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.

Economic Burden of Home Antimicrobial Therapy: OPAT Versus Oral Therapy.

BACKGROUND: There is increasing evidence that outpatient parenteral antimicrobial therapy (OPAT) is overused for children and that outcomes with oral therapy are equivalent. Our objective was to compare economic burden between OPAT and oral therapy, accounting for direct and indirect costs and caregiver quality of life (QoL). METHODS: We conducted a prospective cohort study of caregivers for children after hospitalization who were treated with prolonged antimicrobial therapy. We collected data about missed work and school and time spent administering therapy. Caregivers completed the Pediatric Quality of Life Inventory to assess QoL. Clinical information included length of stay, treatment indication, and type of therapy (OPAT versus oral therapy). Direct medical costs were obtained by using a microcosting system and accounted for medication, supplies, and home-nursing visits. The primary cost outcome was the mean daily cost of therapy. Multivariable models were developed to adjust for potential confounders. RESULTS: Two hundred and twelve caregivers completed surveys: 123 (58%) for oral therapy and 89 (42%) for OPAT. Caregivers administering OPAT reported more missed work, missed school for their children, time with daily medication administration (90 vs 6 minutes; P < .01) and lower QoL scores (77.8 vs 68.9) than caregivers administering oral therapy. The mean daily cost was $65 (95% confidence interval: $51-$78) for OPAT and $7 (95% confidence interval: $4-$9) for oral therapy. Relative differences in cost and QoL between groups did not change after model adjustment. CONCLUSIONS: The overall burden of OPAT is substantially higher than that of oral therapy, including higher direct and indirect costs and greater impact on caregiver QoL. These findings strongly support efforts to use oral therapy in place of OPAT when clinically appropriate.

An empirical assessment of the short-term impacts of a reading of Deborah Zoe Laufer's drama Informed Consent on attitudes and intentions to participate in genetic research.

OBJECTIVE: This study assessed the short-term impact of the play "Informed Consent" by Deborah Zoe Laufer (a fictionalized look at the controversy over specimens collected from the Havasupai Tribe for diabetes research in 1989) on perceptions of trust, willingness to donate biospecimens, and attitudes toward harm and privacy among the medical and undergraduate students, faculty, and the public in the Intermountain West. METHODS: Surveys were administered before and after a staged reading of the play by professional actors. Survey items included the short form Trust in Medical Researchers, and single-item questions about group identity, ethics of genetic testing in children, and willingness to donate biospecimens. In addition, respondents were given the option to answer open-ended questions through e-mail. RESULTS: Out of the 481 who attended the play, 421 completed both the pre and post surveys, and 166 participants completed open-ended questions online approximately 1 week after the play. Across all participants, there were significant declines for trust in medical researchers and for the survey item "is it ethical for investigators to test children for adult onset diseases" (p < .001 for both) following the play. There was a significant increase in agreement to improve group identity protections (p < .001) and there were no differences on willingness to donate biospecimens to research (p = .777). Qualitative data provided extensive contextual data supporting these perspectives. DISCUSSION: This is one of the first studies to document short-term impacts of a theatrical performance on both attitudes and behavioral intentions toward research ethics and clinical research participation. Future research should continue to explore the impact of theatrical performances among public and investigators on the ethical issues and complexities in clinical research.

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.

Incidence, Morbidity, and Costs of Human Metapneumovirus Infection in Hospitalized Children.

