1
|
Hirsch S, Liu E, Nurko S, Rosen R. Ten-Year Trends in Pharmacologic Management of Gastroesophageal Reflux Disease and Pediatric Feeding Disorders in Young Children. J Pediatr 2025:114628. [PMID: 40300664 DOI: 10.1016/j.jpeds.2025.114628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 03/14/2025] [Accepted: 04/21/2025] [Indexed: 05/01/2025]
Abstract
OBJECTIVE To evaluate 10-year trends in pharmacologic management of young children with gastroesophageal reflux disease (GERD) or pediatric feeding disorder (PFD), a population at risk for over prescribing. STUDY DESIGN Single-center, retrospective cohort study of children ≤ 2 years diagnosed with GERD or PFD between January 2014 and December 2023. Prescriptions were searched for proton pump inhibitors (PPI), H2-receptor antagonists (H2RA), cyproheptadine, erythromycin, metoclopramide, or prucalopride, and procedures were searched for intrapyloric botulinum injections. The change over time in the percent of patients with GERD or PFD prescribed each medication class was assessed using the Cochran-Armatage test for trend. RESULTS 49,483 children ≤ 2 years were diagnosed with GERD or PFD, with an increasing number of patients seen annually (6516 in 2014 vs. 9109 in 2023). The percent of patients receiving any prescription for GERD or PFD declined by almost 50%, from 36.5% in 2014 to 18.7% in 2023 (P < 0.001). There was a particular decline in PPI prescriptions, with 25.3% of patients receiving PPI in 2014 and 7.1% receiving PPI in 2023 (P < 0.001), and also a decline in H2RA prescriptions, with 17.0% of patients receiving H2RA in 2014 and 11.1% receiving H2RA in 2023 (P < 0.0001). Decreases over time also were seen in the percent of patients prescribed erythromycin (P = 0.045) and metoclopramide (P = 0.006), while there was an increase in the percent of patients prescribed cyproheptadine (P = 0.009) and prucalopride (P < 0.0001). Intrapyloric botulinum injections increased but remained infrequent. CONCLUSIONS In this large, single-center study, prescriptions for young children with GERD or PFD declined over this 10-year period. There were substantial declines in PPI prescribing, contrasting with prior studies. These trends may indicate growing alignment of practice with consensus recommendations that advise against acid suppression as first-line management in this population.
Collapse
Affiliation(s)
- Suzanna Hirsch
- Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology, Hepatology & Nutrition, Boston Children's Hospital, Boston, MA.
| | - Enju Liu
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA
| | - Samuel Nurko
- Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology, Hepatology & Nutrition, Boston Children's Hospital, Boston, MA
| | - Rachel Rosen
- Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology, Hepatology & Nutrition, Boston Children's Hospital, Boston, MA
| |
Collapse
|
2
|
Hirsch S, Liu E, Rosen R. Proton Pump Inhibitors and Risk of COVID-19 Infection in Children. J Pediatr 2024; 274:114179. [PMID: 38944187 PMCID: PMC11536706 DOI: 10.1016/j.jpeds.2024.114179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/22/2024] [Accepted: 06/24/2024] [Indexed: 07/01/2024]
Abstract
OBJECTIVE To evaluate the influence of proton pump inhibitor (PPI) use on COVID-19 susceptibility and severity in children. STUDY DESIGN This retrospective, case-control study included all children ≤21 years undergoing COVID-19 polymerase chain reaction testing at a tertiary children's hospital between March 2020 and January 2023. The main exposure was PPI usage. The primary outcome was COVID-19 infection. The secondary outcome was COVID-19 hospitalization. Log-binomial regressions were used to examine associations between PPI use and these outcomes. RESULTS 116 209 patients age 8.5 ± 6.2 years underwent 234 867 COVID-19 tests. Current PPI use was associated with a decreased risk of COVID-19 test positivity compared with PPI nonuse [RR 0.85 (95% CI 0.76, 0.94), P = .002]; however, there was a significant interaction with time of testing, and an effect of PPIs was no longer seen in the final months of the study following lessening of COVID-19 precautions [RR 1.04 (95% CI 0.0.80, 1.36), P = .77]. PPI use was not associated with risk of hospitalization in patients positive for COVID-19 after adjusting for other hospitalization risk factors [RR 0.85 (95% CI 0.64, 1.13), P = .26]. CONCLUSIONS We did not find an association between PPI use and increased COVID-19 susceptibility or severity in this pediatric sample. These results provide reassuring evidence that PPIs may not worsen COVID-19 outcomes in children.
Collapse
Affiliation(s)
- Suzanna Hirsch
- Division of Gastroenterology, Hepatology & Nutrition, Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Boston Children's Hospital, Boston, MA.
| | - Enju Liu
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA
| | - Rachel Rosen
- Division of Gastroenterology, Hepatology & Nutrition, Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Boston Children's Hospital, Boston, MA
| |
Collapse
|
3
|
Chehade M, Hiremath GS, Zevit N, Oliva S, Pela T, Khodzhayev A, Jacob-Nara J, Radwan A. Disease Burden and Spectrum of Symptoms that Impact Quality of Life in Pediatric Patients with Eosinophilic Esophagitis. GASTRO HEP ADVANCES 2024; 3:1054-1068. [PMID: 39529644 PMCID: PMC11550740 DOI: 10.1016/j.gastha.2024.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 08/05/2024] [Indexed: 11/16/2024]
Abstract
Eosinophilic esophagitis (EoE) is a progressive type 2 inflammatory disease characterized by symptoms related to esophageal dysfunction and significant esophageal eosinophilic infiltration. It can affect patients from infancy through adulthood. Pediatric EoE has a multidimensional impact on the quality of life of both patients and their families. Nonspecific symptoms mimicking other gastrointestinal conditions, such as food refusal, failure to thrive, and feeding difficulties, may profoundly affect young children's eating skills, growth, and psychosocial status, as well as impact family financial conditions. In adolescence, dysphagia and esophageal food impactions often lead to feeding-related anxiety and influence social lives. Delays in diagnosis, arising from lack of awareness among families and clinicians and compensatory eating behaviors, could increase the risk of fibrostenotic complications, which may ultimately add to the symptom burden. Currently available treatment options include proton pump inhibitors, dietary therapies, swallowed topical steroids, esophageal dilation, and biologic therapy. Despite the efficacy of these approaches, disease burden may be further impacted by their limitations, including poor adherence rates, refractory disease, potential long-term safety concerns, and high costs for care. Thus, there is a need for more timely diagnosis in clinical practice and novel targeted disease-modifying therapies better tailored to treat various phenotypes of EoE, aimed at reducing the physical and psychosocial burdens on patients and their caregivers.
Collapse
Affiliation(s)
- Mirna Chehade
- Department of Pediatrics and Medicine, Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Girish S. Hiremath
- Department of Pediatrics, Monroe Carell Jr Children’s Hospital at Vanderbilt, Nashville, Tennessee
| | - Noam Zevit
- Institute of Gastroenterology, Hepatology and Nutrition, Schneider Children's Medical Center of Israel, Petach-Tikva, Israel
- Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Salvatore Oliva
- Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, Rome, Italy
| | | | | | | | - Amr Radwan
- Regeneron Pharmaceuticals Inc, Tarrytown, New York
| |
Collapse
|
4
|
Alla D, Shah DJ, Seepana M, Salian RB, Alla SSM, Krishna Mohanan M, Sabıroğlu M, Vegesna MSS, Singh A, Gupta S, Shivalingappa Rekha S. Safety of Proton Pump Inhibitors in Pediatric Population: A Systematic Review. Glob Pediatr Health 2024; 11:2333794X241248967. [PMID: 38685999 PMCID: PMC11057350 DOI: 10.1177/2333794x241248967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 03/27/2024] [Accepted: 04/05/2024] [Indexed: 05/02/2024] Open
Abstract
Objective. Commonly recommended drugs for adults and children include proton pump inhibitors (PPIs), proven effective for treating peptic diseases like stomach ulcers, GERD, and Helicobacter pylori infections in children over 1-year-old. Yet, prolonged PPI use carries higher risks of adverse reactions, prompting this study's analysis. Methods. We have performed a systematic review of 30 articles, which include a total of 762 505 pediatric patients. Results. Adverse effects were encountered in 6.98% of the population. The 5 most common adverse effects were respiratory tract complications, gastrointestinal complications, urinary tract infections, asthma, and ENT infections. Conclusion. Hence, PPIs should be prescribed only when necessary, and physicians should prioritize patient education when considering their use.
