National Trends in Voiding Cystourethrograms During Hospitalization for Young Infants With Urinary Tract Infections.

OBJECTIVES: The American Academy of Pediatrics published a guideline in 2011 recommending against the routine use of voiding cystourethrogram (VCUG) in infants aged 2 to 24 months with first febrile urinary tract infection (UTI); however, the rates of VCUG for infants aged <2 months are unknown. The objective of this study was to determine the trend in VCUG performance during index hospitalization among infants aged 0 to 2 months with UTI. METHODS: This retrospective cohort study included infants aged birth to 2 months hospitalized with a UTI from 2008 to 2019 across 38 institutions in the Pediatric Health Information System. Outcome measures included recurrent UTI within 1 year, vesicoureteral reflux diagnosis within 1 year and antiurinary reflux procedure performed within 2 years. Trends over time were compared between preguideline (2008-2011) and postguideline periods (2012-2019) using piecewise mixed-effects logistic regression. RESULTS: The odds of VCUG decreased by 21% per year in the preguideline period (adjusted odds ratio, 0.79; 95% confidence interval, 0.77-0.81; P < .001) versus 20% (adjusted odds ratio, 0.80; 95% confidence interval, 0.77-0.83; P < .001) in the postguideline period. The preguideline and postguideline difference was not statistically significant (P = .60). There was no difference in the postguideline odds of UTI within 1 year (P = .07), whereas the odds of vesicoureteral reflux diagnosis (P < .001) and antiurinary reflux procedure performance (P < .001) decreased. CONCLUSIONS: VCUG performance during hospitalization has declined over the past decade among young infants hospitalized with UTI. Further work is needed to determine the optimal approach to imaging in these young infants.

Diagnostic testing for evaluation of brief resolved unexplained events.

BACKGROUND: Since the publication of the American Academy of Pediatrics (AAP) clinical practice guideline for brief resolved unexplained events (BRUEs), a few small, single-center studies have suggested low yield of diagnostic testing in infants presenting with such an event. We conducted this large retrospective multicenter study to determine the role of diagnostic testing in leading to a confirmatory diagnosis in BRUE patients. METHODS: Secondary analysis from a large multicenter cohort derived from 15 hospitals participating in the BRUE Quality Improvement and Research Collaborative. The study subjects were infants < 1 year of age presenting with a BRUE to the emergency departments (EDs) of these hospitals between October 1, 2015, and September 30, 2018. Potential BRUE cases were identified using a validated algorithm that relies on administrative data. Chart review was conducted to confirm study inclusion/exclusion, AAP risk criteria, final diagnosis, and contribution of test results. Findings were stratified by ED or hospital discharge and AAP risk criteria. For each patient, we identified whether any diagnostic test contributed to the final diagnosis. We distinguished true (contributory) results from false-positive results. RESULTS: Of 2036 patients meeting study criteria, 63.2% were hospitalized, 87.1% qualified as AAP higher risk, and 45.3% received an explanatory diagnosis. Overall, a laboratory test, imaging, or an ancillary test supported the final diagnosis in 3.2% (65/2036, 95% confidence interval [CI] 2.7%-4.4%) of patients. Out of 5163 diagnostic tests overall, 1.1% (33/2897, 95% CI 0.8%-1.5%) laboratory tests and 1.5% (33/2266, 95% CI 1.0%-1.9%) of imaging and ancillary studies contributed to a diagnosis. Although 861 electrocardiograms were performed, no new cardiac diagnoses were identified during the index visit. CONCLUSIONS: Diagnostic testing to explain BRUE including for those with AAP higher risk criteria is low yield and rarely contributes to an explanation. Future research is needed to evaluate the role of testing in more specific, at-risk populations.

Diagnostic testing for and detection of physical abuse in infants with brief resolved unexplained events.