BACKGROUND: Human metapneumovirus (HMPV) causes acute respiratory tract infections in infants and children. We sought to measure the clinical and economic burden of HMPV infection in hospitalized children. METHODS: We conducted a retrospective cohort study from 2007 to 2013 at Primary Children's Hospital in Salt Lake City, Utah. Children <18 years of age with laboratory-confirmed HMPV infection were included. Demographic, clinical, and financial data were abstracted from the electronic medical record. RESULTS: During the study period, 815 children were hospitalized with laboratory-confirmed HMPV infection: 16% <6 months, 50% 6-23 months, 23% 2-4 years, and 11% 5-17 years of age. A complex chronic condition was identified in 453 (56%) children hospitalized with HMPV infection; this proportion increased with increasing age (P < .001). There was marked variation in annual HMPV hospitalization rates, ranging from 9 of 100 000 person-years in 2012-2013 to 79 of 100 000 in 2009-2010. Hospitalization rates were highest among children <2 years (200 of 100 000 person-years) and lowest among children 5-17 years of age (5 of 100 000). Of hospitalized children, 18% were treated in the intensive care unit and 6% required mechanical ventilation. The median length of stay was 2.8 days (interquartile range [IQR], 1.8-4.6) and did not vary by age. The median total hospital cost per patient was $5513 (IQR, $3850-$9946) with significantly higher costs for patients with chronic medical conditions (P < .001). CONCLUSIONS: Human metapneumovirus infection results in a large number of hospitalizations with substantial morbidity, resource utilization, and costs. The development of a safe and effective vaccine could reduce the clinical and economic burden of HMPV.

A Matrix Mentoring Model That Effectively Supports Clinical and Translational Scientists and Increases Inclusion in Biomedical Research: Lessons From the University of Utah.

Physician-scientists and scientists in all the health professions are vital members of the U.S. biomedical workforce, but their numbers at academic health centers are declining. Mentorship has been identified as a key component in retention of faculty members at academic health centers. Effective mentoring may promote the retention of clinician-scientists in the biomedical workforce. The authors describe a holistic institutional mentoring program to support junior faculty members engaged in clinical and translational science at the University of Utah. The clinical and translational scholars (CATS) program leverages the resources of the institution, including the Center for Clinical and Translational Science, to augment departmental resources to support junior faculty investigators and uses a multilevel mentoring matrix that includes self, senior, scientific, peer, and staff mentorship. Begun in the Department of Pediatrics, the program was expanded in 2013 to include all departments in the school of medicine and the health sciences. During the two-year program, scholars learn management essentials and have leadership training designed to develop principal investigators. Of the 86 program participants since fiscal year 2008, 92% have received extramural awards, 99% remain in academic medicine, and 95% remain at the University of Utah. The CATS program has also been associated with increased inclusion of women and underrepresented minorities in the institutional research enterprise. The CATS program manifests institutional collaboration and coordination of resources, which have benefited faculty members and the institution. The model can be applied to other academic health centers to support and sustain the biomedical workforce.

Outcomes After Skin and Soft Tissue Infection in Infants 90 Days Old or Younger.

BACKGROUND AND OBJECTIVES: Skin and soft tissue infections (SSTIs) are an increasingly common cause of pediatric hospital visits among infants. The optimal evaluation strategy for younger infants with SSTI is unknown because there is little information about outcomes including risks of concomitant bacterial infections and treatment failure. This study was designed to determine rates of concomitant invasive bacterial infection and hospital revisits for treatment failure as well as factors associated with treatment failure in infants presenting with SSTI. METHODS: Retrospective study of patients≤90 days of age who received care from the 22 emergency departments and hospitals in the Intermountain Healthcare system from July 1, 2004 to December 31, 2011, with a primary discharge diagnosis of SSTI. Concomitant bacterial infections were defined as urinary tract infection (UTI; culture-confirmed) or invasive bacterial infection (IBI; culture-confirmed bacteremia and/or meningitis). Treatment failure was defined as any unplanned change in care at hospital revisit within 14 days of discharge. RESULTS: The study included 172 infants; 29 (17%) were febrile, and 91 (53%) had ≥1 sterile site culture performed. One case of bacteremia in a febrile infant was identified giving an overall proportion with UTI/IBI of 0.58% (95% confidence interval 0.01%-3.2%). Sixteen infants (9.3%; 95% confidence interval 5.4%-14.7%) returned for treatment failure. Perianal location (P=.03) and private insurance status (P=.01) were associated with more treatment failures compared with other locations or payer types. No patients returned for missed UTI/IBI. CONCLUSIONS: Concomitant bacterial infections were rare in infants with SSTI, with none identified in afebrile infants. Treatment failure of SSTI leading to hospital revisit was common.

