invasive pneumococcal disease (IPD) as predicted by the Red Queen hypothesis. METHODS: This study examined pneumococcal isolates (n = 641) obtained from children <18 years of age hospitalized with IPD from 1997 to 2014 in Utah. A review of the literature also identified several additional studies conducted in the United States and Europe that were used to test the external generalizability of our Utah findings. Simpson's index was used to quantify pneumococcal serotype diversity. RESULTS: In Utah, the introduction of PCV7 and PCV13 was associated with rapid increases in serotype diversity (P < .001). Serotypes rarely present before vaccine introduction emerged as common causes of IPD. Diversity then decreased (P < .001) as competition selected for the fittest serotypes and new evolutionary equilibriums were established. This pattern was also observed more broadly in the United States, the United Kingdom, Norway, and Spain. CONCLUSIONS: This vaccine-driven example of human/bacterial coevolution appears to confirm the Red Queen hypothesis, which reveals a limitation of serotype-specific vaccines and offers insights that may facilitate alternative strategies for the elimination of IPD.

Initial Presentation of Neonatal Herpes Simplex Virus Infection.

OBJECTIVE: To inform the decision to test and empirically treat for herpes simplex virus (HSV) by describing the initial clinical presentation and laboratory findings of infants with a confirmed diagnosis of neonatal HSV. STUDY DESIGN: This is a retrospective case series performed at 2 pediatric tertiary care centers. Infants who developed symptoms prior to 42 days of age with laboratory confirmed HSV from 2002 through 2012 were included. We excluded infants <34 weeks gestation, those who developed illness before discharge from their birth hospital, and those who developed symptoms after 42 days of age. RESULTS: We identified 49 infants with HSV meeting these criteria. Most infants (43/49, 88%) came to medical attention at ≤28 days. Of 49 infants, 22 (45%) had disseminated, 16 (33%) central nervous system, and 10 (20%) skin, eye, mouth HSV disease. Eight infants (16%) had nonspecific presentations without the classic signs of seizure, vesicular rash, or critical illness (intensive care admission). All infants with nonspecific presentation were ≤14 days, had cerebrospinal fluid pleocytosis, or both. CONCLUSIONS: The majority of infants with HSV (84%) presented with seizure, vesicular rash, or critical illness. A subset of patients (16%) lacked classic signs at hospitalization; most manifested signs suggestive of HSV within 24 hours. Further studies are needed to validate the risk factors identified in this study including age <14 days and cerebrospinal fluid pleocytosis at presentation.

Community Surveillance of Respiratory Viruses Among Families in the Utah Better Identification of Germs-Longitudinal Viral Epidemiology (BIG-LoVE) Study.

BACKGROUND: This study: (1) describes the viral etiology of respiratory illness by prospectively collecting weekly symptom diaries and nasal swabs from families for 1 year, (2) analyzed data by reported symptoms, virus, age, and family composition, and (3) evaluated the duration of virus detection. METHODS: Twenty-six households (108 individuals) provided concurrent symptom and nasal swab data for 4166 person-weeks. The FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC) was used to detect 16 respiratory viruses. Viral illnesses were defined as ≥1 consecutive weeks with the same virus detected with symptoms reported in ≥1 week. RESULTS: Participants reported symptoms in 23% and a virus was detected in 26% of person-weeks. Children younger than 5 years reported symptoms more often and were more likely to have a virus detected than older participants (odds ratio [OR] 2.47, 95% confidence interval [CI], 2.08-2.94 and OR 3.96, 95% CI, 3.35-4.70, respectively). Compared with single person households, individuals living with children experienced 3 additional weeks of virus detection. There were 783 viral detection episodes; 440 (56%) associated with symptoms. Coronaviruses, human metapneumovirus, and influenza A detections were usually symptomatic; bocavirus and rhinovirus detections were often asymptomatic. The mean duration of PCR detection was ≤2 weeks for all viruses and detections of ≥3 weeks occurred in 16% of episodes. Younger children had longer durations of PCR detection. CONCLUSIONS: Viral detection is often asymptomatic and occasionally prolonged, especially for bocavirus and rhinovirus. In clinical settings, the interpretation of positive PCR tests, particularly in young children and those who live with them, may be confounded.

