40 TH ANNUAL PEDIATRICS IN THE RED ROCKS CONFERENCE

S A M U E L F L O R E S , M D – P E D I A T R I C H O S P I T A L I S T ,

K I D S L I N K H O S P I T A L I S T G R O U P , P H O E N I X C H I L D R E N ’ S H O S P I T A L

B R I T T A N Y W O L D M D – P E D I A T R I C H O S P I T A L I S T F E L L O W , K I D S L I N K H O P S I T A L I S T G R O U P , P H O E N I X

C H I L D R E N ’ S H O S P I T A L

T E R E S A B L A S K O V I C H – P L 3 P E D I A T R I C R E S I D E N T , P C H / M M C R E S I D E N C Y P R O G R A M

S A R A H F R A N C I X – P L 2 P E D I A T R I C R E S I D E N T , P C H / M M C

R E S I D E N C Y P R O G R A M

W H I T N E Y G U T I E R R A Z – P L 2 P E D I A T R I C R E S I D E N T , P C H / M M C R E S I D E N C Y P R O G R A M

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Disclosure

We have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in the CME activity.

We do not intend to discuss an unapproved/investigative use of a commercial product/device in our presentation.

Literature Review

Journals

Journal of Pediatrics

Journal of Pediatric Infectious Diseases

Journal of Pediatric Gastroenterology

Journal of Hospital Pediatrics

A L E X A N D E R W . H I R S C H , M D , M I C H A E L C . M O N U T E A U X , S C D , G E N N A F R U C H T M A N , B A , R I C H A R D G . B A C H U R ,

M D , M A R K I . N E U M A N , M D , M P H

H O S P I T A L P E D I A T R I C S V O L 1 3 8 , I S S U E 2 , A U G U S T 2 0 1 6

Characteristics of Children Hospitalized with Aspiration

Pneumonia

Case

Aspiration Pneumonia

Aspiration pneumonia is an infectious process due to the aspiration of pharyngeal secretions that are colonized by pathogenic bacteria.

It is an important cause of serious morbidity and mortality, particularly among children with chronic medical conditions

Pathophysiology and Bacteriology

A study revealed that half of all healthy adults aspirate small amounts of oropharyngeal secretions during sleep.

There are multiple protective mechanisms to prevent aspiration: During aspiration the airway is exposed to oropharyngeal saliva or

acidic gastric contents, along with enteric bacteria. Traditionally been attributed to anaerobic bacteria. Brook I, Finegold SM. Bacteriology of aspiration pneumonia in children. Pediatrics. 1980;65(6):1115–1120 Average of 5 bacteria isolated per specimen with a mixture of anaerobes and

aerobes.

Conditions that increase the volume of aspirated oropharyngeal contents lead to an increased risk of aspiration pneumonia. Reduced level of consciousness: chronic neurological impairment, seizure,

anesthesia, alcohol or substance abuse Dysphagia Gastroesophageal reflux Foreign body aspiration Use of a NG tube

Objective

Study Aim: To evaluate the difference in disease entities (aspiration pneumonia vs CAP) in regards to:

Patient characteristics: median age, sex, race, proportion of patients with a complex chronic condition (CCC).

Hospitalization characteristics: length of stay, ICU admission, cost, 30-day readmission rate, and median hospitalization costs.

Pharmacological treatment: antibiotics or corticosteroid administration.

Seasonal variability

Methods

Retrospective cohort study

Pediatric Health Information System: administrative database that contains encounter-level data from more than 47 tertiary care pediatric hospitals.

Inclusion Criteria: discharged from inpatient or observation with a diagnosis of aspiration pneumonia or CAP between 1/2009 – 12/2014.

Exclusion Criteria: Children with cystic fibrosis and children who died during their hospitalization.

