The Uniformed Services Constipation Action Plan: An Effective Tool for the Management of Children with Functional Constipation.

OBJECTIVE: To implement and to evaluate the effectiveness of the Uniformed Services Constipation Action Plan (USCAP) in our gastroenterology clinic for children with functional constipation. STUDY DESIGN: This implementation science study included toilet-trained subjects aged 4 years and older who met the Rome IV criteria for functional constipation. Children were block randomized to receive either the USCAP or control. All clinic functional constipation plans recommended subjects continue pharmacotherapy for 4 months. Endpoints measured were clinical outcomes (resolution of functional constipation and achievement of a Pediatric Bristol Stool Form Scale [PBSFS] score of 3 or 4), patient-related outcomes (health-related quality of life [HRQoL] total scale score), and health confidence outcomes (Health Confidence Score [HCS]). RESULTS: Fifty-seven treatment group subjects (44%) received a USCAP (52% male; mean age, 10.9 [4.9] years) compared with 73 controls (56%; 48% male; mean age,10.9 [5.3] years). A PBSFS score of 3 or 4 was achieved by 77% of the treatment group compared with 59% of controls (P = .03). Subjects from the treatment group were more likely than the controls to endorse adherence to the 4-month course of pharmacotherapy (P < .001). Subjects who received a USCAP had greater improvements in HRQoL total scale score by the end of the project (P = .04). CONCLUSIONS: The USCAP is a simple, inexpensive tool that has the potential to improve global outcomes for functional constipation in children and should be recommended as standard clinical practice.

Acid Suppression and Antibiotics Administered during Infancy Are Associated with Celiac Disease.

OBJECTIVE: To investigate why certain at-risk individuals develop celiac disease (CD), we examined the association of proton pump inhibitors (PPI), histamine-2 receptor antagonists (H2RAs), and antibiotic prescriptions in the first 6 months of life with an early childhood diagnosis of CD. STUDY DESIGN: A retrospective cohort study was performed using the Military Healthcare System database. Children with a birth record from October 1, 2001, to September 30, 2013, were identified. Outpatient prescription records were queried for antibiotic, PPI, and H2RA prescriptions in the first 6 months of life. Cox proportional hazards regression was used to calculate the hazard ratio (HR) of developing CD based on medication exposure. International Classification of Diseases, Ninth Revision, Clinical Modification codes identified children with an outpatient visit for CD. RESULTS: There were 968 524 children who met the inclusion criteria with 1704 cases of CD in this group. The median follow-up for the cohort was approximately 4.5 years. PPIs (HR, 2.23; 95% CI, 1.76-2.83), H2RAs (HR, 1.94; 95% CI, 1.67-2.26), and antibiotics (HR, 1.14; 95% CI, 1.02-1.28) were all associated with an increased hazard of CD. CONCLUSIONS: There is an increased risk of developing CD if antibiotics, PPIs and H2RAs are prescribed in the first 6 months of life. Our study highlights modifiable factors, such as medication stewardship, that may change the childhood risk of CD.

Association of Early Life Prescriptions for Antibiotics and Acid Suppressants with Childhood Psychotropic Prescriptions.

OBJECTIVE: To examine the association between antibiotic and acid suppressant prescriptions in the first 2 years of life and subsequent treatment for childhood psychiatric disorders. STUDY DESIGN: This was a retrospective cohort study of children born between October 2001 and September 2012 in the Military Health System enrolled in TRICARE past age 2 years and within 35 days of birth, with an initial hospital stay <7 days, and without psychotropic agents dispensed during the first 2 years of life. Exposure was defined as a filled prescription for an antibiotic or acid suppressant before age 2 years, and the outcome was defined as a filled prescription for a psychotropic agent after age 2 years. RESULTS: For the 804 920 patients (51% males and 49% female) composing the study population, the mean age at first psychotropic prescription was 6.8 years. A total of 24 176 children (3%) were prescribed a proton pump inhibitor (PPI), 79 243 (10%) were prescribed a histamine-2 receptor antagonist (H2RA), and 607 348 (76%) were prescribed an antibiotic during the first 2 years of life. The adjusted hazard ratio (aHR) of a psychotropic prescription was significantly increased in children prescribed any H2RA (1.79; 95% CI, 1.63-1.96), PPI (1.47; 95% CI, 1.26-1.71), or antibiotic (1.71; 95% CI, 1.59-1.84). The aHR of psychotropic prescriptions increased commensurately with each additional antibiotic class added and with each additional class of medication (H2RA, PPI, or antibiotics) prescribed. CONCLUSIONS: Children prescribed antibiotic and acid suppressants in the first 2 years of life have a significant increase in future prescriptions for psychotropics, with a dose-related effect observed. This association represents a potential risk of early exposure to antibiotics and acid suppressants.