Collapse
Affiliation(s)
- Deekshitha Alla
- Andhra Medical College, Visakhapatnam, Andhra Pradesh, India
| | | | | | | | | | - Midhun Krishna Mohanan
- Sree Uthradom Thirunal (SUT) Academy of Medical Sciences, Thiruvananthapuram, Kerala, India
| | | | | | - Aradhya Singh
- Spartan Health Sciences University, Vieux Fort, Saint Lucia
| | | | | |
Collapse
|
5
|
Masarwa R, Reynier P, Lefebvre C, Platt RW, Delaney JAC, Filion KB. Prescribing trends of proton pump inhibitors and histamine blockers among children in the United Kingdom (1998-2019): A population-based assessment. Pharmacoepidemiol Drug Saf 2024; 33:e5752. [PMID: 38362652 DOI: 10.1002/pds.5752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 11/29/2023] [Accepted: 12/21/2023] [Indexed: 02/17/2024]
Abstract
PURPOSE To describe the prescribing trends of proton pump inhibitors (PPIs) and H2 receptor antagonists (H2 RAs) among children with gastroesophageal reflux in the United Kingdom between 1998 and 2019. METHODS We conducted a population-based retrospective cohort study using data from the Clinical Practice Research Datalink that included all children aged ≤18 years with a first ever diagnosis of gastroesophageal reflux between 1998 and 2019. Using negative binomial regression, we estimated crude and adjusted annual prescription rates per 1000 person-years and corresponding 95% confidence intervals (CIs) for PPIs and H2 RAs. We also assessed rate ratios of PPIs and H2 RAs prescription rates to examine changes in prescribing over time. RESULTS Our cohort included 177 477 children with a first ever diagnosis of gastroesophageal reflux during the study period. The median age was 13 years (IQR: 1, 17) among children prescribed PPIs and 0.2 years (IQR: 0.1, 0.6) among those prescribed H2 RAs. The total prescription rate of all GERD drugs was 1468 prescriptions per 1000 person-years (PYs) (95% CI 1463-1472). Overall, PPIs had a higher prescription rate (815 per 1000 PYs, 95% CI 812-818) than H2 RAs (653 per 1000 PYs 95% CI 650-655). Sex- and age-adjusted rate ratios of 2019 versus 1998 demonstrated a 10% increase and a 76% decrease in the prescription rates of PPIs and H2 RAs, respectively. CONCLUSIONS Prescription rates for PPIs increased, especially during the first half of the study period, while prescription rates for H2 RA decreased over time.
Collapse
Affiliation(s)
- Reem Masarwa
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Pauline Reynier
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Claire Lefebvre
- Department of Pediatrics, Centre Hospitalier Universitaire Ste-Justine, University of Montreal, Montreal, Quebec, Canada
| | - Robert W Platt
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
- Department of Pediatrics, McGill University, Montreal, Quebec, Canada
| | - Joseph A C Delaney
- General Internal Medicine, University of Washington, Seattle, Washington, USA
| | - Kristian B Filion
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
- Department of Medicine, McGill University, Montreal, Quebec, Canada
| |
Collapse
|
6
|
Riccio S, Marzuillo P, Santoro C. Do proton pump inhibitors reduce gastrointestinal complication when starting long-term non-steroidal anti-inflammatory drugs therapy? Arch Dis Child 2024; 109:167-169. [PMID: 37827812 DOI: 10.1136/archdischild-2023-326141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 09/23/2023] [Indexed: 10/14/2023]
Affiliation(s)
- Simona Riccio
- Department of Women's and Children's Health and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Pierluigi Marzuillo
- Department of Women's and Children's Health and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Claudia Santoro
- Department of Women's and Children's Health and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy
- Clinic of Child and Adolescent Neuropsychiatry, Departments of Physical and Mental Health, and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| |
Collapse
|
7
|
van Lennep M, Lansink F, Benninga MA, van Wijk MP. Age-dependent normal values for the 'Infant Gastroesophageal Reflux Questionnaire Revised'. Eur J Pediatr 2024; 183:445-452. [PMID: 37926716 PMCID: PMC10858078 DOI: 10.1007/s00431-023-05281-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 10/09/2023] [Accepted: 10/11/2023] [Indexed: 11/07/2023]
Abstract
The Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) is used to score and evaluate gastroesophageal reflux (GER) related symptoms such as regurgitation, irritability and crying. A cut-off of ≥ 16 has been suggested to discriminate between GER and GER-disease. However, age-specific normal values were not assessed. Aim of this study was to determine age-specific normal values in healthy infants. Cross-sectional survey in healthy infants aged 0-24 months during their regular check-ups at well-baby clinics and through an online questionnaire using the I-GERQ-R. Infants with a history of (suspected) GER-disease were excluded. Spearman's correlation coefficient was calculated to explore age-related trends. A total of 979 healthy infants (47% male, median age 6 [0-24] months) were included. Median I-GERQ-R score, regardless of age, was 6 (range: 0-27). I-GERQ-R scores significantly decreased with age (rs = -0.569, p < 0.001). Of all infants, 49 (5%) had a score of ≥ 16 which previously has been considered 'suggestive of GER-disease'. Scores of ≥ 16 were most frequently seen in newborns aged 0-4 months (16% in 0-1 months to 4% in 3-4 months) and disappeared after the age of 16 months. High scores in the first months of life were caused by a high prevalence of regurgitation, colic-associated symptoms and hiccup frequency. Conclusion: Age-dependent normal values for the I-GERQ-R show that reflux symptoms decrease in the first 24 months of life in healthy infants. Scores of ≥ 16 should not necessarily be considered abnormal in young infants. Validation as a diagnostic tool for GER-disease using age-appropriate normal values is needed. What is Known: • The Infant Gastro Esophageal Reflux Questionnaire Revised (I-GERQ-R) was developed to objectively score and evaluate GER-related symptoms in infants. • Previously a cut off of ≥ 16 has been suggested to differentiate between gastro esophageal reflux (GER) and GER-disease. What is New: • We present age-specific normal values of the I-GERQ-R in healthy infants. • I-GERQ-R scores clearly decrease with age and up to 16% of young healthy infants have a score that is above the previously suggested cut-off score of 16 for GER-disease.
Collapse
Affiliation(s)
- Marinde van Lennep
- Amsterdam UMC location University of Amsterdam, Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Meibergdreef 9, H7-292, PO Box 22700, 1100 DD, Amsterdam, The Netherlands
| | - Fréderique Lansink
- Department of General Internal Medicine, University Hospital Leuven, Leuven, Belgium
| | - Marc A Benninga
- Amsterdam UMC location University of Amsterdam, Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Meibergdreef 9, H7-292, PO Box 22700, 1100 DD, Amsterdam, The Netherlands
| | - Michiel P van Wijk
- Amsterdam UMC location University of Amsterdam, Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Meibergdreef 9, H7-292, PO Box 22700, 1100 DD, Amsterdam, The Netherlands.