Methods – Further Classification

Proportion of patient’s with complex chronic conditions Dx expected to last > 12 months Involve several organ systems or 1 organ system severely

enough to require specialty care and hospitalization. Presence of technology dependence: gastrostomy,

tracheostomy, cerebrospinal fluid ventricular shunt, permanent indwelling catheter and pacemaker.

ICD-9 diagnosis codes for complicated pneumonia and related procedures.

Illness severity (measured using the severity scale defined as part of the All Patient Refined Diagnosis Related Groups Classification).

Results: Demographics

Exclusion: CF (7723) and children that died during the hospitalization (623) Mortality was more likely among

children with aspiration pneumonia. (1.6% vs 0.4%, P < 0.001).

Children with aspiration pneumonia were older and more likely to have public insurance than children with CAP.

Results: comorbidities

Children with aspiration pneumonia where more likely to have a CCC and more likely to have multiple chronic conditions.

54.8% of children with aspiration pneumonia had a neurological comorbidity compared with 10% of children with CAP.

Most common type of chronic condition: technology dependence.

Results

Aspiration pneumonia was associated with: Longer median hospital length

of stay (5 days vs 2 days). Hospitalization > 1 week. 3 times as likely to require ICU

care (33% vs 12%).

Hospital readmission within 30 days occurred in 36% of patients (vs 16%)

Median cost of hospitalization was $14,963 vs $6,115 for CAP.

Results

Controlling for confounding variables:

Analyses were performed between children with aspiration pneumonia vs CAP without complex chronic conditions.

Aspiration pneumonia continued to have:

Longer hospital stays (3 vs 2 days, P < .001).

More likely to require ICU admission ( 22.9% vs 7.4%, P < .001).

Higher median hospital costs ($8127 vs $4793, P < .001).

Results: Pharmacological Treatment

Antibiotic prescribing patterns differed between children hospitalized with aspiration pneumonia and those with CAP.

Results: Seasonal Variation

Discussion

Children with aspiration pneumonia are hospitalized for longer durations of time, have higher rates of mortality, more likely to require ICU level care and have higher 30-day readmission rates

These differences reflect different disease processes but are also reflective of vastly different patient populations.

Patients with aspiration pneumonia are more likely to have complex chronic conditions.

Antibiotic strategies reflect an attempt to capture the different microbial profiles that distinguish CAP from aspiration pneumonia.

Strengths and Limitations

Strengths Large population Secondary analysis performed that was restricted to children

without complex chronic conditions. Statistically significant differences were determine between the

two groups. Limitations Misclassification of patients

There is little clinical information available in the Pediatric Health Information System administrative database.

Does not demonstrate a generalized population. Only examined inpatient encounters. Likely inherent bias in the labeling of a diagnosis of aspiration in a

child with a chronic condition. Treatment initiation and duration.

Conclusion

This study supplements a growing body of literature suggesting health outcomes are worse and hospital resources use is higher in patient’s diagnosed with aspiration verses non-aspiration pneumonia.

There needs to be further research to improve coordination of care and treatment of children at risk for aspiration pneumonia.

B O R J A G O M E Z , M D , A , B S A N T I A G O M I N T E G I , M D , P H D , A , B S I L V I A B R E S S A N , M D , P H D , C L I V I A N A D A D A L T ,

M D , D A L A I N G E R V A I X ,

M D , E L A U R E N C E L A C R O I X , M D

J O U R N A L O F P E D I A T R I C S , V O L U M E 1 3 8 , N U M B E R 2 , A U G U S T 2 0 1 6

Validation of the “Step-by-Step” Approach in the Management of

Young Febrile Infants

Objective

Prospectively validate the Step-by-Step approach

Compare it to the Rochester criteria and the Lab-score for identifying low risk febrile infants

Why do we Care?