BACKGROUND: A Brief Resolved Unexplained Event (BRUE) can be a sign of occult physical abuse. OBJECTIVES: To identify rates of diagnostic testing able to detect physical abuse (head imaging, skeletal survey, and liver transaminases) at BRUE presentation. The secondary objective was to estimate the rate of physical abuse diagnosed at initial BRUE presentation through 1 year of age. PARTICIPANTS AND SETTING: Infants who presented with a BRUE at one of 15 academic or community hospitals were followed from initial BRUE presentation until 1 year of age for BRUE recurrence or revisits. METHODS: This study was part of the BRUE Research and Quality Improvement Network, a multicenter retrospective cohort examining infants with BRUE. Generalized estimating equations assessed associations with performance of diagnostic testing (adjusted odds ratio (aOR)). RESULTS: Of the 2036 infants presenting with a BRUE, 6.2 % underwent head imaging, 7.0 % skeletal survey, and 12.1 % liver transaminases. Infants were more likely to undergo skeletal survey if there were physical examination findings concerning for trauma (aOR 8.23, 95 % CI [1.92, 35.24], p < 0.005) or concerning social history (aOR 1.89, 95 % CI [1.13, 3.16], p = 0.015). There were 7 (0.3 %) infants diagnosed with physical abuse: one at BRUE presentation, one <3 days after BRUE presentation, and five >30 days after BRUE presentation. CONCLUSION: There were low rates of diagnostic testing and physical abuse identified in infants presenting with BRUE. Further study including standardized testing protocols is warranted to identify physical abuse in infants presenting with a BRUE.

Explanatory Diagnoses Following Hospitalization for a Brief Resolved Unexplained Event.

BACKGROUND AND OBJECTIVES: Most young infants presenting to the emergency department (ED) with a brief resolved unexplained event (BRUE) are hospitalized. We sought to determine the rate of explanatory diagnosis after hospitalization for a BRUE. METHODS: This was a multicenter retrospective cohort study of infants hospitalized with a BRUE after an ED visit between October 1, 2015, and September 30, 2018. We included infants without an explanatory diagnosis at admission. We determined the proportion of patients with an explanatory diagnosis at the time of hospital discharge and whether diagnostic testing, consultation, or observed events occurring during hospitalization were associated with identification of an explanatory diagnosis. RESULTS: Among 980 infants hospitalized after an ED visit for a BRUE without an explanatory diagnosis at admission, 363 (37.0%) had an explanatory diagnosis identified during hospitalization. In 805 (82.1%) infants, diagnostic testing, specialty consultations, and observed events did not contribute to an explanatory diagnosis, and, in 175 (17.9%) infants, they contributed to the explanatory diagnosis (7.0%, 10.0%, and 7.0%, respectively). A total of 15 infants had a serious diagnosis (4.1% of explanatory diagnoses; 1.5% of all infants hospitalized with a BRUE), the most common being seizure and infantile spasms, occurring in 4 patients. CONCLUSIONS: Most infants hospitalized with a BRUE did not receive an explanation during the hospitalization, and a majority of diagnoses were benign or self-limited conditions. More research is needed to identify which infants with a BRUE are most likely to benefit from hospitalization for determining the etiology of the event.

Utility of Inflammatory Markers in Hospitalized Children With Skin Erythema.

BACKGROUND: There is overlap in the clinical presentations of superficial skin infections (eg, cellulitis) and deeper infections (eg, osteomyelitis). Inflammatory markers are frequently obtained in hospitalized patients with cellulitis. However, it is unknown whether inflammatory markers discriminate between superficial and deeper infections. METHODS: We performed a retrospective review of children hospitalized with erythema on the skin and diagnoses of cellulitis, bursitis, myositis, osteomyelitis, and/or tenosynovitis. Patients were grouped into superficial infection (cellulitis and bursitis) and deeper infection (myositis, tenosynovitis, osteomyelitis). We compared C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values between the two groups and constructed receiver operating characteristic curves to determine optimal cutoff values. RESULTS: Among 168 children hospitalized with skin erythema, 122 patients had superficial and 46 patients had deeper infections. Mean CRP and ESR were significantly higher in patients with deeper infections (CRP: 8.3 [±9.6] mg/dL versus 2.8 [±3.5] mg/dL; P < .001; ESR: 48.3 [±28.6] mm/h versus 21.8 [±16.0] mm/h; P < .001). Neither WBC nor fever was significantly different between groups. CRP ≥2 mg/dL and ESR ≥30 mm/h were associated with deeper infections (CRP: odds ratio: 4.77; 95% confidence interval: 2.24-10.15; ESR: odds ratio: 7.93; 95% confidence interval: 3.46-17.67). When CRP and ESR were below these cutoffs, the negative predictive value was 89%. CONCLUSIONS: Among patients presenting with skin erythema, CRP ≥2 mg/dL and ESR ≥30 mm/hr were significantly associated with deeper infection, whereas values below these cutoffs were reassuring against deeper infection. Future study of inflammatory markers in skin and soft tissue infections may help develop tailored testing strategies.

