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Objective: To improve appropriate antibiotic prescribing for children in Tennessee., Design: We performed a before-and-after intervention study with 3 comparison periods: period 1 (P1, baseline) May 2018-September 2019; period 2 (P2, intervention before the COVID-19 pandemic) November 11, 2019-March 20, 2020; and period 3 (P3, intervention during the coronavirus disease 2019 [COVID-19] pandemic) March 21, 2020-November 10, 2020. We additionally surveyed participating providers to assess acceptance of the intervention., Setting: Community general pediatrics practices., Participants: In total, 81 general pediatricians, family medicine physicians, and nurse practitioners in 5 general pediatrics practices participated in this study., Interventions: Each practice identified a practice and operations champion for the project. Practices chose 2-4 implementation strategies previously shown to be effective at reducing outpatient antibiotic use to implement in their practice throughout the study intervention period. Study personnel also held quarterly meetings with all providers to review deidentified peer comparison feedback both across practices enrolled in the study and at the provider level within each practice., Results: We detected improvements in guideline-concordant antibiotic use in the pre-COVID-19 intervention period, and they were sustained in the study period during the pandemic (P3): otitis media (P1 72.14% vs P2 81.42% vs P3 86.11%), group A streptococcal pharyngitis (P1 66.13% vs P2 81.56% vs P3 80.44%), pneumonia (P1 70.6% vs P2 76.2% vs P3 100%), sinusitis (P1 76.2% vs P2 83.78% vs P3 82.86%), skin and soft-tissue infections (P1 97.18% vs P2 100% vs P3 100%)., Conclusions: Bundled implementation strategies led to significant increases in guideline-concordant antibiotic prescribing for all diagnoses. Survey results demonstrate that the bundled implementation strategies were well-accepted by providers.

We surveyed pediatric antimicrobial stewardship program (ASP) site leaders within the Sharing Antimicrobial Reports for Pediatric Stewardship collaborative regarding discharge stewardship practices. Among 67 sites, 13 (19%) reported ASP review of discharge antimicrobial prescriptions. These findings highlight discharge stewardship as a potential opportunity for improvement during the hospital-to-home transition.

Antibiotic use is common in the neonatal intensive care unit. The density and heterogeneity of antibiotic prescribing suggests inappropriate and overuse of these agents. Potential antibiotic stewardship targets include sepsis, necrotizing enterocolitis, and perioperative prophylaxis. Diagnostic stewardship principles, including appropriately obtained cultures, may be leveraged to decrease unnecessary antibiotic prescribing. Strategies including guideline development, prospective audit and feedback, and formulary restriction have been successfully deployed in the neonatal intensive care unit to improve the quality of antibiotic prescribing. Implementation of antibiotic stewardship in the neonatal intensive care unit requires multidisciplinary collaboration between neonatologists, surgeons, infectious diseases specialists, pharmacists, and nurses., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The utility of procalcitonin testing in the pediatric intensive care unit (PICU) is not known. We sought to determine the impact of a procalcitonin-guided antibiotic treatment algorithm implemented with antibiotic stewardship (AS) guidance vs. usual care on antibiotic use in critically ill children., Methods: Single center, pragmatic, randomized prospective clinical trial of critically ill children admitted to an ICU setting and started on intravenous antibiotics from February 15, 2018, to April 11, 2019. Patients were assigned on a monthly basis to either the procalcitonin or usual care arm. The procalcitonin arm had procalcitonin testing on hospital days 0, 1, 2, and 4 and stewardship assistance with algorithm result interpretation. Both arms had routine AS audit and feedback. The primary outcome was median antibiotic days of therapy per patient in the first 14-days after enrollment., Results: Among 270 patients, 137 were in the procalcitonin arm and 133 in the usual care arm. Antibiotic days of therapy (DOT) were not significantly different between the procalcitonin arm (6.6, IQR: 3.1-10.9) and the usual care arm (7.6, IQR: 3-11.8; P = 0.37). More AS recommendations were made in the procalcitonin vs. control arm (54 vs. 37; P = 0.03). Adherence with algorithm-based antibiotic recommendations was high in the procalcitonin arm (70%)., Conclusions: We found no difference in antibiotic DOT between study arms. This trial was underpowered but demonstrates feasibility of using a procalcitonin-guided antibiotic treatment algorithm with AS audit and feedback in the PICU., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Antibiotic prescribing in ambulatory care centers is increasing. Previous research suggests that 20 to 50% of antibiotic prescriptions are either unnecessary or inappropriate. Unnecessary antibiotic consumption can harm patients by increasing antibiotic resistance and drug-associated toxicities, and the reasons for such use are multifactorial. Antimicrobial Stewardship Programs (ASP) were developed to guide better use of antibiotics. A core element of ASP is to provide feedback to clinical providers. To create clinically meaningful feedback, user-center design (UCD) is a robust approach to include end-users in the design process to improve systems., Objective: The study aimed to take a UCD approach to developing antibiotic prescribing feedback through input from clinicians in two ambulatory care settings., Methods: We conducted two group prototyping sessions with pediatric clinicians who practice in the emergency department and urgent care settings at a tertiary care children's hospital. Participants received background on the problem of antibiotic prescribing and then were interviewed about their information needs, perceived value, and desired incentives for a prescribing feedback system. Sessions concluded with their response and recommendations to sample sections of an antibiotic feedback report including orienting material, report detail, targeted education, and resources., Results: A UCD approach was found to be highly valuable in the development of a feedback mechanism that is viewed as desirable by clinicians. Clinicians preferred interpreting the data themselves with aids such as diagrams and charts over the researcher concluded statements about the clinician's behavior. Specific feedback that clinicians considered redundant were removed from the model if preexisting alerts were established., Conclusion: Integrating a UCD approach in developing ASP feedback identified desirable report characteristics that substantially modified preliminary wireframes for feedback. Future research will evaluate the clinical effectiveness of our feedback reports in outpatient settings., Competing Interests: None declared., (Thieme. All rights reserved.)