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Pediatric Gastroenterology, Emma Children's Hospital, Boelelaan 1117, Amsterdam, The Netherlands.
| |
Collapse
|
8
|
Achler T, Chodick G, Shaoul R, Cohen S, Ben-Tov A, Goldshtein I. Association of early-life exposure to acid-suppressive therapy and fractures during childhood: a retrospective cohort study. Arch Dis Child 2023; 109:37-42. [PMID: 37758289 DOI: 10.1136/archdischild-2023-325802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 09/12/2023] [Indexed: 10/03/2023]
Abstract
OBJECTIVES Increased acid-suppressive therapy (AST) usage during infancy is seen worldwide, while the data on the risk for paediatric fractures associated with these drugs are scarce. We aimed to evaluate the risk for fractures associated with early-life usage of AST. METHODS This population-based retrospective propensity-matched cohort study included children born between 2005 and 2016 who used AST during the first year of life, and a 3:1 matched unexposed group. Study subjects were followed from the end of the first year of life until the earliest of the following: an outcome event (either fracture or non-fracture injury, separately), age of 10 or August 2022. The cumulative incidence of fractures and the HR of AST for fracture and non-fracture injury as negative control were calculated. RESULTS A total of 13 894 eligible AST users and 41 418 propensity score-matched non-users were included in the analysis. The cumulative incidence of fracture among children with AST (23.7%) was significantly (p<0.001) higher than non-users (21.7%) corresponding to an HR of 1.11 (95% CI 1.06 to 1.16). The HR for one to two AST purchases versus none was 1.09 (95% CI 1.04 to 1.14) and the HR for 3+ AST purchases versus none was 1.25 (95% CI 1.13 to 1.39). AST was also associated with injuries by an HR of 1.09 (95% CI 1.04 to 1.13). CONCLUSIONS AST was associated with a small but statistically significant increased incidence of fractures. We cannot exclude reporting bias or residual confounders. The clinical inference is currently unclear.
Collapse
Affiliation(s)
- Tomer Achler
- Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University Faculty of Medicine, Tel Aviv, Israel
| | - Gabriel Chodick
- Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University Faculty of Medicine, Tel Aviv, Israel
- Maccabitech Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Ron Shaoul
- Pediatric Gastroenterology and Nutrition Institute, Ruth Rappaport Children's Hospital, Rambam Medical Center, Haifa, Israel
- Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Shlomi Cohen
- Department of Pediatrics, Tel Aviv University Faculty of Medicine, Tel Aviv, Israel
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Amir Ben-Tov
- Maccabitech Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
- Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Inbal Goldshtein
- Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University Faculty of Medicine, Tel Aviv, Israel
- Maccabitech Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
| |
Collapse
|
9
|
Parmar MP, Kaleem S, Samuganathan P, Ishfaq L, Anne T, Patel Y, Bollu S, Vempati R. Impact of Proton Pump Inhibitors on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review. Cureus 2023; 15:e49883. [PMID: 38174181 PMCID: PMC10762285 DOI: 10.7759/cureus.49883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
Proton pump inhibitors (PPIs) are widely prescribed medications for the management of various gastrointestinal disorders, primarily gastroesophageal reflux disease (GERD) and peptic ulcers. However, recent concerns have emerged regarding their potential adverse effects on kidney function and their role in the progression of chronic kidney disease (CKD). This systematic review aims to comprehensively analyze the existing literature to assess the impact of PPI use on kidney function and CKD progression. We took information from PubMed, PubMed Central (PMC), and Google Scholar articles from the last 10 years, from 2013 to 2023, and looked for links between PPI use and a number of kidney-related outcomes. These included acute kidney injury, a drop in the estimated glomerular filtration rate (eGFR), and new cases of CKD. The findings of this systematic review highlight the need for a thorough evaluation of the benefits and risks associated with PPI use, particularly in patients with pre-existing kidney conditions, in order to inform clinical decision-making and improve were taken out and looked at to see if there were any links between PPI use and different kidney-related events, such as acute kidney injury, a drop in the estimated eGFR, and the development of CKD. The review also explores potential mechanisms underlying PPI-induced nephrotoxicity. The findings of this systematic review highlight the need for a thorough evaluation of the benefits and risks associated with PPI use, particularly in patients with pre-existing kidney conditions, in order to inform clinical decision-making and improve patient care. Further research is warranted to better understand the complex interplay between PPIs, kidney function, and CKD progression.
Collapse
Affiliation(s)
- Mihirkumar P Parmar
- Internal Medicine, Gujarat Medical Education and Research Society, Vadnagar, IND
| | - Safa Kaleem
- Internal Medicine, Shadan Institute of Medical Sciences, Hyderabad, IND
| | | | - Lyluma Ishfaq
- Internal Medicine, Government Medical College Srinagar, Srinagar, IND
| | - Tejawi Anne
- Internal Medicine, Gandhi Medical College & Hospital, Secunderabad, IND
| | - Yashaswi Patel
- Internal Medicine, Government Medical College Surat, Surat, IND
| | - Sashank Bollu
- Internal Medicine, Gandhi Medical College, Hyderabad, IND
| | - Roopeessh Vempati
- Internal Medicine, Gandhi Medical College & Hospital, Hyderabad, IND
- Cardiology, Heart and Vascular Institute, Detroit, USA
| |
Collapse
|
10
|
Madej J, Atanassova T, McGuire S, Cohen B, Weidner M, Zhang Y, Horton DB. Acid-suppressive medication and incidence of chronic childhood immune-mediated diseases: A scoping review. Pediatr Allergy Immunol 2023; 34:e14042. [PMID: 38010007 PMCID: PMC10683867 DOI: 10.1111/pai.14042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Use of acid-suppressive medications (ASMs), for example, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), has been rising along with the incidence of pediatric immune-mediated diseases (IMDs). We conducted a scoping review to characterize the literature about prenatal or pediatric exposure to ASMs in relation to incident pediatric IMDs. METHODS Electronic searches were conducted to identify studies from 2001 to 2023 on (a) prenatal or pediatric exposure to PPIs and/or H2RAs and (b) the risk of developing chronic IMDs during childhood. Eligible studies after title/abstract and full-text screening underwent data abstraction. RESULTS Of 26 eligible studies, 11 focused on prenatal ASM exposure and 16 on pediatric exposure. Asthma was the most commonly investigated outcome (16 studies), followed by other allergic diseases (8), eosinophilic esophagitis (3), inflammatory bowel disease (2), and other autoimmune diseases (2). Positive associations between ASM exposure and pediatric IMD outcomes emerged in all but two recent studies, which reported null or negative associations with allergic diseases. The strength of associations was similar across exposure times (prenatal/pediatric), medications (PPIs/H2RAs), and outcomes. Dose-response relationships were often present (7/11 studies). Reported effects by trimester and age of exposure varied. Commonly reported limitations were residual confounding, exposure misclassification, and outcome misclassification. CONCLUSION In summary, prenatal or pediatric exposure to PPIs and/or H2RAs has frequently, but not exclusively, been associated with the development of asthma, other allergic diseases, and chronic gastrointestinal IMDs. However, concerns remain about confounding and other sources of bias. Prescribers and families should be aware of these possible risks of ASMs.