Impact of Parental Illness and Injury on Pediatric Disorders of Gut-Brain Interaction.

OBJECTIVE: To evaluate the relationship between parental injury and illness and disorders of gut-brain interaction (DGBI) in children. STUDY DESIGN: A self-controlled case series using data from the Military Health System Data Repository compared International Classification of Diseases, Ninth Revision-identified DGBI-related outpatient visits and prescriptions in 442 651 children aged 3-16 years in the 2 years before and the 2 years after the injury and/or illness of their military parent. Negative binomial regression was used to compare visit rates for constipation, fecal incontinence, abdominal pain, irritable bowel syndrome, and a composite of these before and after parental injury and/or illness. Logistic regression, clustered by child, compared the odds of stooling agent and antispasmodic prescription before and after parental injury and/or illness. RESULTS: In the 2 years following parental injury and/or illness, children had increased visits for DGBIs (adjusted incidence rate ratio [aIRR] 1.09; 95% CI 1.07-1.10), constipation (aIRR 1.07; 95% CI 1.04-1.10), abdominal pain (aIRR 1.09; 95% CI 1.07-1.12), and irritable bowel syndrome (aIRR 1.37; 95% CI 1.19-1.58). Following parental injury and/or illness, the odds of stooling agent prescription decreased (aOR 0.95; 95% CI 0.93-0.97) and the odds of antispasmodic prescription increased (aOR 1.26; 95% CI 1.18-1.36). CONCLUSIONS: Parental injury and/or illness is associated with increased healthcare use for DGBIs. Parental health should be considered by clinicians when assessing DGBIs, counseling patients, and formulating treatment plans.

Development and Assessment of a Pictographic Pediatric Constipation Action Plan.

OBJECTIVE: To assess the Uniformed Services Constipation Action Plan (USCAP) as an evidence-based, personalized, clinical action tool with pictograms to aid clinicians and families in the management of functional constipation. STUDY DESIGN: The USCAP facilitates the management functional constipation by using a health literacy-informed approach to provide instructions for pharmacotherapies and lifestyle modifications. This study included part 1 (pictogram validation) and part 2 (assessment). For part 1, pictogram transparency, translucency, and recall were assessed by parent survey (transparency ≥85%, mean translucency score ≥5, recall ≥85% required for validation). For part 2, the USCAP was assessed by parents, clinical librarians, and clinicians. Parental perceptions (n = 65) were assessed using the Consumer Information Rating Form (17 questions) to gauge comprehensibility, design quality and usefulness. Readability was assessed by 5 formulas and a Readability Composite Score was calculated. Clinical librarians (n = 3) used the Patient Education Materials Assessment Tool to measure understandability (19 questions) and actionability (7 questions) (>80% rating was acceptable). Suitability was assessed by clinicians (n = 34) using Doak's Suitability Assessment of Materials (superior ≥70% rating). RESULTS: All 12 pictograms demonstrated appropriate transparency, translucency, and recall. Parental perceptions reflected appropriate comprehensibility, design quality, and usefulness. The Readability Composite Score was consistent with a fifth-grade level. Clinical librarians reported acceptable understandability and actionability. Clinicians reported superior suitability. CONCLUSIONS: The USCAP met all criteria for clinical implementation and future study of USCAP implementation for treating children with chronic functional constipation.

Fidget Spinner Ingestions in Children-A Problem that Spun Out of Nowhere.