Characterizing Pain Points in Clinical Data Management and Assessing the Impact of Mid-Study Updates.

BACKGROUND: The causes, degree and disruptive nature of mid-study database updates and other pain points were evaluated to understand if and how the clinical data management function is managing rapid growth in data volume and diversity. METHODS: Tufts Center for the Study of Drug Development (Tufts CSDD)-in collaboration with IBM Watson Health-conducted an online global survey between September and October 2020. RESULTS: One hundred ninety four verified responses were analyzed. Planned and unplanned mid-study updates were the top challenges mentioned and their management was time intensive. Respondents reported an average of 4.1 planned and 3.7 unplanned mid-study updates per clinical trial. CONCLUSION: Mid-study database updates are disruptive and present a major opportunity to accelerate cycle times and improve efficiency, particularly as protocol designs become more flexible and the diversity of data, most notably unstructured data, increases.

Evolving Clinical Data Strategies and Tactics in Response to Digital Transformation.

BACKGROUND: Contending with a continuously expanding volume and variety of clinical data poses challenges and opportunities for the industry and clinical data management organizations. METHODS: Tufts CSDD conducted an online survey aimed at further quantifying and understanding the magnitude and impact that expanded data volume, sources and diversity are having on clinical trials. The survey was distributed between October and December 2019. Responses from a total of 149 individuals were included in the final analysis. RESULTS: The survey found that companies use or pilot from one to six different data sources with the majority of respondents using or piloting 3-4 different sources of data in their clinical trials. The results showed that average times to database lock have increased an average 5 days compared to a 2017 study, possibly as a result of managing an even larger number of data sources. Finally, three key mitigation strategies surfaced as techniques respondents used to tackle expanding data volume, sources, and diversity: the creation of a formalized data strategy, investment in new analytics tools and more sophisticated data technology infrastructures, and the development of new data science disciplines. CONCLUSION: Without further investments into infrastructure and developments of additional mitigation techniques in this area, database lock cycle times are likely to continue to increase as more and more data supporting a clinical trial are coming from nontraditional, CRF sources. Further research must be done into organizations who are handling these challenges appropriately.

Encouraging Entrustment: A Qualitative Study of Resident Behaviors That Promote Entrustment.

PURPOSE: To explore resident and attending physician perceptions of resident behaviors and skills that demonstrate trustworthiness and promote entrustment by supervisors. METHOD: Using grounded theory methodology, the authors conducted 3 focus groups with pediatric residents from the Boston Combined Residency Program and 3 focus groups with attending physicians who were either general pediatric hospitalists or other pediatric subspecialists at Boston Children's Hospital and Boston Medical Center in Boston, Massachusetts, from May to December 2018. Data were collected and analyzed iteratively until theoretical saturation was achieved. Three independent reviewers coded each transcript. Codes were grouped into dominant themes to develop a conceptual model. RESULTS: Twelve residents and 18 attending physicians participated in the focus groups. Participants described actions that they felt actively demonstrated residents' trustworthiness within previously described domains of trustworthiness. Four modifiers emerged that affect a resident's progression from trustworthiness to entrustment: (1) self-management, (2) relationships, (3) self-advocacy, and (4) patient-centeredness. Findings were synthesized into a conceptual model depicting how trainees can promote their own entrustment by supervisors. CONCLUSIONS: Trainees must actively demonstrate their trustworthiness to be entrusted. This study proposes that trainees can further gain entrustment through self-management, relationships, self-advocacy, and patient-centeredness. When they understand the actions and behaviors that promote entrustment, trainees may be better able to foster autonomy and progress toward more independent clinical practice. These findings add to existing evidence regarding entrustment and provide a novel, actionable framework for trainees to increase their own entrustment.