The prevalence of pediatric antimicrobial stewardship programs (ASPs) is increasing in acute care facilities across the United States. Over the past several years, the evidence base used to inform effective stewardship practices has expanded, and regulatory interest in stewardship programs has increased. Here, we review approaches for established, hospital-based pediatric ASPs to adapt and report standardized metrics, broaden their reach to specialized populations, expand to undertake novel stewardship initiatives, and implement rapid diagnostics to continue their evolution in improving antimicrobial use and patient outcomes.

Antimicrobial resistance is a global public health threat. Antimicrobial-resistant infections are on the rise and are associated with increased morbidity, mortality, and health care costs. Infants and children are affected by transmission of antimicrobial-resistant zoonotic pathogens through the food supply, direct contact with animals, environmental pathways, and contact with infected or colonized humans. Although the judicious use of antimicrobial agents is necessary for maintaining the health and welfare of humans and animals, it must be recognized that all use of antimicrobial agents exerts selective pressure that increases the risk of development of resistance. This report describes historical and recent use of antibiotics in animal agriculture, reviews the mechanisms of how such use contributes to development of resistance and can adversely affect child health, and discusses US initiatives to curb unnecessary use of antimicrobial agents in agriculture. [ABSTRACT FROM AUTHOR]

Background Acute otitis media (AOM) accounts for roughly 25% of antibiotics prescribed to children annually. Despite national guidelines that recommend short (5–7 days) durations of antibiotics for children 2 years and older with AOM, most receive long (10 day) courses. This study aims to evaluate antibiotic durations prescribed for children aged 2–17 years with uncomplicated AOM across two pediatric academic health systems, and to assess the variability in prescribed durations between and within each system. Methods Electronic medical record data from 135 care locations at two health systems were retrospectively analyzed. Outpatient encounters for children aged 2–17 years with a diagnosis of AOM from 2019 to 2022 were included. The primary outcome was the percent of 5-day prescriptions. Secondary outcomes included the proportion of 7-day prescriptions, 10-day prescriptions, prescriptions for nonfirst-line antibiotics, cases associated with treatment failure, AOM recurrence, and adverse drug events. Results Among 73 198 AOM encounters for children 2 years and older, 61 612 (84%) encounters resulted in an antibiotic prescription. Most prescriptions were for 10 days (45 689; 75%), 20% were for 7 days (12 060), and only 5% were for 5 days (3144). Treatment failure, AOM recurrence, adverse drug events, hospitalizations, and office, emergency department or urgent-care visits for AOM within 30 days after the index visit were rare. Conclusions Despite national guidelines that recommend shorter durations for children with uncomplicated AOM, 75% of our cohort received 10-day durations. Shortening durations of therapy for AOM could reduce antibiotic exposure and should be a priority of pediatric antibiotic stewardship programs. [ABSTRACT FROM AUTHOR]