The Consumer Product Safety Risk Management System's injury and potential injury database records 13 cases of fidget spinner ingestion since 2016. In addition to a database query, we report 3 additional cases of fidget spinner ingestion to describe patient presentations and subsequent management strategies.

Incidence of Biliary Atresia and Timing of Hepatoportoenterostomy in the United States.

OBJECTIVE: To evaluate the incidence, trends, seasonality, and age at the time of hepatoportoenterostomy (Kasai procedure) for biliary atresia in the US. STUDY DESIGN: The triennial Health Cost and Utilization Project-Kids' Inpatient Database for 1997-2012 was used to perform a retrospective analysis of biliary atresia in the US. Infants aged <1 year of age with a diagnosis of biliary atresia who underwent a Kasai procedure were included. Nationwide infant population data were used to calculate incidence and evaluate trends. Age at the time of the Kasai procedure and the seasonality of biliary atresia were evaluated as well. RESULTS: The incidence of biliary atresia in the US was 4.47 per 100 000 and was higher in females (risk ratio [RR], 1.43; 95% CI, 1.27-1.62), Asian/Pacific Islanders (RR, 1.89; 95% CI, 1.44-2.47), and blacks (RR, 1.30; 95% CI, 1.06-1.58) compared with whites. The incidence of biliary atresia increased by an average of 7.9% per year from 1997 to 2012 (P <.001). The median age at the time of the Kasai procedure was 63 days, with no improvement over the study period (P = .64). There was no evidence of seasonality (P = .69). CONCLUSION: The incidence of biliary atresia has increased over the past 15 years, with the median age at the time of the Kasai procedure now outside the optimal window. Implementation of systematic screening measures for biliary atresia in the US are needed.

Risk Factors for Community-Associated Clostridium difficile Infection in Children.

OBJECTIVE: To characterize the medication and other exposures associated with pediatric community-associated Clostridium difficile infections (CA-CDIs). STUDY DESIGN: We performed a case-control study using billing records from the US military health system database. CA-CDI cases included children 1-18 years of age with an outpatient International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code for Clostridium difficile infection (CDI) from 2001 to 2013. Each case was matched to 3 controls without CDI by age and sex. Children hospitalized at any time before their CDI were excluded. Outpatient pharmacy records were used to identify medication exposures in the preceding 12 weeks. In addition, we evaluated recent outpatient healthcare exposure, exposure to a sibling younger than 1 year of age, or to a family member with CDI. RESULTS: A total of 1331 children with CA-CDI were identified and 3993 controls were matched successfully. Recent exposure to fluoroquinolones, clindamycin (OR 73.00; 95% CI 13.85-384.68), third-generation cephalosporins (OR 16.32; 95% CI 9.11-29.26), proton pump inhibitors (OR 8.17; 95% CI 2.35-28.38), and to multiple classes of antibiotics, each was associated strongly the subsequent diagnosis of CA-CDI. Recent exposure to outpatient healthcare clinics (OR 1.35; 95% CI 1.31-1.39) or to a family member with CDI also was associated with CA-CDI. CONCLUSIONS: CA-CDI is associated with medications regularly prescribed in pediatric practice, along with exposure to outpatient healthcare clinics and family members with CDI. Our findings provide additional support for the judicious use of these medications and for efforts to limit spread of CDI in ambulatory healthcare settings and households.

Autism Spectrum Disorders and Metabolic Complications of Obesity.

OBJECTIVES: To assess for an increased risk of obesity, type 2 diabetes mellitus, hypertension, hyperlipidemia, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis in children with autism spectrum disorders (ASD). Additionally, to determine the rates of prescribed treatment for obesity-related metabolic disorders and to determine whether treatment with psychotropic medications is associated with the development of obesity for children with ASD. STUDY DESIGN: A retrospective 1:5 case-control study was performed by use of the Military Health System database from October 2000 to September 2013. For children with ASD and matched controls, International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for obesity, type 2 diabetes mellitus, hypertension, hyperlipidemia, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, and prescriptions were obtained. Conditional logistic regression determined ORs and 95% CIs. RESULTS: A total of 48 762 individuals with ASD and 243 810 matched controls were identified. Children with ASD had significantly greater odds of having obesity (OR 1.85; 95% CI 1.78-1.92), having obesity-related disorders, and being prescribed a medication when they had these diseases. In children with ASD, mood stabilizers, antipsychotics, antiepileptic drugs, and selective serotonin reuptake inhibitors were associated with obesity. CONCLUSIONS: Children with ASD have an increased risk of obesity and obesity-related metabolic disorders. They are more likely to be prescribed medications to treat these complications, suggesting they may have more severe disease. There is a significant association between the use of some psychotropic categories and a diagnosis of obesity, suggesting that obesity in children with ASD may be partially iatrogenic.