Collapse
Affiliation(s)
- Joanna Madej
- Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
| | - Tania Atanassova
- Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
| | - Sarah McGuire
- Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
| | - Barry Cohen
- Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Melissa Weidner
- Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Yingtng Zhang
- Robert Wood Johnson Library of Health Sciences, New Brunswick, New Jersey, USA
| | - Daniel B. Horton
- Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
- Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, New Brunswick, New Jersey, USA
- Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey, USA
| |
Collapse
|
11
|
Tayal R, Yasmin S, Chauhan S, Singh TG, Saini M, Shorog E, Althubyani MM, Alsaadi BH, Aljohani F, Alenazi MA, Abutaily SA, Ansari MY. Are Proton Pump Inhibitors Contributing in Emerging New Hypertensive Population? Pharmaceuticals (Basel) 2023; 16:1387. [PMID: 37895858 PMCID: PMC10609986 DOI: 10.3390/ph16101387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/22/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
Balancing the therapeutic advantages of a medicine with its possible risks and side effects is an important part of medical practice and drug regulation. When a drug is designed to treat a particular disease or medical condition ends up causing additional risks or side effects that lead to the development of other serious health problems, it can have detrimental consequences for patients. This article explores the correlation between persistent proton pump inhibitor (PPI) use and hypertension, a common cardiovascular ailment. While PPIs are beneficial in treating various gastrointestinal problems, their availability without a prescription has resulted in self-medication and long-term use without medical monitoring. Recent findings have revealed a link between long-term PPI usage and increased cardiovascular risks, particularly hypertension. This study investigates the intricate mechanisms underlying PPI's effects, focusing on potential pathways contributing to hypertension, such as endothelial dysfunction, disruption of nitric oxide bioavailability, vitamin B deficiency, hypocalcemia, and hypomagnesemia. The discussion explains how long-term PPI use can disrupt normal endothelial function, vascular control, and mineral balance, eventually leading to hypertension. The article emphasizes the significance of using PPIs with caution and ongoing research to better understand the implications of these medications on cardiovascular health.
Collapse
Affiliation(s)
- Rohit Tayal
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (R.T.); (T.G.S.)
| | - Sabina Yasmin
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia;
| | - Samrat Chauhan
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (R.T.); (T.G.S.)
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (R.T.); (T.G.S.)
| | - Monika Saini
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala 133207, Haryana, India;
- Swami Vivekanand College of Pharmacy, Ramnagar, Banur 140601, Punjab, India
| | - Eman Shorog
- Clinical Pharmacy Department, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia;
| | - Maryam M. Althubyani
- Department of Clinical Services, Pharmaceutical Care Services, King Salman Medical City, Ministry of Health MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia; (M.M.A.); (B.H.A.)
| | - Baiaan H. Alsaadi
- Department of Clinical Services, Pharmaceutical Care Services, King Salman Medical City, Ministry of Health MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia; (M.M.A.); (B.H.A.)
| | - Fatimah Aljohani
- Prince Sultan Armed Forces Hospital, Al Madenah Al Monwarah 42375, Saudi Arabia;
| | - Maram A. Alenazi
- Pharmaceutical Care Services, King Salman Specialist Hospital, Ministry of Health (MOH), Hail 55471, Saudi Arabia;
| | - Sarah A. Abutaily
- Ambulatory Care Clinical, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia;
| | - Mohammad Yousuf Ansari
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala 133207, Haryana, India;
| |
Collapse
|
12
|
Alosaily YA, Alfallaj JM, Alabduljabbar JS, Alfehaid EF, Alfayez OM, Elrasheed M. Appropriateness of proton pump inhibitors use in noncritically ill hospitalized children in a tertiary hospital in Saudi Arabia. Saudi Pharm J 2023; 31:101723. [PMID: 37608963 PMCID: PMC10440568 DOI: 10.1016/j.jsps.2023.101723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/24/2023] [Indexed: 08/24/2023] Open
Abstract
Background Studies assessing the appropriate use of proton pump inhibitors (PPIs) for hospitalized noncritically ill pediatric patients are lacking. Therefore, this study aimed to assess the suitability of PPI prescriptions in noncritically ill pediatric patients. Methods This cross sectional retrospective study was conducted at a maternity hospital in Qassim, Saudi Arabia from November 2020 to January 2021. All noncritically ill hospitalized children aged 14 years and below who received PPIs were included. The endpoints included the number and percentage of patients who appropriately received PPIs in general and in each age category. The collected data were analyzed using Microsoft Excel (version 2208, Microsoft Corp., Redmond, WA, USA). Results In total, 332 medical records were screened, of which 246 were included. Of all patients, 49.2% were children and 50.8% were infants, with the average age at admission being 5.39 ± 5.4 years years. More than half of the patients were female, and the average weight of patients was 19.8 kg. Omeprazole was appropriately used in 95 (38.5%) patients. Based on age groups, omeprazole was appropriately used in 66.3% of children and 38.4% of infants. Conclusion The use of omeprazole in noncritically ill pediatrics was only deemed appropriate in 38.6% of the study population. This result indicates that this medication was overused in the institution. Additional research is required to confirm this on a nationwide scale.
Collapse
Affiliation(s)
- Yousif A. Alosaily
- Pharmacy Department, Maternity and Children Hospital Buraydah, Qassim, Saudi Arabia
| | | | | | | | - Osamah M. Alfayez
- Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia
| | | |
Collapse
|
13
|
Saniasiaya J, Kulasegarah J. The link between airway reflux and non-acid reflux in children: a review. Braz J Otorhinolaryngol 2023; 89:329-338. [PMID: 35659765 PMCID: PMC10071540 DOI: 10.1016/j.bjorl.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/26/2022] [Accepted: 05/06/2022] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE Airway reflux, a member of extra-esophageal reflux, has been linked to countless respiratory pathologies amongst children. The advent of novel instrumentation has enabled the discovery of non-acid reflux which was postulated as the main culprit of airway reflux. The objective of this review is to outline the association between non-acid reflux and airway reflux in children. METHODS A comprehensive review of recent literature on non-acid reflux and airway reflux in children was conducted. Studies ranged from January 2010 till November 2021 were searched over a period of a month: December 2021. RESULTS A total of eleven studies were identified. All studies included in this review revealed a strong link between non-acid reflux and airway reflux in children. 6 of the included studies are prospective studies, 3 retrospective studies, 1 cross-section study, and type of study was not mentioned in 1 study. The most common reported respiratory manifestation of non-acid reflux in children was chronic cough (7 studies). Predominant non-acid reflux was noted in 4 studies. The total number of children in each study ranges from 21 to 150 patients. MII-pH study was carried out in all studies included as a diagnostic tool for reflux investigation. CONCLUSION Non-acid reflux is the culprit behind airway reflux as well as other myriads of extra-esophageal manifestations in children. Multicentre international studies with a standardized protocol could improve scientific knowledge in managing non-acid reflux in airway reflux amongst children.
Collapse
Affiliation(s)
- Jeyasakthy Saniasiaya
- University of Malaya, Faculty of Medicine, Department of Otorhinolaryngology, Wilayah Persekutuan Kuala Lumpur, Malaysia.
| | - Jeyanthi Kulasegarah
- University of Malaya, Faculty of Medicine, Department of Otorhinolaryngology, Wilayah Persekutuan Kuala Lumpur, Malaysia
| |
Collapse
|
14
|
Acid Suppression and Antibiotics Administered during Infancy Are Associated with Celiac Disease. J Pediatr 2023; 254:61-67.e1. [PMID: 36265574 DOI: 10.1016/j.jpeds.2022.10.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 10/08/2022] [Accepted: 10/12/2022] [Indexed: 11/29/2022]
Abstract
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.