Background The BioFire FilmArray Pneumonia Panel (BFPP), a multiplex PCR panel for the diagnosis of lower respiratory tract infections, has been proposed as a tool for antimicrobial stewardship. Few studies evaluate real-world implementation of the BFPP and no studies focus exclusively on children. Our institution implemented BFPP testing without restrictions. Methods We conducted a retrospective cohort study in children hospitalized at St. Louis Children's Hospital to (1) characterize the use of the BFPP in pediatric patients and (2) assess how results impacted antibiotic use. We included all BFPP tests obtained during the first year after the introduction of the test, September 2021 through August 2022. The primary outcome was change in antibiotic therapy within 24 hours of results, which was compared to the potential change in antibiotic therapy determined by two infectious diseases clinicians. Results One hundred sixty-nine tests from 126 patients were included. Nine patients were immunocompromised and 19 had chronic tracheostomy. The majority of tests were sent from tracheal aspirate specimens (92%) and from patients in an intensive care unit (94%). Only 51% of tests were obtained due to respiratory failure or suspected pneumonia. For 80% of test results, there was potential to change antibiotics, but change occurred in only 46% of tests in practice. Antibiotic escalation was more common (26%) than de-escalation (15%) or discontinuation (4.1%). Conclusions In a cohort of pediatric patients tested with the BFPP, the majority of tests were sent from tracheal aspirates and less than half of tests were associated with a change in antibiotics. [ABSTRACT FROM AUTHOR]

We conducted a national survey of pediatric infectious diseases (ID) clinicians on outpatient parenteral antibiotic therapy (OPAT) practices and post-discharge ID follow-up. Only 15% of sites required ID consultation for all OPAT. ID division resources for post-discharge care varied. Opportunities exist to increase ID involvement in post-discharge management of serious infections. [ABSTRACT FROM AUTHOR]

Background Reductions in the use of broad-spectrum antibiotics is a cornerstone of antimicrobial stewardship. We aim to demonstrate use of the Desirability of Outcome Ranking Approach for the Management of Antimicrobial Therapy (DOOR MAT) to evaluate the treatment of Escherichia coli and Klebsiella pneumoniae bloodstream infections in patients from the Veterans Health Administration (VHA) across a decade. Methods Using electronic records, we determined empiric and definitive antibiotic treatments, clinical characteristics, and 30-day mortality of patients with monomicrobial E. coli and K. pneumoniae bloodstream infections hospitalized in VHA medical centers from 2009 to 2018. Focusing on patients treated with parenteral β-lactams and with available antibiotic susceptibility testing results, we applied a range of DOOR MAT scores that reflect the desirability of antibiotic choices according to spectrum and activity against individual isolates. We report trends in resistance and desirability of empiric and definitive antibiotic treatments. Results During the 10-year period analyzed, resistance to expanded-spectrum cephalosporins and fluoroquinolones increased in E. coli but not in K. pneumoniae , while resistance to carbapenems and piperacillin-tazobactam remained unchanged. In 6451 cases analyzed, we observed improvements in DOOR MAT scores consistent with deescalation. Improvement in desirability of definitive treatment compared with empiric treatment occurred in 26% of cases, increasing from 16% in 2009 to 34% in 2018. Reductions in overtreatment were sustained and without negative impact on survival. Conclusions DOOR MAT provides a framework to assess antibiotic treatment of E. coli and K. pneumoniae bloodstream infections and can be a useful metric in antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Antimicrobial use (AU) in days of therapy per 1000 patient-days (DOT/1000 pd) varies widely among children's hospitals. We evaluated indirect standardization to adjust AU for case mix, a source of variation inadequately addressed by current measurements. Hospitalizations from the Pediatric Health Information System were grouped into 85 clinical strata. Observed to expected (O:E) ratios were calculated by indirect standardization and compared with DOT/1000 pd. Outliers were defined by O:E z -scores. Antibacterial DOT/1000 pd ranged from 345 to 776 (2.2-fold variation; interquartile range [IQR] 552–679), whereas O:E ratios ranged from 0.8 to 1.14 (1.4-fold variation; IQR 0.93–1.05). O:E ratios were moderately correlated with DOT/1000 pd (correlation estimate 0.44; 95% confidence interval, 0.19–0.64; P  = .0009). Using indirect standardization to adjust for case mix reduces apparent AU variation and may enhance stewardship efforts by providing adjusted comparisons to inform interventions. [ABSTRACT FROM AUTHOR]

