A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders.

BACKGROUND: Treatment of a child who has an anxiety disorder usually begins with the question of which treatment to start first, medication or psychotherapy. Both have strong empirical support, but few studies have compared their effectiveness head-to-head, and none has investigated what to do if the treatment tried first isn't working well-whether to optimize the treatment already begun or to add the other treatment. METHODS: This is a single-blind Sequential Multiple Assignment Randomized Trial (SMART) of 24 weeks duration with two levels of randomization, one in each of two 12-week stages. In Stage 1, children will be randomized to fluoxetine or Coping Cat Cognitive Behavioral Therapy (CBT). In Stage 2, remitters will continue maintenance-level therapy with the single-modality treatment received in Stage 1. Non-remitters during the first 12 weeks of treatment will be randomized to either [1] optimization of their Stage 1 treatment, or [2] optimization of Stage 1 treatment and addition of the other intervention. After the 24-week trial, we will follow participants during open, naturalistic treatment to assess the durability of study treatment effects. Patients, 8-17 years of age who are diagnosed with an anxiety disorder, will be recruited and treated within 9 large clinical sites throughout greater Los Angeles. They will be predominantly underserved, ethnic minorities. The primary outcome measure will be the self-report score on the 41-item youth SCARED (Screen for Child Anxiety Related Disorders). An intent-to-treat analysis will compare youth randomized to fluoxetine first versus those randomized to CBT first ("Main Effect 1"). Then, among Stage 1 non-remitters, we will compare non-remitters randomized to optimization of their Stage 1 monotherapy versus non-remitters randomized to combination treatment ("Main Effect 2"). The interaction of these main effects will assess whether one of the 4 treatment sequences (CBT➔CBT; CBT➔med; med➔med; med➔CBT) in non-remitters is significantly better or worse than predicted from main effects alone. DISCUSSION: Findings from this SMART study will identify treatment sequences that optimize outcomes in ethnically diverse pediatric patients from underserved low- and middle-income households who have anxiety disorders. TRIAL REGISTRATION: This protocol, version 1.0, was registered in ClinicalTrials.gov on February 17, 2021 with Identifier: NCT04760275 .

Diagnosis, microbial epidemiology, and antibiotic treatment of acute otitis media in children: a systematic review.

CONTEXT: Acute otitis media (AOM) is the most common condition for which antibiotics are prescribed for US children; however, wide variation exists in diagnosis and treatment. OBJECTIVES: To perform a systematic review on AOM diagnosis, treatment, and the association of heptavalent pneumococcal conjugate vaccine (PCV7) use with AOM microbiology. DATA SOURCES: PubMed, Cochrane Databases, and Web of Science, searched to identify articles published from January 1999 through July 2010. STUDY SELECTION: Diagnostic studies with a criterion standard, observational studies and randomized controlled trials comparing AOM microbiology with and without PCV7, and randomized controlled trials assessing antibiotic treatment. DATA EXTRACTION: Independent article review and study quality assessment by 2 investigators with consensus resolution of discrepancies. RESULTS: Of 8945 citations screened, 135 were included. Meta-analysis was performed for comparisons with 3 or more trials. Few studies examined diagnosis; otoscopic findings of tympanic membrane bulging (positive likelihood ratio, 51 [95% confidence interval {CI}, 36-73]) and redness (positive likelihood ratio, 8.4 [95% CI, 7-11]) were associated with accurate diagnosis. In the few available studies, prevalence of Streptococcus pneumoniae decreased (eg, 33%-48% vs 23%-31% of AOM isolates), while that of Haemophilus influenzae increased (41%-43% vs 56%-57%) pre- vs post-PCV7. Short-term clinical success was higher for immediate use of ampicillin or amoxicillin vs placebo (73% vs 60%; pooled rate difference, 12% [95% CI, 5%-18%]; number needed to treat, 9 [95% CI, 6-20]), while increasing the rate of rash or diarrhea by 3% to 5%. Two of 4 studies showed greater clinical success for immediate vs delayed antibiotics (95% vs 80%; rate difference, 15% [95% CI, 6%-24%] and 86% vs 70%; rate difference, 16% [95% CI, 6%-26%]). Data are absent on long-term effects on antimicrobial resistance. Meta-analyses in general showed no significant differences in antibiotic comparative effectiveness. CONCLUSIONS: Otoscopic findings are critical to accurate AOM diagnosis. AOM microbiology has changed with use of PCV7. Antibiotics are modestly more effective than no treatment but cause adverse effects in 4% to 10% of children. Most antibiotics have comparable clinical success.