Collapse
|
15
|
La prise en charge médicale du reflux gastro-œsophagien chez les nourrissons en santé. Paediatr Child Health 2022. [PMCID: PMC9792279 DOI: 10.1093/pch/pxac069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Abstract
Les symptômes cliniques attribués au reflux gastro-œsophagien pathologique chez les nourrissons nés à terme et en santé sont non spécifiques et rappellent des comportements adaptés à l’âge. Le présent point de pratique analyse les données probantes sur la prise en charge médicale recommandée de cette affection courante. Les recommandations à jour en vue de la prise en charge de ce type de reflux comprennent les modifications à l’alimentation, telles que l’épaississement des aliments ou l’évitement des protéines du lait de vache. Les données probantes à l’égard d’une prise en charge pharmacologique, y compris les traitements antiacides ou les agents procinétiques, sont limitées et démontrent que leurs risques sont souvent supérieurs à leurs éventuels avantages en raison des importantes préoccupations liées à l’innocuité et aux effets secondaires. Les traitements antiacides ne doivent pas être utilisés systématiquement chez les nourrissons présentant un reflux gastro-œsophagien pathologique. Ils sont plus susceptibles d’être utiles pour soigner des symptômes évocateurs d’une œsophagite érosive. Les données probantes sur la prise en charge des symptômes attribués à ce type de reflux chez les nourrissons de moins d’un an qui sont nés à terme et sont autrement en santé sont exposées, et la surprescription de médicaments est déconseillée dans cette population. Les conseils préventifs sur la résolution naturelle des symptômes de reflux sont recommandés.
Collapse
|
16
|
Brusselaers N, Pereira M, Alm J, Engstrand L, Engstrand Lilja H. Effect of proton pump inhibitors in infants with esophageal atresia on the gut microbiome: a pilot cohort. Gut Pathog 2022; 14:47. [PMID: 36527125 PMCID: PMC9758939 DOI: 10.1186/s13099-022-00518-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 11/08/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND The effects of proton-pump inhibitors (PPIs) on the infant microbiome remain unclear. Swedish pilot cohort study to assess the longitudinal effect of long-term PPI on the infant gut microbiome, including ten newborn infants operated for esophageal atresia exposed to PPIs (mean 57 weeks), compared to healthy one-year-old controls. All children were born vaginally and were otherwise healthy. Within- and between sample diversity of the fecal microbiome was assessed using untargeted whole genome Shotgun metagenomics which sequences all the DNA in the sample and can capture genes rather than a taxonomic fingerprint. RESULTS A longer duration of PPI-use was associated with considerable changes in evenness and high variation on diversity within samples compared to a shorter duration of use. The limited difference between baseline samples and controls suggests that this shift was most likely due to the drug exposure and not the underlying alterations on the microbiome. We found no associations with the number of antibiotic treatment episodes among the PPI-users. CONCLUSION Prolonged PPI-use may alter the early infant gut microbiome composition, especially those with the most prolonged duration of use.
Collapse
Affiliation(s)
- Nele Brusselaers
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, 17165 Stockholm, Sweden
- Global Health Institute, University of Antwerp, B-2610 Antwerp, Belgium
- Department of Head and Skin, Ghent University, B-9000 Ghent, Belgium
| | - Marcela Pereira
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, 17165 Stockholm, Sweden
| | - Johan Alm
- Department of Clinical Science, Karolinska Institutet, 17165 Stockholm, Sweden
- Sachs’ Children and Youth Hospital, Södersjukhuset, 11883 Stockholm, Sweden
| | - Lars Engstrand
- Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solnavägen 9, 17165 Stockholm, Sweden
| | - Helene Engstrand Lilja
- Department of Women’s and Children’s Health, Karolinska Institutet, 17165 Stockholm, Sweden
| |
Collapse
|
17
|
Chevalier I, Beck CE, Doré-Bergeron MJ, Orkin J. Medical management of gastro-esophageal reflux in healthy infants. Paediatr Child Health 2022; 27:503-511. [PMID: 36583075 PMCID: PMC9792283 DOI: 10.1093/pch/pxac068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 02/17/2022] [Indexed: 12/28/2022] Open
Abstract
Clinical symptoms attributed to gastro-esophageal reflux disease (GERD) in healthy term infants are non-specific and overlap with age-appropriate behaviours. This practice point reviews the evidence for medically recommended management of this common condition. Current recommendations to manage GERD include feeding modifications such as thickening feeds or avoiding cow's milk protein. There is limited evidence for pharmacological management, including acid suppressive therapy or prokinetic agents, with the risks of such treatments often outweighing possible benefits due to significant safety and side effect concerns. Acid-suppressive therapy should not be routinely used for infants with GERD and is most likely to be useful in the context of symptoms that suggest erosive esophagitis. Evidence for managing symptoms attributed to GERD in otherwise healthy term infants less than 1 year of age is presented, and the over-prescription of medications in this population is discouraged. Anticipatory guidance regarding the natural resolution of reflux symptoms is recommended.
Collapse
Affiliation(s)
- Isabelle Chevalier
- Canadian Paediatric Society, Acute Care Committee, Community Paediatrics Committee, Ottawa, Ontario, Canada
| | - Carolyn E Beck
- Canadian Paediatric Society, Acute Care Committee, Community Paediatrics Committee, Ottawa, Ontario, Canada
| | - Marie-Joëlle Doré-Bergeron
- Canadian Paediatric Society, Acute Care Committee, Community Paediatrics Committee, Ottawa, Ontario, Canada
| | - Julia Orkin
- Canadian Paediatric Society, Acute Care Committee, Community Paediatrics Committee, Ottawa, Ontario, Canada
| |
Collapse
|
18
|
Lyamouri M, Mårild K, Gaardskaer Nielsen R, Størdal K. Proton pump inhibitors for infants in three Scandinavian countries increased from 2007-2020 despite international recommendations. Acta Paediatr 2022; 111:2222-2228. [PMID: 35860963 DOI: 10.1111/apa.16491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 07/08/2022] [Accepted: 07/19/2022] [Indexed: 11/28/2022]
Abstract
AIM There is weak evidence that proton pump inhibitors (PPIs) alleviate non-specific complaints often attributed to gastroesophageal reflux in infancy and international guidelines do not recommend their use. We studied PPIs dispensed for infants in three Nordic countries. METHODS This was an observational population-based study of infants living in Norway, Sweden and Denmark in 2007-2020. We used nationwide pharmaceutical registers to study dispensed PPIs. The data provided a total of 3.3 million observed years on about 240,000 annual births. RESULTS The overall use of PPIs in infancy showed a marked increase in all three countries from 2007-2020. In 2020, PPI dispensing was 46.4, 23.4 and 18.9 per 1000 per year in infants aged 0-11 months in Denmark, Norway and Sweden. These were increases of 357%, 585% and 556% respectively. Although the rate was highest in Denmark, it had decreased by 42% in the last three years of the study. CONCLUSION Despite international recommendations against routine PPI prescribing in infancy, dispensed PPIs increased more than four-fold on average in three Nordic countries from 2007-2020. The reason for this notable increase could not be established from the data, but the large variations over time, and between the countries, probably indicated unwarranted use.