Assessing Outsourcing Oversight Practices and Performance.

BACKGROUND: The Tufts Center for the Study of Drug Development conducted a study updating benchmarks on outsourcing model adoption and assessing oversight practices and experience. METHODS: An online survey examining organizational use of clinical development outsourcing was distributed between February and April 2018. Responses from a total of 88 individuals were included in the final analysis. RESULTS: More than half of individuals responding reported using 3 or more models simultaneously, mixing and matching approaches to meet individual project needs. Outsourcing practices among small, medium, and large sponsor companies remain inconsistent and deliver mixed levels of satisfaction and performance. Full-service models are the most commonly used. Biopharmaceutical companies report that the primary purpose of their oversight mechanisms is to minimize risks and regulatory missteps. Oversight mechanisms are generally supported by middle management personnel focusing on more reactive and tactical issues. Executive-level involvement in outsourcing oversight is minimal and highly variable. CONCLUSION: Several opportunities to improve oversight practices were identified in the study, including increasing executive-level involvement and leveraging technologies to monitor performance, enhance communication, and expand collaboration capabilities.

Global Gaps in Training Opportunities for Pediatricians and Pediatric Subspecialists.

OBJECTIVE: A comprehensive, well-trained pediatric workforce is needed to ensure high-quality child health interventions around the globe. Further understanding of pediatric workforce training capacity would assist planning at the global and country level. The purpose of this study was to better understand the availability and process of training programs for pediatricians and pediatric subspecialists worldwide, as well as in-country presence of subspecialists. METHODS: A survey was developed and distributed by e-mail to national pediatric leaders across the globe. The survey asked about the number of pediatric training programs, duration and logistics of training, and whether practicing pediatric subspecialists and subspecialty training programs were available in their country. RESULTS: We received responses from 121 of the 166 countries contacted (73%). Of these, 108 countries reported the presence of one or more general pediatric postgraduate training programs, ranging from 1 to 500 programs per country. The number of training programs did not vary significantly by gross domestic product but did vary by region, with the fewest in Africa (P < .001). Most countries identified national guidelines for training (82% of countries) and accreditation (84% of countries). Availability of pediatric subspecialists varied significantly by income and region, from no subspecialties available in 4 countries to all 26 queried subspecialties available in 17 countries. Neonatology was most common, available in 88% of countries. Subspecialty training programs were less available overall, significantly correlating with country income. CONCLUSION: Education for general pediatrics and pediatric subspecialties is quite limited in many of the countries surveyed, particularly in Africa. The creation of additional educational capacity is a critical issue challenging the adequate provision of pediatrics and pediatric subspecialty services.

Where are the paediatricians? An international survey to understand the global paediatric workforce.