National ongoing goal (Project REVISE) to differentiate high vs low risk febrile infants

Reduce risk of procedures (LP)

Reduce risk of unnecessary antibiotic exposure

Reduce length of hospitalization

Reduce healthcare costs

Study Design

Multicenter Study: 11 European pediatric emergency departments

Infants ≤ 90 days old presenting with fever without a source

September 2012 – August 2014

Study Design

Urine dipstick, urine culture, WBC, CRP, PCT, and blood culture were collected on every patient

Further testing, treatment, and admission at discretion of attending physician

Step-by-Step, Rochester criteria, and Lab-score were applied to each patient and compared

Exclusion Criteria

1. Clear source of fever identified after a careful medical history

2. No fever on arrival at the PED and fever that had only been subjectively assessed by parents on touch, without the use of a thermometer

3. Absence of 1 or more of the mandatory ancillary tests (blood culture, urine culture collected by an aseptic technique, urine dipstick, PCT, CRP, or WBC count)

4. Refusal of the parents or caregiver to participate

Rochester Criteria

Infant appears well

Infant is previously healthy

Term, no perinatal/postnatal antibiotics, no hospitalizations, no chronic illness, no unexplained hyperbilirubinemia)

No evidence of skin, soft tissue, bone, joint or ear infection

Labs:

WBC 5,000 – 15,000

Bands </= 1,500

</= 10 WBC on urine microscopy

</= 5 WBC on stool microscopy if diarrhea

Lab-Score criteria

Assigns points for pro-calcitonin, CRP, and UA

Step-By-Step

Results

Discussion

The Step by Step approach was the most accurate at ruling out an invasive bacterial infection.

High sensitivity

High NPV

Best negative LR

Due to the low prevalence of IBI, the specificity, PPV, and positive LR were poor for all 3 approaches

Missed IBI’s

6 of the 7 invasive bacterial infections missed by the Step by Step approach, had fever duration of less than 2 hours

Conclusions

Step-by-Step approach appears to be a useful tool for risk stratifying febrile infants.

Caution should be used in infants with very short fever duration. These infants may require additional observation.

J E F F R E Y R I E S E , M D , A T I M O T H Y P O R T E R , M D , A J A M I E F I E R C E , M D , A A L I S O N R I E S E , M D , M P H , A T R O Y

R I C H A R D S O N , M S , M P H , P H D , B B R I A N K . A L V E R S O N , M D A

J O U R N A L O F H O S P I T A L P E D I A T R I C S , V O L U M E 7 , I S S U E 4 , A P R I L 2 0 1 7

Clinical Outcomes of Bronchiolitis After Implementation of a General Ward High

Flow Nasal Cannula Guideline

Study Question

Is there an association between using high-flow nasal cannula on general wards and clinical outcomes of infants with bronchiolitis?

Study Design

Retrospective, interrupted time series analysis of pre and post-implementation of HFNC guideline

Hasbro Children’s Hospital (tertiary center in Providence, RI)

Allowed admission to floor on HFNC

Allowed initiation of HFNC on floor patient

Allowed transfer of PICU to floor on HFNC

Patient Selection

Inclusion:

Infants <24 months admitted from 2010 – 2014 with bronchiolitis

Exclusion:

<37 weeks prematurity

CLD, asthma, heart disease, neurologic disease, chromosomal abnormalities

Admitted >21 days

Clinical Outcomes

Primary Outcome: Hospital length of stay

Secondary Outcome:

PICU transfer from wards

PICU length of stay

Adverse outcomes (intubation and 30 day readmission)

Study Results

Looked at unadjusted vs adjusted clinical outcomes

Adjusted = takes into account pre-intervention trends of improvement in bronchiolitis management

Days of HFNC

LOS – All patients with Bronchiolitis

LOS – Patients receiving HFNC

LOS – Patients not receiving HFNC

PICU Length of Stay

Transfer rate to PICU

Author’s Conclusions

Implementing use of HFNC on general ward was associated with increase in use, but no significant changes in measured clinical outcomes of bronchiolitis

Study Limitations

Did the guideline actually change practice? Despite claim that use of HFNC increased, there is

no adjusted data on patients who “Received any HFNC therapy”