Rapid Response and Code Events in Hospitalized Children on Home Mechanical Ventilation.

BACKGROUND: There is limited knowledge of rapid-response (RR) events and code events for children receiving home mechanical ventilation (HMV) via a tracheostomy in a non-ICU respiratory care unit. The purpose of this study was to describe the demographic and clinical factors leading to deterioration among these children and to identify the incidence and outcomes following rapid-response and code events. METHODS: A retrospective review was conducted on hospitalized HMV children who had RR/code events in a non-ICU respiratory care unit. RESULTS: There were a total of 50 RR events, and the primary clinical problem was acute respiratory distress, with 27 subjects (54%) needing ventilator adjustments. Twenty (40%) RR events occurred among children who were awaiting initial home discharge. Of 18 total code events, 7 (39%) children needed a tracheostomy-related intervention. There were 10 (56%) codes among children on mechanical ventilation awaiting initial home discharge. Children on HMV had 8.73 RR events per 1,000 patient days, whereas all other hospitalized children had 4.61 RR events per 1,000 patient days. In addition, children on HMV had 3.14 codes per 1,000 patient days, whereas all other hospitalized children had 0.74 codes per 1,000 patient days. All children were discharged from the hospital, and no deaths were associated with RR/code events for the index hospitalization. CONCLUSIONS: The overall incidence of RR/code events in children on HMV was higher than among non-HMV hospitalized children. Children on HMV preparing for their initial hospital discharge had the greatest number of RR/code events. The most prevalent interventions among children with RR events were ventilator setting adjustments, and among children with codes the most frequent actions were tracheostomy-related interventions. Developing strategies to predict risk factors for RR/code events may help decrease harm among children on HMV.

Sustaining and spreading the reduction of adverse drug events in a multicenter collaborative.

OBJECTIVES: Adverse drug events (ADEs) occur more frequently in pediatric patients than adults. ADEs frequently cause serious harm to children and increase the cost of care. The purpose of this study was to decrease ADEs by targeting the entire medication-delivery system for all high-risk medications. METHODS: Thirteen freestanding children's hospitals participated in this ADE collaborative. An advisory panel developed a change package of interventions that consisted of standardization of medication-ordering (eg, consensus-based protocols and order sets and high-alert medication protocols), reliable medication-dispensing processes (eg, automated dispensing cabinets and redesign of floor stock procedures), reliable medication-administration processes (eg, safe pump use and reducing interruptions), improvement of patient safety culture (eg, safety-culture changes and reduction of staff intimidation), and clinical decision support (eg, increase ADE detection and redesign care systems). ADE rates were compared from the 3-month baseline period to quarters of the 12-month intervention phase. ADE rates were categorized further as opioid related and other medication related. RESULTS: From baseline to the final quarter, the collaborative resulted in a 42% decrease in total ADEs, a 51% decrease in opioid-related ADEs, and a 41% decrease in other medication ADEs. CONCLUSION: A pediatric collaborative that targeted the medication-delivery system decreased the rate of ADEs at participating institutions.

Management of Acute Otitis Media: update.