Evaluation and Management of Febrile, Well-appearing Young Infants.

The evaluation and management of well-appearing febrile infants less than 3 months of age has presented a decades-long clinical conundrum for providers. This article reviews the epidemiology of bacterial and viral infections in these infants. It discusses evidence-based diagnostic and treatment strategies, including appropriate use of testing, admission to the hospital, use of antibiotics, and hospital discharge. It also highlights the substantial variation in care for febrile infants and provides strategies to standardize practice.

National trends in the incidence, outcomes and charges of pediatric osteoarticular infections, 1997-2012.

In the United States, the incidence of osteoarticular infections among hospitalized children increased 15% from 2.07 to 2.38 cases per 1000 admissions from 1997 through 2012. The incidence of methicillin-resistant Staphylococcus aureus-coded infections increased from 0.02 to 0.36 cases per 1000 admissions. Methicillin-resistant S. aureus-coded cases had a larger number of therapeutic procedures, longer hospital stays and higher hospital charges.

The CTSA mentored career development program: supporting the careers of child health investigators.

UNLABELLED: Training translational scientists is a priority of the Clinical and Translational Science Award (CTSA) consortium. OBJECTIVES: 1) Describe the landscape of CTSA Mentored Research Career Development Awards (CDA) and 2) evaluate participation and outcomes of child health investigators in these programs. DESIGN: Survey of the CTSA Child Health Oversight Committee (CC-CHOC) and review of nonresponders' CTSA Websites. RESULTS: Thirty-two of 53 CC-CHOC members (60%) responded and all nonresponder Websites were reviewed. Institutions supported 1,166 CDA positions from 2006 to 2011, with 134 awarded to child health investigators (11.5%). Respondents reported a mean of 29.8 KL2 positions (95% CI 17.5-42.2) during their award period, with a mean of 2.8 (95% CI 1.8-3.8) awarded to child health investigators. The proportion of child health awardees varied from 0% to 50% across institutions. We identified 45 subsequent National Institutes of Health (NIH) awards to the 134 child health investigators (34%). CONCLUSIONS: The CTSA program contributes substantially to training the next generation of translational investigators. One-third of child health investigators obtained subsequent NIH awards in the short follow-up period demonstrating success of the CTSA CDA programs. Child health investigators are represented variably across the consortium. Pediatric institutions can partner with the CTSA program to further support training child health investigators.

Costs and infant outcomes after implementation of a care process model for febrile infants.

OBJECTIVE: Febrile infants in the first 90 days may have life-threatening serious bacterial infection (SBI). Well-appearing febrile infants with SBI cannot be distinguished from those without by examination alone. Variation in care resulting in both undertreatment and overtreatment is common. METHODS: We developed and implemented an evidence-based care process model (EB-CPM) for the management of well-appearing febrile infants in the Intermountain Healthcare System. We report an observational study describing changes in (1) care delivery, (2) outcomes of febrile infants, and (3) costs before and after implementation of the EB-CPM in a children's hospital and in regional medical centers. RESULTS: From 2004 through 2009, 8044 infants had 8431 febrile episodes, resulting in medical evaluation. After implementation of the EB-CPM in 2008, infants in all facilities were more likely to receive evidence-based care including appropriate diagnostic testing, determination of risk for SBI, antibiotic selection, decreased antibiotic duration, and shorter hospital stays (P < .001 for all). In addition, more infants had a definitive diagnosis of urinary tract infection or viral illness (P < .001 for both). Infant outcomes improved with more admitted infants positive for SBI (P = .011), and infants at low risk for SBI were more often managed without antibiotics (P < .001). Although hospital admissions were shortened by 27%, there were no cases of missed SBI. Health Care costs were also reduced, with the mean cost per admitted infant decreasing from $7178 in 2007 to $5979 in 2009 (-17%, P < .001). CONCLUSIONS: The EB-CPM increased evidence-based care in all facilities. Infant outcomes improved and costs were reduced, substantially improving value.