Hospitalization for Varicella and Zoster in Children with Inflammatory Bowel Disease.

OBJECTIVE: To evaluate the association between inflammatory bowel disease (IBD) and varicella- and herpes zoster-related pediatric hospitalizations. STUDY DESIGN: We performed a cross-sectional inpatient study using the triennial Healthcare Cost and Utilization Project Kids' Inpatient Database for years 1997-2012 to evaluate the association between a secondary diagnosis of IBD and a primary diagnosis of varicella or herpes zoster for hospitalized children ages 5-20 years. Billing codes were used to identify varicella, herpes zoster, ulcerative colitis, Crohn's disease, and other immunocompromising conditions. A logistic regression model was fitted to quantify the odds of varicella or zoster between these categories. RESULTS: There were 8 828 712 weighted admissions meeting the study criteria, 4434 with varicella and 4488 with herpes zoster. There was an association of IBD and immunocompromising conditions with hospitalization for varicella and herpes zoster. This association was stronger among children with Crohn's disease (varicella OR, 12.75; 95% CI, 8.30-19.59; zoster OR, 7.91; 95% CI, 5.60-11.18) compared with children with ulcerative colitis (varicella OR 4.25; 95% CI 1.98-9.12, zoster OR 3.90; 95% CI 1.98-7.67). CONCLUSIONS: IBD in children is associated with hospitalizations for varicella and herpes zoster. These results highlight the importance of efforts to vaccinate patients with IBD without varicella immunity, ideally before the initiation of immunosuppressive therapy. Furthermore, research is needed on the safety and efficacy of the varicella vaccine in children with IBD on immunomodulators or biologic therapy.

Hypertension Prevalence, Cardiac Complications, and Antihypertensive Medication Use in Children.

OBJECTIVE: To determine the prevalence of hypertension diagnosis in children of US military members and quantify echocardiography evaluations, cardiac complications, and antihypertensive prescriptions in the post-2004 guideline era. STUDY DESIGN: Using billing data from military health insurance (TRICARE) enrollees, hypertension cases were defined as 2 or more visits with a primary or unspecified hypertension diagnosis during any calendar year or 1 such visit if with a cardiologist or nephrologist. RESULTS: During 2006-2011, the database contained an average 1.3 million subjects aged 2-18 years per year. A total of 16 322 met the definition of hypertension (2.6/1000). The incidence of hypertension increased by 17% between 2006 and 2011 (from 2.3/1000 to 2.7/1000; P < .001). Hypertension was more common in adolescents aged 12-18 years than in younger children (5.4/1000 vs 0.9/1000). Among patients with hypertension, 5585 (34%) underwent echocardiography. The frequency of annual echocardiograms increased from 22.7% to 27.7% (P < .001). In patients with echocardiography, 8.0% had left ventricular hypertrophy or dysfunction. Among the patients with hypertension, 6353 (38.9%) received an antihypertensive medication. CONCLUSION: The prevalence of hypertension in children has increased. Compliance with national guidelines is poor. Of pediatric patients with hypertension who receive an echocardiogram, 1 in 12 had identified cardiac complications, supporting the current recommendations for echocardiography in children with hypertension. Less than one-half of children with hypertension are treated with medication.

Children with Down syndrome are high-risk for severe respiratory syncytial virus disease.