CONTEXT: Acute Otitis Media (AOM), a viral or bacterial infection of the ear, is the most common childhood infection for which antibiotics are prescribed in the United States. In 2001, the Southern California Evidence-based Practice Center conducted a systematic review of the evidence comparing treatments of AOM. OBJECTIVES: This review updates the 2001 review findings on diagnosis and treatment of uncomplicated AOM, assesses the evidence for treatment of recurrent AOM, and assesses the impact of the heptavalent pneumococcal conjugate (PCV7) vaccine on the microbiology of AOM. DATA SOURCES AND STUDY SELECTION: Searches of PubMed® and the Cochrane databases were conducted from January 1998 to July 2010 using the same search strategies used for the 2001 report, with the addition of terms not considered in the 2001 review. The Web of Science was also searched for citations of the 2001 report and its peer-reviewed publications. DATA EXTRACTION: After review by two investigators against pre-determined inclusion/exclusion criteria, we included existing systematic reviews and randomized controlled clinical trials for assessment of treatment efficacy and safety. Pooled analysis was performed for comparisons with three or more trials. RESULTS AND CONCLUSIONS: Few studies were found that examined the accuracy and precision of the diagnosis of AOM. Since PCV7's introduction, AOM microbiology has shifted significantly, with Streptococcus pneumoniae becoming less prevalent and Haemophilus influenzae (HF) increasing in importance. For uncomplicated AOM, pooled analysis indicates that nine children (95% CI: 6, 20) would need to be treated with ampicillin or amoxicillin rather than placebo to note a difference in the rate of clinical success. However, in four studies of delayed treatment approaches for uncomplicated AOM, two had higher rates of clinical success with immediate antibiotic therapy while two did not, and in three studies, a marked decrease in antibiotic utilization was noted. We are unable to draw definitive conclusions regarding the comparative effectiveness of different antibiotics for AOM in children with recurrent otitis media (ROM). For ROM, long-term antibiotic administration will decrease AOM episodes from 3 to 1.5 for every 12 months of treatment per otitis prone child during active treatment (95% CI: 1.2, 2.1); however, potential consequences of long-term treatment need to be considered. Data were insufficient to draw conclusions about comparative effectiveness of different treatment strategies in subgroups of children with uncomplicated AOM. Adverse events were generally more frequent for amoxicillin-clavulanate than for cefdinir, ceftriaxone, or azithromycin. Higher quality studies and improved reporting of study characteristics related to quality are needed to provide definitive conclusions for AOM and ROM treatment options.

Characteristics of medication errors and adverse drug events in hospitals participating in the California Pediatric Patient Safety Initiative.

PURPOSE: The characteristics of medication errors and adverse drug events (ADEs) in hospitals participating in the California Pediatric Patient Safety Initiative (CaPPSI) were studied to identify opportunities for improvement. METHODS: Data were collected to identify pharmacy intervention medication errors (PIMEs) with significant harm potential and ADEs identified by a validated pediatric trigger method (TADEs) and by voluntary incident reports (VADEs) from November 2003 through April 2004. Electronic trigger identification was used. The primary outcomes measured were PIMEs, TADEs, and VADEs and the characteristics of these medication errors and ADEs. A secondary outcome measure was the positive predictive value of the trigger tool. RESULTS: The rates of PIMEs, TADEs, and VADEs were 2.67, 22.3, and 1.7 per 1000 patient days, respectively. PIMEs and ADEs occurred mostly among patients age one year or older during days 0 and 1 of admission and involved the following medication categories: antiinfectives and antibiotics, analgesics and antipyretics, and electrolytic-, caloric-, and water balance-replacement preparations. Most PIMEs involved an incorrect dosage or the wrong drug. Primary diagnoses differed between those with PIMEs and VADEs and those with TADEs. All medication processes were in need of improvement except dispensing. The trigger tool identified more ADEs than did voluntary incident reports by a factor of 11 and had a positive predictive value of 16.8%. CONCLUSION: Baseline rates of PIMEs, TADEs, and VADEs for pediatric hospitals in California were determined through collaborative efforts of CaPPSI facilities. Identification of ADEs was more effective when a trigger tool was used than when incidents were voluntarily reported.

Development, testing, and findings of a pediatric-focused trigger tool to identify medication-related harm in US children's hospitals.

OBJECTIVES: The purposes of this study were to develop a pediatric-focused tool for adverse drug event detection and describe the incidence and characteristics of adverse drug events in children's hospitals identified by this tool. METHODS: A pediatric-specific trigger tool for adverse drug event detection was developed and tested. Eighty patients from each site were randomly selected for retrospective chart review. All adverse drug events identified using the trigger tool were evaluated for severity, preventability, ability to mitigate, ability to identify the event earlier, and presence of associated occurrence report. Each trigger and the entire tool were evaluated for positive predictive value. RESULTS: Review of 960 randomly selected charts from 12 children's hospitals revealed 2388 triggers (2.49 per patient) and 107 unique adverse drug events. Mean adverse drug event rates were 11.1 per 100 patients, 15.7 per 1000 patient-days, and 1.23 per 1000 medication doses. The positive predictive value of the trigger tool was 3.7%. Twenty-two percent of all adverse drug events were deemed preventable, 17.8% could have been identified earlier, and 16.8% could have been mitigated more effectively. Ninety-seven percent of the identified adverse drug events resulted in mild, temporary harm. Only 3.7% of adverse drug events were identified in existing hospital-based occurrence reports. The most common adverse drug events identified were pruritus and nausea, the most common medication classes causing adverse drug events were opioid analgesics and antibiotics, and the most common stages of the medication management process associated with preventable adverse drug events were monitoring and prescribing/ordering. CONCLUSIONS: Adverse drug event rates in hospitalized children are substantially higher than previously described. Most adverse drug events resulted in temporary harm, and 22% were classified as preventable. Only 3.7% were identified by using traditional voluntary reporting methods. Our pediatric-focused trigger tool is effective at identifying adverse drug events in inpatient pediatric populations.