Collapse
Affiliation(s)
| | - Karl Mårild
- Department of pediatrics, Sahlgrenska academy, Gothenburg University, Gothenburg, Sweden; Department of pediatric gastroenterology, Queen Silvia Children's hospital, Gothenburg, Sweden
| | | | - Ketil Størdal
- Department of pediatric research, University of Oslo, Oslo, Norway.,Division of pediatric and adolescent medicine, Oslo University Hospital, Oslo, Norway
| |
Collapse
|
19
|
Yang S, Trinh NTH, Chalumeau M, Kaguelidou F, Ruemmele FM, Milic D, Lemaitre M, Cohen JF, Taine M. Pediatric Prescriptions of Proton Pump Inhibitors in France (2009-2019): A Time-Series Analysis of Trends and Practice Guidelines Impact. J Pediatr 2022; 245:158-164.e4. [PMID: 35120983 DOI: 10.1016/j.jpeds.2022.01.041] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/28/2021] [Accepted: 01/25/2022] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To describe the ambulatory proton pump inhibitor (PPI) prescription in French children, its trends, and the impact of French (2014) and international (2018) clinical guidelines. STUDY DESIGN We described PPI prescription rates based on national dispensation data in French children (IQVIA's Xponent database, 2009-2019). Using a segmented linear regression, we assessed the impact of clinical guidelines on PPI prescription rates. Analyses were performed for the overall pediatric population and by age subgroups (infants <2 years old, children 2-11 years old, adolescents 12-17 years old). RESULTS During the study period, 8 060 288 pediatric PPI prescriptions were filled, with a mean PPI prescription rate of 52.5 per 1000 inhabitants per year. Between 2009 and 2019, the PPI prescription rate increased by 41% in the overall pediatric population (+110% in infants). The PPI prescription rate showed seasonal patterns with peaks in winter. After the release of French guidelines, significant decreases in trends of prescription rates occurred overall (change in trend -0.28, 95% CI -0.34;-0.23) and across all age groups. In infants, this change in trend was not sufficient to reverse the PPI prescription rate that was still increasing over time. In children, the PPI prescription rate slightly decreased and in adolescents, it was stable. After the release of international guidelines, a significant decrease in trend occurred in adolescents only (change in trend -0.26, 95% CI -0.47; -0.04). CONCLUSIONS The pediatric PPI prescription rate in France was high, displayed a major increase over the last decade, mainly among infants, and was modestly affected by clinical guidelines.
Collapse
Affiliation(s)
- Shuai Yang
- Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Centre for Epidemiology and Statistics (CRESS), Université de Paris, Paris, France
| | - Nhung T H Trinh
- Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Centre for Epidemiology and Statistics (CRESS), Université de Paris, Paris, France; IQVIA, La Défense, France
| | - Martin Chalumeau
- Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Centre for Epidemiology and Statistics (CRESS), Université de Paris, Paris, France; Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants malades Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France.
| | - Florentia Kaguelidou
- Department of Pediatric Pharmacology and Pharmacogenetics, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France; Inserm, Clinical Investigation Center, Paris, France
| | - Frank M Ruemmele
- Pediatric Gastroenterology Hepatology and Nutrition, Necker-Enfants malades Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France; Institut Imagine, Inserm U 1163, Paris, France
| | | | | | - Jérémie F Cohen
- Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Centre for Epidemiology and Statistics (CRESS), Université de Paris, Paris, France; Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants malades Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France
| | - Marion Taine
- Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Centre for Epidemiology and Statistics (CRESS), Université de Paris, Paris, France
| |
Collapse
|
20
|
Harris J, Chorath K, Balar E, Xu K, Naik A, Moreira A, Rajasekaran K. Clinical Practice Guidelines on Pediatric Gastroesophageal Reflux Disease: A Systematic Quality Appraisal of International Guidelines. Pediatr Gastroenterol Hepatol Nutr 2022; 25:109-120. [PMID: 35360381 PMCID: PMC8958056 DOI: 10.5223/pghn.2022.25.2.109] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 10/28/2021] [Accepted: 02/06/2022] [Indexed: 12/18/2022] Open
Abstract
PURPOSE While regurgitation is a common and often benign phenomenon in infants and younger children, it can also be a presenting symptom of gastroesophageal reflux disease (GERD). If untreated, GERD can lead to dangerous or lifelong complications. Clinical practice guidelines (CPGs) have been published to inform clinical diagnosis and management of pediatric GERD, but to date there has been no comprehensive review of guideline quality or methodological rigor. METHODS A systematic literature search was performed, and a total of eight CPGs pertaining to pediatric GERD were identified. These CPGs were evaluated using the Appraisal of Guidelines for Research and Evaluation instrument. RESULTS Three CPGs were found to be "high" quality, with 5 of 6 domains scoring >60%, one "average" quality, with 4 of 6 domains meeting that threshold, and the remaining four "low" quality. CONCLUSION Areas of strength among the CPGs included "Scope and Purpose" and "Clarity and Presentation," as they tended to be well-written and easily understood. Areas in need of improvement were "Stakeholder Involvement," "Rigor of Development," and "Applicability," suggesting these CPGs may not be appropriate for all patients or providers. This analysis found that while strong CPGs pertaining to the diagnosis and treatment of pediatric GERD exist, many published guidelines lack methodological rigor and broad applicability.
Collapse
Affiliation(s)
- Jacob Harris
- Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, USA
| | - Kevin Chorath
- Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, USA
| | - Eesha Balar
- Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, USA
| | - Katherine Xu
- Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, USA
| | - Anusha Naik
- Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, USA
| | - Alvaro Moreira
- Department of Pediatrics, University of Texas Health-San Antonio, San Antonio, TX, USA
| | - Karthik Rajasekaran
- Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, USA.,Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA
| |
Collapse
|
21
|
Dipasquale V, Cicala G, Spina E, Romano C. A Narrative Review on Efficacy and Safety of Proton Pump Inhibitors in Children. Front Pharmacol 2022; 13:839972. [PMID: 35222047 PMCID: PMC8866943 DOI: 10.3389/fphar.2022.839972] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/20/2022] [Indexed: 12/21/2022] Open
Abstract
Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and include omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole. Their use in pediatrics is approved for children older than 1 year, for the short-term treatment of symptomatic gastroesophageal reflux disease (GERD), healing of erosive esophagitis, treatment of peptic ulcer disease, and eradication of Helicobacter pylori. PPIs are also considered the standard of care for pediatric eosinophilic esophagitis. Despite the strict range of indications, the use of this class of molecules has increased in all pediatric age ranges. The long-term gastric acid suppression in children has been linked to increased risks of gastrointestinal and lower respiratory tract infections, bone fractures, and allergy. This study aims to provide a comprehensive overview of the mechanism of actions, use (and misuse) in infants and children, and safety of PPIs.
Collapse
Affiliation(s)
- Valeria Dipasquale
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy
| | - Giuseppe Cicala
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Edoardo Spina
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy
| |
Collapse
|
22
|
Hines M, Hardy N, Martens A, Zimmerman E. Birth Order Effects on Breastfeeding Self-Efficacy, Parent Report of Problematic Feeding and Infant Feeding Abilities. JOURNAL OF NEONATAL NURSING : JNN 2022; 28:16-20. [PMID: 35095321 PMCID: PMC8797021 DOI: 10.1016/j.jnn.2021.07.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The goal of this prospective study was to identify effects of birth order on breastfeeding self-efficacy, parental-report of infant feeding behaviors, infant non-nutritive sucking and oral feeding skills in full-term infants at 3-months. Mothers were separated into primipara and multipara groups, and infants were grouped into siblings and no siblings groups. Parents completed the Breastfeeding Self-Efficacy Scale-Short Form, and Neonatal Eating Assessment Tool-Breastfeeding and Bottle-feeding scales. Non-nutritive sucking was assessed using a custom research pacifier and researchers completed the Oral Feeding Skills scale to assess feeding performance. Fifty-six mother-infant dyads (55% male) were included. Primipara mothers reported significantly lower breastfeeding self-efficacy and more feeding problems across breast and bottle-feeds on the Neonatal Eating Assessment Tool. There were no significant differences in non-nutritive sucking or oral feeding skills between infant groups. First-time mothers require more infant feeding support as they exhibited lower breastfeeding self-efficacy and reported more problematic feeding behaviors.
Collapse
|
23
|
Franciosi JP, Mougey EB, Dellon ES, Gutierrez-Junquera C, Fernandez-Fernandez S, Venkatesh RD, Gupta SK. Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions. J Asthma Allergy 2022; 15:281-302. [PMID: 35250281 PMCID: PMC8892718 DOI: 10.2147/jaa.s274524] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 01/14/2022] [Indexed: 12/11/2022] Open
Abstract
Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE.