OBJECTIVE: To assess Down syndrome as an independent risk factor for respiratory syncytial virus (RSV) hospitalization in children younger than 3 years of age and to evaluate illness severity. STUDY DESIGN: A retrospective cohort study of children enrolled in the military health system database was conducted. The effect of Down syndrome on RSV hospitalization was assessed by Cox proportional hazards model, while we controlled for risk factors. Disease severity was assessed by length of hospital stay, need for respiratory support, and age at hospitalization. RESULTS: The study included 633 200 children and 3 209 378 person-years. Children with Down syndrome had a hospitalization rate of 9.6% vs 2.8% in children without Down syndrome. Down syndrome had a greater adjusted hazard ratio (HR) for RSV hospitalization than most risk factors, 3.46 (95% CI 2.75-4.37). A sensitivity analysis demonstrated HR 3.21 (95% CI 2.51-4.10) for patients with Down syndrome ages 0-23 months and HR 5.07 (95% CI 2.21-11.59) ages 24-36 months. The median (IQR) length of stay of children with and without Down syndrome was 4 days (2-7) and 2 days (1-4) (P < .001). Patients with Down syndrome had a greater risk of requiring respiratory support (relative risk 5.5; 95% CI, 2.5-12.3). The median (IQR) ages at admission for children with and without Down syndrome were 9.8 months (5.5-17.7) and 3.5 months (1.7-8.7) (P < .001). CONCLUSIONS: Down syndrome is independently associated with an increased risk for RSV hospitalization. Children with Down syndrome are older at time of RSV hospitalization and have more severe RSV illness than children without Down syndrome. This increased risk for hospitalization continues beyond 24 months.

Association of Clostridium difficile infections with acid suppression medications in children.

OBJECTIVE: Multiple studies have confirmed associations between acid suppression medication and Clostridium difficile infections (CDIs) in adults. Therefore, we sought to evaluate an association between acid suppression medications and CDI in children. STUDY DESIGN: A retrospective self-controlled case series was performed utilizing billing records from the TRICARE Management Activity military health system database. Children ages 2-18 years from October 1, 2001 to July 31, 2013, who had an outpatient or inpatient record of CDI diagnosis were included. The relative incidences (RIs) of CDI or recurrent CDI were calculated comparing time periods prescribed and not prescribed proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). RESULTS: There were 2531 cases of CDI among 2437 patients, and 1190 (48.8%) were prescribed acid suppression medications. CDI were more likely to occur during periods when patients were prescribed a PPI (RI 2.36; 95% CI 2.22-2.52), H2RA (RI 1.95; 95% CI 1.63-2.34), or during periods while prescribed both simultaneously (RI 2.40; 95% CI 1.90-3.04). There were 265 (10.4%) cases that were classified as recurrent among 217 (8.9%) patients. Recurrent CDI also was found to be more likely during prescription periods of PPI (RI 1.74; 95% CI 1.51-2.00) and H2RA (RI 2.63; 95% CI 1.89-3.66). CONCLUSIONS: Acid suppression medications are associated with an increased risk of CDI and recurrent CDI. Judicious use of acid suppression medication should be considered, especially among those at highest risk for CDI.

Bacterial enteritis as a risk factor for childhood intussusception: a retrospective cohort study.

OBJECTIVE: To assess the relationship between bacterial enteritis and intussusception. STUDY DESIGN: The Patient Administration Systems and Biostatistics Activity database from January 2002 to December 2005 was examined for clinic visits or hospital admission to a Department of Defense medical facility for children age 0-5 years. The study included the International Statistical Classification of Diseases and Related Health Problems diagnosis-related group (DRG) codes for infections with Yersinia enterocolitica, Escherichia coli, Shigella species, Salmonella species, and Campylobacter. Identified patients were then assessed for the intussusception DRG code for 0-180 days postinfection. The total number of children enrolled in military treatment facilities in the same age group (denominator) was obtained. RESULTS: Bacterial enteritis significantly increased the relative risk of intussusception. An increased risk was found following infection with Salmonella, E coli, Shigella, and Campylobacter. The relative risk for intussusception following any bacterial enteritis was 40.6 (95% confidence interval = 28.6-57.5; P < .0001). CONCLUSIONS: Bacterial enteritis is a significant risk factor for the subsequent development of intussusception in children.