Tetanus, diphtheria, acellular pertussis vaccine during pregnancy: pregnancy and infant health outcomes.

OBJECTIVE: To assess pregnancy and birth outcomes in infants born to women who did or did not receive tetanus, diphtheria, acellular pertussis (Tdap) vaccine during pregnancy. STUDY DESIGN: Retrospective cohort. Pregnant women 12-45 years of age who received Tdap at Intermountain Healthcare facilities and their infants were identified and compared with mother-infant pairs without documented Tdap from May 2005 through August 2009. Primary measures included pregnancy outcomes and infant health outcomes at birth through 12 months. RESULTS: From 162,448 pregnancies we identified 138 women (0.08%) with documented Tdap administration during pregnancy (cases); 552 pregnant women without documented Tdap were randomly selected as controls. Of 138 immunized women, 63% received Tdap in the first trimester and 37% after. Tdap was given most commonly as wound prophylaxis. The incidence of spontaneous or elective abortion was no greater in Tdap cases than in controls. There were no significant differences in preterm delivery, gestational age, or birth weight between groups. One or more congenital anomaly was identified in 3.7% (95% CI 1.2%-8.5%) of case infants and 4.4% (95% CI 2.7%-6.5%) of control infants (P = .749). In infants born to women receiving Tdap during pregnancy, 3.6% (0.8%-10.2%) had International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses consistent with complex chronic conditions within 12 months compared with 10.4% (95% CI 7.2%-14.4%) of infants of controls (P = .054). CONCLUSIONS: Documented Tdap administration during pregnancy was uncommon and occurred most often in the first trimester as prophylaxis following trauma. No increase in adverse outcomes was identified in infants born to women receiving Tdap compared with infants of controls.

A Chief Health Security Officer for Every Academic Health Center: Improving Readiness, Response, Recovery, and Resilience.

Academic health centers (AHCs) require expertise to ensure readiness for health security events, such as cyberattacks, natural disasters, and pandemics, as well as the ability to respond to and recover from these events. However, most AHCs lack an individual to coordinate efforts at an enterprise level across academic and operational units during an emergency; elevate the coordination of individual AHCs with local and state public health entities; and through professional organizations, coordinate the work of AHCs across national and international public health entities. Informed by AHCs' responses to the COVID-19 pandemic and a series of focused meetings in 2021 of the Association of Academic Health Centers President's Council on Health Security, the authors propose creating a new C-suite role to meet these critical needs: the chief health security officer (CHSO). The CHSO would be responsible for the AHC's overall health security and would report to the AHC's chief executive officer or president. The authors describe the role of CHSO in relation to the preparation, response, and recovery phases of public health events necessary for health security. They also propose key duties for this position and encourage institutions to offer training and credentials to facilitate the creation and define the portfolios of CHSO positions at AHCs and beyond.

Developing a clinical research infrastructure embedded in an academic medicine center that equitably supports future clinician scientists.

Clinical research in academic medical centers can be difficult to conduct and meet enrollment goals. Students under-represented in medicine (URiM) are also under-represented in academic leadership positions and as physician-scientists but are critical to help solve health disparities. Barriers in pursuing medicine as a career may be high for URiM students, therefore it is important to create pre-medicine opportunities accessible to all students interested in healthcare careers. We describe an undergraduate clinical research platform, the Academic Associate (AcA) program, embedded in the medical system that supports clinical research for academic physician scientists and provides students equitable access to experiences and mentoring opportunities. Students have the opportunity of completing a Pediatric Clinical Research Minor (PCRM) degree. This program satisfies many pre-medicine opportunities for undergraduate students, including those URiM, and allows access to physician mentors and unique educational experiences for graduate school or employment. Since 2009, 820 students participated in the AcA program (17.5% URiM) and 235 students (18% URiM) completed the PCRM. Of the 820 students, 126 (10% URiM) students matriculated to medical school, 128 (11%URiM) to graduate school, and 85 (16.5% URiM) gained employment in biomedical research fields. Students in our program supported 57 publications and were top-enrollers for several multicentered studies. The AcA program is cost-effective and achieves a high level of success enrolling patients into clinical research. Additionally, the AcA program provides equitable access for students URiM to physician mentorship, pre-medical experiences, and an avenue to early immersion in academic medicine.