Background Antibiotic use is common for acute respiratory infections (ARIs) in children, but much of this use is inappropriate. Few studies have examined whether rurality of residence is associated with inappropriate antibiotic use. We examined whether rates of ARI-related inappropriate antibiotic use among children vary by rurality of residence. Methods We conducted a retrospective cohort study of children aged 2 months–5 years enrolled in Tennessee Medicaid between 2007 and 2017 and diagnosed with ARI in the outpatient setting. Study outcomes included ARI, ARI-related antibiotic use, and ARI-related inappropriate antibiotic use. Multivariable Poisson regression was used to measure associations between rurality of residence, defined by the US Census Bureau, and the rate of study outcomes, while accounting for other factors including demographics and underling comorbidities. Results A total of 805 332 children met selection criteria and contributed 1 840 048 person-years (p-y) of observation. Children residing in completely rural, mostly rural, and mostly urban counties contributed 70 369 (4%) p-y, 479 121 (26%) p-y, and 1 290 558 p-y (70%), respectively. Compared with children in mostly urban counties (238 per 1000 p-y), children in mostly rural (450 per 1000 p-y) and completely rural counties (468 per 1000 p-y) had higher rates of inappropriate antibiotic use (adjusted incidence rate ratio [aIRR] = 1.34, 95% confidence interval [CI] = 1.33–1.35 and aIRR = 1.33, 95% CI = 1.32–1.35, respectively). Conclusions Inappropriate antibiotic use is common among young children with ARI, with higher rates in rural compared with urban counties. These differences should inform targeted outpatient antibiotic stewardship efforts. [ABSTRACT FROM AUTHOR]

Background. The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs. Methods. A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost. Results. Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost. Conclusions. rmPCR reported with templated comments reduced treatment of contaminants and use of broadspectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation. [ABSTRACT FROM AUTHOR]

Antimicrobial stewardship programs ( ASPs) are an effective strategy for improving the quality and safety of antimicrobial prescribing for hospitalized patients. Pediatric ASPs are in their early stages of development, and there are unique issues relevant to children. The imperative to ensure that antimicrobials are prescribed judiciously is highlighted by the ongoing epidemic increase in antimicrobial-resistant infections and the simultaneous decline in the rate of new drug development. In this review we describe the process of ASP development for pediatrics, review existing data regarding the impact of pediatric ASPs, and describe the priorities and challenges for ASP research including study design and appropriate end points. [ABSTRACT FROM AUTHOR]

Background Rapid blood culture diagnostics increase cost and have unclear benefit for patients with Gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, prospective randomized controlled trial (RAPIDS-GN), comparing outcomes of patients with GNB BSI who had blood culture testing with standard of care (SOC) culture and antibiotic susceptibility testing (AST) vs. rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno System (AXDX). Methods Subjects with blood culture Gram stain showing GNB were randomized to receive SOC testing with antimicrobial stewardship review (AS) or AXDX plus SOC testing with AS, at two academic medical centers between October 2017 and October 2018. SOC testing included rapid MALDI-TOF mass spectrometry ID and agar dilution or broth microdilution AST. In a modified intention to treat analysis, subjects were excluded if: Gram stain was erroneous, culture was positive during off-hours, blood culture in the prior week had GNB, they were deceased/on comfort care, or admitted to a nonparticipating hospital. The primary outcome was time to first antibiotic modification within 72 hours after randomization. Subjects without antibiotic modifications were assigned a time of 72 hours. No censoring was observed. T-tests and Wilcoxon rank-sum tests were used for statistical analyses. Results Of 500 randomized subjects, 448 were included (226 SOC, 222 AXDX). Groups did not differ in baseline characteristics (Table 1). Median (IQR) hours to first antibiotic modification was faster in the AXDX vs. SOC group [8.6 (2.6, 27.6) vs. 14.9 (3.3, 41.1)], P = 0.02 (Figure 1). Median (IQR) hours to first Gram-negative antibiotic modification (including escalation and de-escalation) was faster in the AXDX than SOC group [17.4 (4.9, 72) vs. 42.1 (10.1, 72)], P < 0.001 (Figure 2). Groups did not differ in clinical outcomes (Table 2). Mean (S.D.) time to results was faster for AXDX than SOC for organism ID [2.7 (1.2) h vs. 15.6 (20.3) h, P < 0.001] and AST [13 (55.7) h vs. 54.6 (45.5) h, P < 0.001]. Conclusion In the largest trial to evaluate the clinical impact of a blood culture diagnostic for GNB BSI, we found that rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for Gram-negative bacteremia. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant Robin Patel, MD, ASM and IDSA: Other Financial or Material Support, Travel reimbursement, editor's stipends; CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, Shionogi: Grant/Research Support; Curetis, Specific Technologies, NextGen Diagnostics, PathoQuest, Qvella: Consultant; NBME, Up-to-Date, the Infectious Diseases Board Review Course: Honorarium recipient, Other Financial or Material Support; Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued: Other Financial or Material Support, Patents. [ABSTRACT FROM AUTHOR]