OBJECTIVE: Our primary objective was to examine the global paediatric workforce and to better understand geographic differences in the number of paediatricians globally. Secondary objectives were to describe paediatric workforce expectations, who provides children with preventative care and when children transition out of paediatric care. DESIGN: Survey of identified paediatric leaders in each country. SETTING: Paediatric association leaders worldwide. MAIN OUTCOME MEASURES: Paediatrician numbers, provision of primary care for children, age of transition to adult care. RESULTS: Responses were obtained from 121 countries (73% of countries approached). The number of paediatricians per 100 000 children ranged from a median of 0.5 (IQR 0.3-1.4) in low-income countries to 72 (IQR 4-118) in high-income countries. Africa and South-East Asia reported the lowest paediatrician density (median of 0.8 paediatricians per 100 000 children, IQR 0.4-2.6 and median of 4, IQR 3-9, respectively) and fewest paediatricians entering the workforce. 82% of countries reported transition to adult care by age 18% and 39% by age 15. Most countries (91%) but only 64% of low-income countries reported provision of paediatric preventative care (p<0.001, Cochran-Armitage trend test). Systems of primary care provision varied widely. A majority of countries (63%) anticipated increases in their paediatric workforce in the next decade. CONCLUSIONS: Paediatrician density mirrors known inequities in health provider distribution. Fewer paediatricians are entering the workforce in areas with already low paediatrician density, which may exacerbate disparities in child health outcomes. In some regions, children transition to adult care during adolescence, with implications for healthcare training and delivery. Paediatrician roles are heterogeneous worldwide, and country-specific strategies should be used to address inequity in child health provision.

Baseline Assessment of the Evolving 2017 eClinical Landscape.

The volume and diversity of data collected to support each clinical study has increased dramatically in response to the rising scope and complexity of global drug development programs. The Tufts Center for the Study of Drug Development conducted an online survey of 257 unique global companies-77% drug development sponsors and 23% contract service providers-to assess clinical data management practices and experiences. Study results indicate that companies are using an average of 6 different applications to support each clinical study and that companies are collecting a range of data types including that from case report forms, lab procedures, pharmacokinetics, biomarker, outcomes assessment, mobile health, and social media. Companies report that the primary electronic data capture (EDC) is capturing traditional data types but not many of the newer ones. Respondents report spending an average of 68.3 days to build and release a study database, 8.1 days between the patient visit and when that patient's data are entered into the EDC system, and 36.3 days on average to lock the database following the last patient last visit. Average cycle time durations are longer and more variable than those observed ten years ago. Subgroup differences (eg, by company size and company type) and factors contributing to data management cycle time and experience are discussed.

Assessing Study Start-up Practices, Performance, and Perceptions Among Sponsors and Contract Research Organizations.

BACKGROUND: Site identification, site selection, and study start-up have become the focus of improvement by organizations conducting clinical trials. METHODS: To examine and measure the process from site identification through site activation, Tufts Center for the Study of Drug Development (CSDD) conducted a comprehensive survey among pharmaceutical organizations, biotech companies, and contract research organizations (CROs). Responses from over 400 unique companies were gathered and analyzed. RESULTS: The results indicate that the start-up process is on average 5 to 6 months in total duration, and cycle times across all activities, including site identification, site selection, and study start-up, are faster for repeat sites than for new sites. Comparisons between sponsor and CROs indicate that CROs completed all site-related activities 6 to 11 weeks faster than sponsors. Other areas impacting cycle times were examined, including centralized versus decentralized functions, investment in technology, and organizational strategies that improve cycle time efficiency and performance. CONCLUSION: Tufts CSDD will explore this area in future research to gather additional insights into other factors that may be associated with speed and efficiency.

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement.

Reaching rural Ohio with intellectual disability psychiatry.

Individuals with intellectual disability experience higher rates of mental illness when compared with the general population, and there is a lack of medical and mental health professionals in rural and under-served areas. With the increase in discharge of individuals from institutional settings back to their home communities into the least restrictive environments, there are more patients with complex needs being added to the schedules of physicians in the outpatient delivery care system. Patients with disabilities may not travel well or tolerate changes in routine so may not have access to psychiatry. Utilization of telepsychiatry is well suited to this specialized patient population because it allows a highly traumatized group to meet with a psychiatrist and other mental health professionals from a location of their choice. Ohio's Telepsychiatry Project for Intellectual Disability was initiated in 2012 to serve outlying communities with a lack of infrastructure and resources, to provide specialized mental health services to individuals with co-occurring mental illness and intellectual disability. After five years, over 900 patients with intellectual disability from 64 of Ohio's 88 counties receive specialized mental health treatment through this statewide grant-funded project.