Second-Line Pharmaceutical Treatments for Patients with Type 2 Diabetes.

Importance: Assessing the relative effectiveness and safety of additional treatments when metformin monotherapy is insufficient remains a limiting factor in improving treatment choices in type 2 diabetes. Objective: To determine whether data from electronic health records across the University of California Health system could be used to assess the comparative effectiveness and safety associated with 4 treatments in diabetes when added to metformin monotherapy. Design, Setting, and Participants: This multicenter, new user, multidimensional propensity score-matched retrospective cohort study with leave-one-medical-center-out (LOMCO) sensitivity analysis used principles of emulating target trial. Participants included patients with diabetes receiving metformin who were then additionally prescribed either a sulfonylurea, dipeptidyl peptidase-4 inhibitor (DPP4I), sodium-glucose cotransporter-2 inhibitor (SGLT2I), or glucagon-like peptide-1 receptor agonist (GLP1RA) for the first time and followed-up over a 5-year monitoring period. Data were analyzed between January 2022 and April 2023. Exposure: Treatment with sulfonylurea, DPP4I, SGLT2I, or GLP1RA added to metformin monotherapy. Main Outcomes and Measures: The main effectiveness outcome was the ability of patients to maintain glycemic control, represented as time to metabolic failure (hemoglobin A1c [HbA1c] ≥7.0%). A secondary effectiveness outcome was assessed by monitoring time to new incidence of any of 28 adverse outcomes, including diabetes-related complications while treated with the assigned drug. Sensitivity analysis included LOMCO. Results: This cohort study included 31 852 patients (16 635 [52.2%] male; mean [SD] age, 61.4 [12.6] years) who were new users of diabetes treatments added on to metformin monotherapy. Compared with sulfonylurea in random-effect meta-analysis, treatment with SGLT2I (summary hazard ratio [sHR], 0.75 [95% CI, 0.69-0.83]; I2 = 37.5%), DPP4I (sHR, 0.79 [95% CI, 0.75-0.84]; I2 = 0%), GLP1RA (sHR, 0.62 [95% CI, 0.57-0.68]; I2 = 23.6%) were effective in glycemic control; findings from LOMCO sensitivity analysis were similar. Treatment with SGLT2I showed no significant difference in effectiveness compared with GLP1RA (sHR, 1.26 [95% CI, 1.12-1.42]; I2 = 47.3%; no LOMCO) or DPP4I (sHR, 0.97 [95% CI, 0.90-1.04]; I2 = 0%). Patients treated with DPP4I and SGLT2I had fewer cardiovascular events compared with those treated with sulfonylurea (DPP4I: sHR, 0.84 [95% CI, 0.74-0.96]; I2 = 0%; SGLT2I: sHR, 0.78 [95% CI, 0.62-0.98]; I2 = 0%). Patients treated with a GLP1RA or SGLT2I were less likely to develop chronic kidney disease (GLP1RA: sHR, 0.75 [95% CI 0.6-0.94]; I2 = 0%; SGLT2I: sHR, 0.77 [95% CI, 0.61-0.97]; I2 = 0%), kidney failure (GLP1RA: sHR, 0.69 [95% CI, 0.56-0.86]; I2 = 9.1%; SGLT2I: sHR, 0.72 [95% CI, 0.59-0.88]; I2 = 0%), or hypertension (GLP1RA: sHR, 0.82 [95% CI, 0.68-0.97]; I2 = 0%; SGLT2I: sHR, 0.73 [95% CI, 0.58-0.92]; I2 = 38.5%) compared with those treated with a sulfonylurea. Patients treated with an SGLT2I, vs a DPP4I, GLP1RA, or sulfonylurea, were less likely to develop indicators of chronic hepatic dysfunction (sHR vs DPP4I, 0.68 [95% CI, 0.49-0.95]; I2 = 0%; sHR vs GLP1RA, 0.66 [95% CI, 0.48-0.91]; I2 = 0%; sHR vs sulfonylurea, 0.60 [95% CI, 0.44-0.81]; I2 = 0%), and those treated with a DPP4I were less likely to develop new incidence of hypoglycemia (sHR, 0.48 [95% CI, 0.36-0.65]; I2 = 22.7%) compared with those treated with a sulfonylurea. Conclusions and Relevance: These findings highlight familiar medication patterns, including those mirroring randomized clinical trials, as well as providing new insights underscoring the value of robust clinical data analytics in swiftly generating evidence to help guide treatment choices in diabetes.