Interrupted time series can be difficult to interpret when it takes time for change to actually come into effect

Interrupted time series requires extrapolation of data

Inability to control confounding variables Hospital LOS calculated in whole days

J O E L S . T I E D E R , M D , M P H , F A A P , J O S H U A L . B O N K O W S K Y , M D , P H D , F A A P , R U T H A . E T Z E L , M D , P H D , F A A P , W A Y N E , H . F R A N K L I N , M D , M P H , M M M ,

F A A P , D A V I D A . G R E M S E , M D , F A A P , B R U C E H E R M A N , M D , F A A P , E L I O T S . K A T Z , M D , F A A P , L E O N A R D R .

K R I L O V , M D , F A A P , J . L A W R E N C E M E R R I T T I I , M D , F A A P , C H U C K N O R L I N , M D , F A A P , J A C K P E R C E L A Y , M D ,

M P H , F A A P , R O B E R T E . S A P I E N , M D , M M M , F A A P , R I C H A R D N . S H I F F M A N , M D , M C I S , F A A P , M I C H A E L

B . H . S M I T H , M B , F R C P C H , F A A P

J O U R N A L O F P E D I A T R I C S V O L U M E 1 3 7 , N U M B E R 5 , M A Y 2 0 1 6 :

What are the Clinical Practice Guidelines for Brief Resolved Unexplained Events(BRUE)?

ALTE

ALTE originated from 1986 National Institutes of Health Consensus Conference on Infantile Apnea

Intended to replace “Near-miss sudden infant death syndrome”

ALTE: episode that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking, or gagging

BRUE

BRUE:

Occurs in infants < 1 year of age when the observer reports a sudden, brief, and now resolved episode of >1 of the following:

Cyanosis or pallor

Absent, decreased, or irregular breathing

Marked change in tone (hypertonia or hypotonia)

Altered level of consciousness

Diagnose a BRUE only when there is no explanation for a qualifying event after conducting an appropriate history and physical examination

History Considerations

Considerations for child abuse

History of the event

State during the event

End of event

State after event

Recent history

Past medical history

Family history

Environmental history

Social history

Physical Exam Considerations

General appearance Growth variables Vital signs Skin HEENT Neck Chest Heart Abdomen Genitalia Extremities Neurologic

Lower Risk Group

Age > 60 days

Gestational age > 32 weeks and post-conceptional age > 45 weeks

First BRUE

Duration of event < 1 minute

No CPR required by trained medical provider

No concerning historical features

No concerning physical examination findings

Methods

A multidisciplinary subcommittee including doctors, methodologist, epidemiologist and parent representatives performed a systematic review of literature of ALTEs from 1970-2014

Evidence-based recommendations were graded based on benefit vs. harm

Key Action Statement: Cardiopulmonary

Clinicians need not admit infants presenting with a lower risk BRUE to the hospital solely for cardiorespiratory monitoring (Grade B, Weak Recommendation)

Clinicians may briefly monitor infants presenting with a lower risk BRUE with continuous pulse oximetry and serial observations (Grade D, Weak Recommendation)

Clinicians should not obtain a chest radiograph in infants presenting with a lower risk BRUE (Grade B, Moderate Recommendations)

Clinicians should not obtain measurement of venous or arterial blood gases in infants presenting with a lower-risk BRUE (Grade B, Moderate Recommendation)

Key Action Statement: Cardiopulmonary Cont.