Collapse
Affiliation(s)
- James P Franciosi
- Division of Gastroenterology, Nemours Children’s Hospital, Orlando, FL, USA
- College of Medicine, University of Central Florida, Orlando, FL, USA
- Correspondence: James P Franciosi, Division of Gastroenterology, Nemours Children’s Hospital, 6535 Nemours Parkway, Orlando, FL, 32827, USA, Email
| | - Edward B Mougey
- Center for Pharmacogenomics and Translational Research, Nemours Children’s Health System, Jacksonville, FL, USA
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Carolina Gutierrez-Junquera
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Autonomous University of Madrid, Madrid, Spain
| | | | - Rajitha D Venkatesh
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children’s Hospital, Columbus, OH, USA
| | - Sandeep K Gupta
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine and Community Health Network, Indianapolis, IN, USA
| |
Collapse
|
24
|
Tang Girdwood SC, Rossow KM, Van Driest SL, Ramsey LB. Perspectives from the Society for Pediatric Research: pharmacogenetics for pediatricians. Pediatr Res 2022; 91:529-538. [PMID: 33824446 PMCID: PMC8492778 DOI: 10.1038/s41390-021-01499-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 03/12/2021] [Indexed: 12/26/2022]
Abstract
This review evaluates the pediatric evidence for pharmacogenetic associations for drugs that are commonly prescribed by or encountered by pediatric clinicians across multiple subspecialties, organized from most to least pediatric evidence. We begin with the pharmacogenetic research that led to the warning of increased risk of death in certain pediatric populations ("ultrarapid metabolizers") who are prescribed codeine after tonsillectomy or adenoidectomy. We review the evidence for genetic testing for thiopurine metabolism, which has become routine in multiple pediatric subspecialties. We discuss the pharmacogenetic research in proton pump inhibitors, for which clinical guidelines have recently been made available. With an increase in the prevalence of behavioral health disorders including attention deficit hyperactivity disorder (ADHD), we review the pharmacogenetic literature on selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, and ADHD medications. We will conclude this section on the current pharmacogenetic data on ondansetron. We also provide our perspective on how to integrate the current research on pharmacogenetics into clinical care and what further research is needed. We discuss how institutions are managing pharmacogenetic test results and implementing them clinically, and how the electronic health record can be leveraged to ensure testing results are available and taken into consideration when prescribing medications. IMPACT: While many reviews of pharmacogenetics literature are available, there are few focused on pediatrics. Pediatricians across subspecialties will become more comfortable with pharmacogenetics terminology, know resources they can use to help inform their prescribing habits for drugs with known pharmacogenetic associations, and understand the limitations of testing and where further research is needed.
Collapse
Affiliation(s)
- Sonya C Tang Girdwood
- Division of Hospital Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Division of Clinical Pharmacology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
| | - Katelyn M Rossow
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sara L Van Driest
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Laura B Ramsey
- Division of Clinical Pharmacology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| |
Collapse
|
25
|
Does feeding modification strategies help improve reflux symptoms in NICU infants? J Perinatol 2022; 42:286-288. [PMID: 35031689 DOI: 10.1038/s41372-021-01289-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/05/2021] [Accepted: 11/29/2021] [Indexed: 11/08/2022]
|
26
|
Kollins F, Supriatmo S, Saragih R, Ilhamd I. Effectivity of Esomeprazole Compared with Lansoprazole in the Treatment of Pediatric with Gastritis. Open Access Maced J Med Sci 2021. [DOI: 10.3889/oamjms.2021.7191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: The administration of proton pump inhibitor (PPI) therapy in pediatric patients has also increased dramatically during the last three decades. Clinical trials comparison of esomeprazole and lansoprazole for pediatric were limited.
AIM: This study focused on comparing the effectivity of Esomeprazole with lansoprazole for healing gastritis symptoms in pediatric patients.
METHODS: A randomized and single blind (assessors) controlled clinical trial was done at H. Adam Malik hospital at Medan. Patients that complied with study’s criteria and signed informed consent were collected information about the symptoms. Confirmation diagnosis of g astritis by gastroscopy, then randomized into lansoprazole treatment group (15 mg if < 30 kg and 30 mg if > 30 kg) or esomeprazole treatment group (0,4–0,8 mg per Kg body weight). Medication for both groups will be given orally for 14 day s, then evaluated for the initial symptoms. p -value of this study was calculated with the χ2 test.
RESULTS: Fifty two patients confirmed gastritis were enrolled in this study; 27 patients received lansoprazole and 25 patients received esomeprazole. There was no difference of effectivity between the two groups for vomiting, hematemesis, and nausea. Lansoprazole treatment for 14 days has a significant difference for abdominal pain recovery from esomeprazole treatment. The lansoprazole groups have 92% free of abdominal pain compared to the esomeprazole group for only 66% free of abdominal pain.
CONCLUSION: There was no significant difference between lansoprazole and esomeprazole therapy.
Collapse
|
27
|
Dipasquale V, Cicala G, Laganà F, Cutroneo P, Felicetti P, Potenza S, Trimarchi G, Spina E, Romano C. Adverse reactions related to proton pump inhibitors in pediatric population: an analysis of spontaneous reporting data. Expert Opin Drug Saf 2021; 21:127-132. [PMID: 34494498 DOI: 10.1080/14740338.2021.1978975] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The use of proton pump inhibitors (PPIs) has increased in the last 10 years in children. Data regarding their safety profile are limited. The aim of this study was to analyze data from the Italian spontaneous reporting system (SRS) database to evaluate the incidence and characteristics of PPI-related adverse drug reactions (ADRs) in children. RESEARCH DESIGN AND METHODS This was an observational, retrospective study analyzing PPI-related ADR reports in children in the Italian SRS database between January 1st, 2001, and December 31st, 2020. ADRs were coded according to the system organ class term level. Factors associated with ADR seriousness were investigated. RESULTS Seventy spontaneous reports of ADRs related to PPIs were analyzed. Esomeprazole and lansoprazole caused the highest number of ADRs equally (27% respectively), and the most frequently reported ADRs presented with gastrointestinal (24%) and/or skin manifestations (21.3%). More than a half of PPI prescriptions were off label for pediatric population. Serious ADRs were 19 (27.1%). Serious ADRs were more frequent in reports presenting PPIs combined with other drugs in comparison to reports with PPI single therapies (p = 0.03). CONCLUSIONS PPI-related ADRs in children are mostly not serious, and combination therapy seems to be associated with ADR seriousness.