Academic Health Centers and Humanitarian Crises: One Health System's Response to Unaccompanied Children at the Border.

University of California Health (UCH) provided a system-wide, rapid response to the humanitarian crisis of unaccompanied children crossing the southern U.S. border in the midst of the COVID-19 pandemic in 2021. In collaboration with multiple federal, state, and local agencies, UCH mobilized a multidisciplinary team to deliver acute general and specialty pediatric care to unaccompanied children at 2 Californian emergency intake sites (EISs). The response, which did not disrupt normal UCH operations, mobilized the capacities of the system and resulted in a safe and developmentally appropriate environment that supported the physical and mental health of migrant children during this traumatic period. The capacities of UCH's 6 academic health centers ensured access to trauma-informed medical care and culturally sensitive psychological and social support. Child life professionals provided access to exercise, play, and entertainment. Overall, 260 physicians, 42 residents and fellows, 4 nurse practitioners participated as treating clinicians and were supported by hundreds of staff across the 2 EISs. Over 5 months and across both EISs, a total of 4,911 children aged 3 to 17 years were cared for. A total of 782 children had COVID-19, most infected before arrival. Most children (3,931) were reunified with family or sponsors. Continuity of care after reunification or placement in a long-term shelter was enhanced by use of an electronic health record. The effort provided an educational experience for residents and fellows with instruction in immigrant health and trauma-informed care. The effort benefitted from UCH's recent experience of providing a system-wide response to the COVID-19 pandemic. Lessons learned are reported to encourage the alignment and integration of academic health centers' capacities with federal, state, and local plans to better prepare for and respond to the accelerating need to care for those in the wake of disasters and humanitarian crises.

Real-world performance of SARS-Cov-2 serology tests in the United States, 2020.

BACKGROUND: Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation. METHODS: Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters. RESULTS: A total of 15,615 people were observed to have at least one serology test 14-90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79-96%) compared to non-Hispanic (60-89%) patients; in those presenting with at least one COVID-19 related symptom (69-93%) as compared to no such symptoms (63-91%); and in inpatient (70-97%) and emergency department (93-99%) compared to outpatient (63-92%) settings across datasets. PPA was highest in those with diabetes (75-94%) and kidney disease (83-95%); and lowest in those with auto-immune conditions or who are immunocompromised (56-93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59-3.86), patients with diabetes (1.49-1.56), and obesity (1.63-2.23); and lower in those with immunocompromised or autoimmune conditions (0.25-0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets. CONCLUSION: Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests.

Real-world utilization of SARS-CoV-2 serological testing in RNA positive patients across the United States.

BACKGROUND: As diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States. METHODS: Six health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2. RESULTS: Across datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred <14 days from the RNA positive test. The proportion of people with a history of cardiovascular disease, obesity, chronic lung, or kidney disease; or presenting with shortness of breath or pneumonia appeared higher among those serotested compared to those who were not. Even in a population of people with active infection, race/ethnicity data were largely missing (>30%) in some datasets-limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis. CONCLUSION: Our results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources-a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics.

Evolving epidemiologic characteristics of invasive group a streptococcal disease in Utah, 2002-2010.

BACKGROUND: Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity and mortality. Recent national surveillance data report stable rates of invasive GAS disease, although these may not capture geographic variation. METHODS: We performed a population-based, retrospective laboratory surveillance study of invasive GAS disease among Utah residents from 2002-2010. We used Intermountain Healthcare's electronic medical records and data warehouse to identify patients from whom GAS was isolated by culture. We defined clinical syndromes of invasive GAS disease on the basis of International Classification of Diseases, Ninth Revision codes. We abstracted demographic information, comorbidities, and microbiologic and laboratory findings. RESULTS: From 2002-2010, we identified 1514 cases of invasive GAS disease among Utah residents. The estimated mean annual incidence rate was 6.3 cases/100,000 persons, which was higher than the national rate of 3.6 cases/100,000 (P < .01). The incidence of invasive GAS disease in Utah rose from 3.5 cases/100,000 persons in 2002 to 9.8 cases/100,000 persons in 2010 (P = .01). Among children aged <18 years, the incidence of invasive GAS increased from 3.0 cases/100,000 children in 2002 to 14.1 cases/100,000 children in 2010 (P < .01). The increase in the pediatric population was due, in part, to an increase in GAS pneumonia (P = .047). The rate of invasive GAS disease in adults aged 18-64 years increased from 3.4 cases/100 000 persons in 2002 to 7.6 cases/100,000 persons in 2010 (P = .02). Rates among those aged ≥65 years were stable. The incidence of acute rheumatic fever declined from 6.1 to 3.7 cases/100,000 (P = .04). CONCLUSIONS: The epidemiologic characteristics of invasive GAS disease in Utah has changed substantially over the past decade, including a significant increase in the overall incidence of invasive disease-driven primarily by increasing disease in younger persons-that coincided temporally with a decrease in the incidence of acute rheumatic fever.