Laboratory-Confirmed Rotavirus Disease in Utah Children: Clinical and Economic Impact of Rotavirus Vaccination.

BACKGROUND: Rotavirus is the most common cause of infectious diarrhea in children worldwide. Recent studies have described changes in the burden of all-cause gastroenteritis; however, there are limited data on the clinical and economic impact of rotavirus vaccine on cases of laboratory-confirmed rotavirus disease. METHODS: We performed a retrospective study of laboratory-confirmed rotavirus disease from July 2003 through June 2010 at a children's hospital and a community hospital in Utah. Demographics and hospital costs for children <5 years with rotavirus symptoms and a positive rotavirus enzyme immunoassay test on a stool specimen were abstracted from electronic medical records. We compared the prevaccine period (2003-2007) with the postvaccine period (2008-2010). RESULTS: The overall incidence of rotavirus gastroenteritis declined in the postvaccine period, from 26.6 to 5.2 cases per 10 000 person-years for Salt Lake County residents. The largest decrease in the incidence of rotavirus gastroenteritis was among children <12 months (-87%; 95% confidence interval [CI], 79-93). Older children (12-23 months) also experienced significant decreases (-81%; 95% CI, 72-88), as did those 24-59 months (-61%; 95% CI, 51-71). In 2009, 3 years after rotavirus vaccine introduction, there was a 79% decrease in emergency department visits and a 78% decrease in hospitalizations across both hospitals. The cost of emergency department visits and hospitalizations for rotavirus gastroenteritis decreased by 79% and 72%, respectively, resulting in annual savings of $790 000 at a children's hospital and $140 000 at a community hospital. CONCLUSION: Rotavirus vaccination in infants has dramatically decreased the clinical burden and direct medical costs of rotavirus gastroenteritis in both infants and young children.

The good habit of reading (El Buen Habito de la Lectura): parental reactions to an enhanced Reach Out and Read program in a clinic for the underserved.

This report describes parental reactions to a Reach Out and Read (ROR) program enhanced with a children's library in an urban clinic serving low-income immigrant families.

Clinical and economic outcomes for term infants associated with increasing administration of antibiotics to their mothers.

Implementation of national guidelines for the prevention of group B streptococcal (GBS) infections has led to an increase in intrapartum antibiotic use and reduction in early-onset GBS infections in newborns. Other outcomes, including the clinical diagnosis of sepsis in term infants, treatment with antibiotics, length of stay, and cost have not been described. To examine these outcomes, we performed an analysis of maternal and newborn data collected between 1998 and 2002 of 130 447 in-hospital births of newborns >or=37 weeks gestation and their mothers from a large vertically integrated healthcare organisation in Utah. The main outcome measures included: (i) the number of women delivering at term who received intravenous antibiotics; (ii) the number of newborns treated for 'clinical sepsis', which was defined as receiving antibiotics for >72 h and the number of newborns who received antibiotics for

Metamizole use by Latino immigrants: a common and potentially harmful home remedy.

A 4-year-old boy presented with fever, septic arthritis, and persistent neutropenia. Bone marrow biopsy revealed no evidence of neoplasia. Additional history disclosed that the patient had been given metamizole for pain before onset of his illness. Metamizole, a nonsteroidal antiinflammatory agent, is prohibited in the United States because of the risk of agranulocytosis but is widely used in Mexico and other countries. The increasing number of Latinos in the United States and the extensive cross-border transfer of medicines raise concerns that metamizole use and associated complications may become more frequent. After identification of the index patient, additional inquiry revealed that the patient's mother was hospitalized previously for overwhelming sepsis associated with metamizole use. These cases prompted an investigation of metamizole use in an urban pediatric clinic, which revealed that 35% of Spanish-speaking Latino families had used metamizole; 25% of these families had purchased the medication in the United States. We conclude that metamizole use is common and may be underrecognized in immigrant Latino patients. Physicians in the United States, especially those who practice primary care, hematology/oncology, and infectious diseases, must be aware of the availability and use of metamizole in specific patient populations and its potential for harmful side effects.