Clinicians should not obtain an overnight polysomnograph in infants presenting with Lower-Risk BRUE (Grade B, Moderate Recommendation)

Clinicians may obtain a 12-lead electrocardiogram for infants presenting with lower-risk BRUE (Grade C, Weak Recommendation)

Clinicians should not obtain an echocardiogram in infants presenting with lower-risk BRUE (Grade C, Moderate Recommendation)

Clinicians should not initiate home cardiorespiratory monitoring in infants presenting with a lower-risk BRUE (Grade B, Moderate Recommendations)

Key Action Statement: Child Abuse

Clinicians need not obtain neuroimaging (computed tomography, MRI, or ultrasonography) to detect child abuse in infants presenting with a lower-risk BRUE (Grade C, Weak Recommendation)

Clinicians should obtain an assessment of social risk factors to detect child abuse in infants presenting with a lower-risk BRUE (Grade C, Moderate Recommendation)

Child Abuse History and Physical

History: Developmentally inconsistent or discrepant history provided by the caregivers, a previous ALTE, a recent emergency service telephone call, vomiting, irritability, or bleeding from nose or mouth

Social risk factors: unrealistic expectations, mental health problems, domestic violence/intimate partner violence, social service involvement, law enforcement involvement, and substance abuse

Physical exam: large or full/bulging anterior fontanel, scalp bruising or bogginess, oropharynx, frenula damage, skin findings such as bruising or petechiae

Key Action Statement: Neurology

Clinicians should not obtain neuroimaging (computed tomography, MRI, or ultrasonography) to detect neurologic disorders in infants presenting with a lower-risk BRUE (Grade C, Moderate Recommendation)

Clinicians should not obtain an EEG to detect neurologic disorders in infants presenting with a lower-risk BRUE (Grade C, Moderate Recommendation)

Clinicians should not prescribe antiepileptic medications for potential neurologic disorders in infants presenting with a lower-risk BRUE (Grade C, Moderate Recommendation)

Key Action Statement: Infectious Disease

Clinicians should not obtain a white blood cell count, blood culture, or cerebrospinal fluid analysis or culture to detect an occult bacterial infection in infants presenting with a Lower-Risk BRUE (Grade B, Strong Recommendation)

Clinicians need not obtain a urinalysis (bag or catheter) in infants presenting with a Lower Risk BRUE (Grade C, Weak Recommendation)

Clinicians should not obtain a chest radiograph to assess for pulmonary infection in infants presenting with a Lower-Risk BRUE (Grade B, Moderate Recommendation)

Key Action Statement: Infectious Disease Cont.

Clinicians need not obtain respiratory viral testing if rapid testing is available in infants presenting with a Lower-Risk BRUE (Grade C, Weak Recommendations)

Clinicians may obtain testing for pertussis in infants presenting with a Lower-Risk BRUE (Grade B, Weak Recommendation)

Key Action Statement: Gastroenterology

Clinicians should not obtain investigations for GER (eg. Upper Gastrointestinal Series, pH probe, Endoscopy, Barium Contrast Study, Nuclear Scintigraphy, and Ultrasonography) in infants presenting with a Lower-Risk BRUE (Grade C, Moderate Recommendation)

Clinicians should not prescribe acid suppression therapy for infants presenting with a Lower-Risk BRUE (Grade C, Moderate Recommendation)

Key Action Statement: Inborn Errors of Metabolism

Clinicians need not obtain measurements in lower-risk BRUE:

Serum lactic Acid

Serum bicarbonate

Electrolytes

Calcium

Ammonia

Venous or arterial blood gases

Blood glucose

Urine organic acids, plasma amino acids, or plasma acylcarnitines

Key Action Statement: Anemia

Clinicians should not obtain laboratory evaluation for anemia in infants presenting with a Lower-Risk BRUE (Grade C, Moderate Recommendation)

Key Action Statement: Patient-and Family-Centered Care

Clinicians should offer resources for CPR training to caregivers (Grade C, Moderate Recommendation)

Clinicians should educate caregivers about BRUEs (Grade C, Moderate Recommendation)

Clinicians should use shared decision-making for infants presenting with a Lower-Risk BRUE (Grade C, Moderate Recommendation)

Conclusion

Efforts and education needed to facilitate BRUE guideline across medical community

Guideline created to give physicians definition and appropriate work-up given many situations.