Executive summary: the management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.

The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.

Normative cerebrospinal fluid profiles in febrile infants.

OBJECTIVE: To describe the cerebrospinal fluid (CSF) profiles of febrile infants aged 1 to 90 days with negative bacterial culture test results and negative results for enteroviruses with polymerase chain reaction. STUDY DESIGN: Statistical analysis of a retrospective cohort. RESULTS: CSF profiles from 823 infants with negative test results for infection were analyzed. For 677 infants with atraumatic lumbar punctures (red blood cell [RBC] count < 1000/mm(3)), the mean and median CSF white blood cell (WBC) counts were 4.3/mm(3) and 3.0/mm(3), respectively, with a range from 0 to 12/mm(3). Mean CSF WBC counts (6.1/mm(3) versus 3.1/mm(3) and 3.0/mm(3)) and protein levels (75.4 mg/dL versus 58.9 mg/dL and 39.2 mg/dL) were higher in the first month compared with months 2 and 3, respectively (P < .001 for all). CSF glucose levels were lower in the first month compared with month 3 (45.3 mg/dL versus 48.0 mg/dL and 57.7 mg/dL; P < .001). Increasing RBC counts were statistically associated with increasing WBC counts (P < .001). However, the contribution of RBC < 10,000/mm(3) was small, and the reference range for WBC in uninfected infants with traumatic lumbar punctures was 0 to 16/mm(3). CONCLUSION: CSF WBC counts in febrile infants without evidence of bacterial or enteroviral infection, even in those with traumatic lumbar puncture, are lower than reported in pediatric references.

Public health communication with frontline clinicians during the first wave of the 2009 influenza pandemic.

CONTEXT: During public health emergencies, office-based frontline clinicians are critical partners in the detection, treatment, and control of disease. Communication between public health authorities and frontline clinicians is critical, yet public health agencies, medical societies, and healthcare delivery organizations have all called for improvements. OBJECTIVES: Describe communication processes between public health and frontline clinicians during the first wave of the 2009 novel influenza A(H1N1) pandemic; assess clinicians' use of and knowledge about public health guidance; and assess clinicians' perceptions and preferences about communication during a public health emergency. DESIGN AND METHODS: During the first wave of the pandemic, we performed a process analysis and surveyed 509 office-based primary care providers in Utah. SETTING AND PARTICIPANTS: Public health and healthcare leaders from major agencies involved in emergency response in Utah and office-based primary care providers located throughout Utah. MAIN OUTCOME MEASURE(S): Communication process and information flow, distribution of e-mails, proportion of clinicians who accessed key Web sites at least weekly, clinicians' knowledge about recent guidance and perception about e-mail load, primary information sources, and qualitative findings from clinician feedback. RESULTS: The process analysis revealed redundant activities and messaging. The 141 survey respondents (28%) received information from a variety of sources: 68% received information from state public health; almost 100% received information from health care organizations. Only one-third visited a state public health or institutional Web site frequently enough (at least weekly) to obtain updated guidance. Clinicians were knowledgeable about guidance that did not change during the first wave; however, correct knowledge was lower after guidance changed. Clinicians felt overwhelmed by e-mail volume, preferred a single institutional e-mail for clinical guidance, and suggested that new information be concise and clearly identified. CONCLUSION: : Communication between public health, health care organizations and clinicians was redundant and overwhelming and can be enhanced considering clinician preferences and institutional communication channels.