An intervention to decrease narcotic-related adverse drug events in children's hospitals.

OBJECTIVES: Narcotic-related adverse drug events are the most common adverse drug events in hospitalized children. Despite multiple published studies describing interventions that decrease adverse drug events from narcotics, large-scale collaborative quality improvement efforts to address narcotic-related adverse drug events in pediatrics have not been described. The purpose of this study was to evaluate collaborative-wide narcotic-related adverse drug event rates after a collection of expert panel-defined best practices was implemented. METHODS: All 42 children's hospitals in the Child Health Corporation of America were invited to participate in the Institute for Healthcare Improvement-style quality improvement collaborative aimed at reducing narcotic-related adverse drug events. A collection of interventions known or suspected to reduce narcotic-related adverse drug events was recommended by an expert panel, with each site implementing >or=1 of these best practices on the basis of local need. Narcotic-related adverse drug event rates were compared between the baseline (December 1, 2004, to March 31, 2005) and postimplementation periods (January 1, 2006, to March 31, 2006) after an a priori-defined intervention ramp-up time (April 1, 2005, and December 31, 2005). Secondary outcome measures included constipation rates and narcotic-related automated drug-dispensing-device override percentages. RESULTS: Median narcotic-related adverse drug event rates decreased 67% between the baseline and postimplementation time frames across the 14-site collaborative. Constipation rates decreased 68.9%, and automated drug-dispensing-device overrides decreased from 10.18% to 5.91% of all narcotic doses administered. CONCLUSIONS: Implementation of >or=1 expert panel-recommended interventions at each participating site resulted in a significant decrease in narcotic-related adverse drug events, constipation, and automated drug-dispensing-device overrides in a 12-month, 14-site children's hospital quality collaborative.

Toward transparent clinical policies.

Clinical policies of professional societies such as the American Academy of Pediatrics are valued highly, not only by clinicians who provide direct health care to children but also by many others who rely on the professional expertise of these organizations, including parents, employers, insurers, and legislators. The utility of a policy depends, in large part, on the degree to which its purpose and basis are clear to policy users, an attribute known as the policy's transparency. This statement describes the critical importance and special value of transparency in clinical policies, guidelines, and recommendations; helps identify obstacles to achieving transparency; and suggests several approaches to overcome these obstacles.

Evidence assessment of the accuracy of methods of diagnosing middle ear effusion in children with otitis media with effusion.

OBJECTIVES: We report the findings of an evidence assessment on the accuracy of methods of diagnosing middle ear effusion in children with otitis media with effusion (OME). METHODS: We searched Medline (1966-January 2000), the Cochrane Library (through January 2000), and Embase (1980-January 2000) and identified additional articles from reference lists in proceedings, published articles, reports, and guidelines. Excluded were nonhuman studies; case reports; editorials; letters; reviews; practice guidelines; non-English-language publications; and studies on patients with immunodeficiencies, craniofacial anomalies (including cleft palate), primary mucosal disorders, or genetic conditions. From each eligible study, we calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and prevalence of OME in the cohort. We determined the number of studies for each comparison of a diagnostic method and a reference standard listed within the scope of our assessment. For comparisons with 3 or more studies, we derived random effects estimates of sensitivity, specificity, and prevalence rate. Using the pooled estimates, we plotted the performance of each diagnostic test in terms of sensitivity and (1 - specificity) and identified the best performer among the tests included in the comparison. RESULTS: Among 8 diagnostic methods, pneumatic otoscopy had the best apparent performance with a sensitivity of 94% (95% confidence interval: 92%-96%) and a specificity of 80% (95% confidence interval: 75%-86%). However, examiner qualifications were reported inconsistently, and training was not specified. CONCLUSIONS: The finding that pneumatic otoscopy can do as well as or better than tympanometry and acoustic reflectometry has significant practical implications. For the typical clinician, pneumatic otoscopy should be easier to use than other diagnostic methods. The important question may be what degree of training will be needed for the clinician to be as effective with pneumatic otoscopy as were the examiners in the studies reviewed in this report.