Further research required to determine incidence of BRUEs and effective of BRUE definition

A L E X A N D E R W . H I R S C H , M D , M I C H A E L C . M O N U T E A U X , S C D , G E N N A F R U C H T M A N , B A , R I C H A R D G . B A C H U R , M D ,

M A R K I . N E U M A N , M D , M P H

H O S P I T A L P E D I A T R I C S V O L U M E 6 , I S S U E 1 1 , N O V E M B E R 2 0 1 6

Are Proton Pump Inhibitors Effective for Treating GERD in

Infants Ages 1-11 months?

GER: A Physiological Manifestation

Gastroesophageal reflux (GER) defined as retrograde passage of gastric contents into the esophagus or extra-esophageal regions

Associated with transient relaxation of the lower esophageal sphincter

Typically presents as recurrent vomiting or persistent regurgitation

When GER Becomes Pathological

Physiological GER can become pathologic when it produces adverse symptoms or histologic and/or endoscopic visible changes

Clinical symptoms: Recurrent vomiting

Poor weight gain

Irritability

Dysphagia

Discomfort

Esophagitis

Respiratory Disorders

Goal of Study

Evaluate the efficacy and safety of esomeprazole in infants ages 1-11 months with signs and symptoms of GERD.

Methods

Randomized, double-blind, placebo-controlled parallel-group, treatment-withdrawal study conducted in 33 centers in the United States, France, Germany, and Poland

A 2-week open-label treatment phase followed by a 4-week randomized, double-blind, placebo-controlled treatment phase

Study Design

During 2-week open-label phase, all patients received esomeprazole once daily dosed per weight

After open-label phase, infants were randomized 1:2 to double-blind treatment with esomeprazole (at the open-label dose) or placebo for up to 4 weeks

Methods: Assessments

Primary efficacy endpoint was time from randomization to discontinuation owing to symptoms worsening in double-blind phase.

Secondary endpoints included time from randomization to discontinuation for any reason, proportion of patients achieving treatment success, daily symptoms assessed by parent/guardian, and PGA symptom severity

Safety and tolerability also evaluated through recording of adverse events

Results: Double-Blind Treatment Open-Label Phase

Results: Double-blind Treatment Withdrawal Phase

Primary analysis: Discontinuation from study secondary to symptom worsening in placebo group 48.8% (20/41 patient) compared with 38.5% (15/39) patients who received esomeprazole

No statistical significance (HR 0.69%, 95% CI 0.35-1.35%, P=0.28) but numerically favored esomeprazole group

More infants in placebo (n=17) than in the esomeprazole group (n=10) discontinued from the study

Results: Safety and Tolerability

In open-label phase, 47 of 98 patients (48%) had adverse events; 4 patients (4.1%) considered treatment related

During the double-blind phase, 23 of 39 (59%) of esomeprazole-treated patients and 27 of 41 (66%) of placebo patients had adverse events

Discussion

Patients treated with esomeprazole had a 31% reduced risk of discontinuing from the study owing to worsening of symptoms compared with infants who received placebo. No statistical difference.

Most infants (83%) had improvement of GERD symptoms within 2 weeks of starting open-label esomeprazole therapy

Discussion: Limitations

Inclusion of mixed-type study population

Patients with a variety of symptoms enrolled

No assessment of time to symptom resolution during the open-label phase

No insight as to whether patients who improved during the open-label phase would have improved with or without treatment

Discussion: Summary

No statistically significant difference between PPI treatment and placebo

Infants with more severe symptoms and confirmed GERD may benefit more from PPI therapy

No clinical studies of infants < 1 year old have demonstrated a statistical benefit in treating with PPIs

PPIs are well tolerated by infants

Discussion: Future Research

PPIs and their role in treating infants < 1 year old with severe disease symptoms and confirmed GERD

Clarification in identifying patients most likely to respond favorably to PPIs