Background Understanding patterns of inpatient antibiotic use is necessary to enhance appropriate use and minimize preventable harm at hospitals. Few studies have characterized antibiotic use in the inpatient setting in children. Methods We conducted a cross-sectional study in children admitted to 51 freestanding US children's hospitals included in the Pediatric Health Information System (PHIS). Overall and broad-spectrum antibiotic use (see Table) were measured using charge data, and prevalence of use was assessed on a single day of each 2017–2018 season over one year. Comparisons were made based on clinical setting (medical vs. surgical), clinical unit (PICU, NICU, and all others), hospital, and region. We assessed the relationship between antibiotic use and median hospital case-mix index (CMI), a surrogate for clinical complexity. Results Of 52769 hospitalized children assessed on a study day, 19174 (36%) received antibiotics, and 6575 (12%) received broad-spectrum antibiotics (table). Overall antibiotic use prevalence varied across hospitals from 22% to 52% (Figure 1). Median hospital CMI had no significant relationship with overall antibiotic use and only a weak correlation (ρ=0.29) with broad-spectrum antibiotic use (Figure 2). Antibiotic use prevalence varied minimally by season, ranging from 36% in fall to 37% in summer. Antibiotic use prevalence was 29% (9470/32436) among medical patients and 48% (9704/20333) among surgical patients. The antibiotics most commonly administered in medical patients were ceftriaxone and ampicillin, while surgical patients most commonly received cefazolin and vancomycin. Regional prevalence ranged from 33% (Midwest) to 40% (West). By unit, PICU patients had the highest prevalence of overall [58% (4006/6874)] and broad-spectrum [27% (1830/6874)] antibiotic use. Children with complex chronic conditions accounted for 63% of hospitalized children but represented 72% of children receiving any antibiotic and 85% of those receiving broad-spectrum antibiotics. Conclusion We observed large and apparently unexplained variability in antibiotic use prevalence among children's hospitals, clinical settings, and regions. This indicates potential opportunities for enhanced antibiotic stewardship activities. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant [ABSTRACT FROM AUTHOR]

Background Procalcitonin (PCT) testing enables earlier antibiotic (abx) de-escalation in adult intensive care units (ICUs); similar data in children are lacking. Methods Single-center pragmatic randomized controlled trial of children admitted to the pediatric ICU and started on intravenous (IV) abx February 2018–April 2019 to evaluate whether a PCT-guided testing and treatment algorithm implemented through antibiotic stewardship (AS) audit and feedback promotes abx de-escalation in the pediatric ICU. Patients were randomized by month to either control or PCT arm. Exclusion criteria were receipt of IV abx within 7 days prior to enrollment, immune compromise, neonates < 34 weeks gestation, or receipt of abx for an infection requiring prolonged abx. All subjects had baseline AS review. Subjects in the PCT arm had PCT testing on days 0, 1, 2, and 4 and AS guidance. Some subjects in the control arm had baseline PCT testing that was not available to providers. Abx de-escalation = stopping or narrowing spectrum of abx; Abx escalation = broadening spectrum or starting an additional abx. The primary outcome was abx days of therapy (DOT) per patient in the first 14 days after enrollment. Kruskal–Wallis, Chi-square, and ANOVA tests were used. Results The modified intention to treat analysis included 270 patients: 133 control and 137 PCT. Significantly more males and febrile patients were in the PCT-guided arm (Table 1). Overall, abx DOT did not differ between arms (Table 2). In 85 patients with pneumonia, median DOT per patient was shorter in the PCT than control arm (8.0 vs. 9.3 days, P = 0.04). Among patients in the PCT arm, those with initial PCT level > 0.5 mg/L (n = 93) (4.3 vs. 7.1 days, P = 0.006). More AS recommendations (recs) were made in the PCT arm (53 PCT vs. 35 control, P = 0.03). Compliance with AS recs was similar (70%) between arms. Conclusion In the pediatric ICU, the use of a PCT testing and treatment algorithm with AS audit and feedback resulted in shorter abx DOT for patients with pneumonia and more AS recs compared with no PCT testing. PCT testing implemented with AS can reduce abx duration in select populations of critically ill children. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant. [ABSTRACT FROM AUTHOR]