Collapse
Affiliation(s)
- Valeria Dipasquale
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy
| | - Giuseppe Cicala
- Sicilian Regional Pharmacovigilance Center, University Hospital of Messina, Messina, Italy
| | - Francesca Laganà
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy
| | - Paola Cutroneo
- Sicilian Regional Pharmacovigilance Center, University Hospital of Messina, Messina, Italy
| | | | | | | | - Edoardo Spina
- Sicilian Regional Pharmacovigilance Center, University Hospital of Messina, Messina, Italy
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi," University of Messina, Messina, Italy
| |
Collapse
|
28
|
Fisher J, McLaughlin F, Fawkes N, Tipple H, Coyle C, Dettmar PW. A Novel In Vitro Model for Determining the Optimum pH and Dose Volume of New Liquid Alginate for Infant Reflux Suppression. Drugs R D 2021; 21:331-339. [PMID: 34283413 PMCID: PMC8363677 DOI: 10.1007/s40268-021-00356-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2021] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND Gastroesophageal reflux frequently occurs in infants from birth to 2 years and is characterised by reflux and regurgitation often occurring during or immediately after feeds. These reflux events can range in both frequency and severity, and as the reflux events increase, they become increasingly distressing for both the infant and the parent. The study aimed to characterise the properties of a new infant liquid alginate product, determining the optimum gastric pH and dose volume for maximum reflux suppressant activity. METHODS An in vitro infant stomach model was designed and developed that allowed products to be assessed for their reflux suppression activity. The validation of the model was completed by three independent operators comparing a milk control with infant Gaviscon to evaluate the models' robustness, reproducibility, and ease of use. The model was used to establish reflux suppression activity of a new liquid alginate infant formulation in comparison with a milk control. Suppression activity was assessed at varying doses and pH within a physiological range. RESULTS The validation study demonstrated no significant difference in refluxate volumes for the milk control within each reflux event when comparing across the three individual operators. Similarly, no statistical differences were seen during the infant Gaviscon experiments, confirming the robustness and reproducibility of the model. Significant reflux suppression was seen across the pH range (except at pH 5.75); the pH most advantageous for reflux suppression was pH 5.25. The optimum dose volume for consistently suppressing reflux was shown to be 5 ml. An infant stomach model was designed for evaluating reflux suppression activity of a formulation of liquid alginate. The optimum gastric pH and dose volume for demonstrating significant reflux suppression and the thickening of formula milk by the infant liquid alginate formulation were established. CONCLUSION This study confirms the mode of action of the alginate formula, demonstrating a superior reduction in the retrograde movement of in vitro gastric contents and volume of regurgitation. The study also demonstrates that optimal performance occurs in conditions that are in line physiologically with the target patient. Both actions compliment and support the efficacy of the alginate formulation as a reflux therapy agent.
Collapse
Affiliation(s)
- Jeanine Fisher
- Technostics Limited, Castle Hill Hospital, Daisy Building, Castle Road, Cottingham, HU16 5JQ, East Yorkshire, UK
| | | | - Neil Fawkes
- Reckitt, Digestive Relief, Dansom Lane, Hull, HU8 7DS, UK
| | - Hannah Tipple
- Reckitt, Digestive Relief, Dansom Lane, Hull, HU8 7DS, UK
| | - Cathal Coyle
- Reckitt, Digestive Relief, Dansom Lane, Hull, HU8 7DS, UK
| | - Peter W Dettmar
- Technostics Limited, Castle Hill Hospital, Daisy Building, Castle Road, Cottingham, HU16 5JQ, East Yorkshire, UK.
| |
Collapse
|
29
|
Junko F, Moore D, Omari T, Seiboth G, Abu-Assi R, Hammond P, Couper R. Multichannel impedance monitoring for distinguishing nonerosive reflux esophagitis with minor changes on endoscopy in children. Ther Adv Gastrointest Endosc 2021; 14:26317745211030466. [PMID: 34350397 PMCID: PMC8287343 DOI: 10.1177/26317745211030466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/15/2021] [Indexed: 12/05/2022] Open
Abstract
Objectives: There are reports describing the relationship between baseline impedance
level and esophageal mucosal integrity at endoscopy, such as erosive and
nonerosive reflux esophagitis. However, many children with symptoms of
gastroesophageal reflux disease have normal findings or minor changes on
esophagogastroduodenoscopy. We aimed to examine whether modest changes at
esophagogastroduodenoscopy can be evaluated and correlated with esophageal
multichannel intraluminal impedance monitoring. Methods: Patients (ages 0–17 years) with upper gastrointestinal symptoms who underwent
combined esophagogastroduodenoscopy and multichannel intraluminal impedance
monitoring at the Women’s and Children’s Hospital, Adelaide, Australia,
between 2014 and 2016 were retrospectively studied and the following data
were collected and used for analysis: demographics, multichannel
intraluminal impedance data, included baseline impedance. Endoscopic
findings were classified by modified Los Angeles grading, Los Angeles
N as normal, Los Angeles M as with minimal change such
as the erythema, pale mucosa, or friability of the mucosa following biopsy.
Patients on proton pump inhibitor were excluded. Results: Seventy patients (43 boys; 61%) were enrolled with a mean age of 7.9 years
(range 10 months to 17 years). Fifty-one patients (72.9%) were allocated to
Los Angeles N, while Los Angeles M was
evident in 19 patients (27.1%). Statistically significant differences were
observed in the following parameters: frequency of acid and nonacid reflux
and baseline impedance in channels 5 and 6. The median values of the data
were 18.3 episodes, 16.0 episodes, 2461.0 Ω, 2446.0 Ω in Los Angeles
N, 36.0 episodes, 31.0 episodes, 2033.0 Ω, 2009.0 Ω in
Los Angeles M, respectively. Conclusion: Lower baseline impedance is helpful in predicting minimal endoscopic changes
in the lower esophagus. A higher frequency of acid and nonacid reflux
episodes was also predictive of minimal endoscopic change in the lower
esophagus.
Collapse
Affiliation(s)
- Fujino Junko
- Saitama Medical Center, Dokkyo Medical University, 2-1-50 Minamikoshigaya, Koshigaya-shi, Saitama 343-8555, Japan
| | - David Moore
- Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, SA, Australia
| | - Taher Omari
- School of Medicine, Flinders University, Adelaide, SA, Australia
| | - Grace Seiboth
- Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, SA, Australia
| | - Rammy Abu-Assi
- Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, SA, Australia
| | - Paul Hammond
- Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, SA, Australia
| | - Richard Couper
- Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, SA, Australia
| |
Collapse
|
30
|
Orel R, Benninga MA, Broekaert IJ, Gottrand F, Papadopoulou A, Ribes-Koninckx C, Thomson M, Wilschanski M, Thapar N. Drugs in Focus: Proton Pump Inhibitors. J Pediatr Gastroenterol Nutr 2021; 72:645-653. [PMID: 33847286 DOI: 10.1097/mpg.0000000000003063] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Proton pump inhibitors (PPIs) are amongst the most commonly prescribed drugs in infants and children with the last decades witnessing a dramatic rise in their utilization. Although PPIs are clearly effective when used appropriately and have been regarded as safe drugs, there is growing evidence regarding their potential adverse effects. Although, largely based on adult data it is clear that many of these are also relevant to pediatrics. PPI use potentially affects gastrointestinal microbiota composition and function, decreases defence against pathogens resulting in increased risk for infections, interferes with absorption of minerals and vitamins leading to specific deficiencies and increased risk for bone fractures as well as interferes with protein digestion resulting in increased risk of sensitization to allergens and development of allergic diseases and eosinophilic esophagitis. An association with gastric, liver and pancreatic cancer has also been inferred from adult data but is tenuous and causation is not proven. Overall, evidence for these adverse events is patchy and not always compelling. Overall, the use of PPIs, for selected indications with a good evidence base, has significant potential benefit but carries more caution in infants and children. Pediatricians should be aware of the concerns regarding the potential adverse events associated with their use.
Collapse
Affiliation(s)
- Rok Orel
- Department of Gastroenterology, Hepatology and Nutrition, Faculty of Medicine, University Medical Centre Ljubljana, University Children's Hospital, University of Ljubljana, Ljubljana, Slovenia
| | - Marc A Benninga
- Department of Pediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Ilse J Broekaert
- Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Frederic Gottrand
- Pediatric Gastroenterology, Hepatology and Nutrition Department, CHU Lille, University Lille, Lille, France
| | - Alexandra Papadopoulou
- Division of Gastroenterology and Hepatology, First Department of Pediatrics, Children's Hospital "Agia Sofia", University of Athens, Athens, Greece
| | - Carmen Ribes-Koninckx
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, La Fe University Hospital Valencia, Spain
| | - Mike Thomson
- Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, UK
| | - Michael Wilschanski
- Gastroenterology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Nikhil Thapar
- Neurogastroenterology and Motility Unit, Department of Paediatric Gastroenterology, Great Ormond Street Hospital NHS Foundation Trust
- UCL Great Ormond Street Institute of Child Health, London, UK
- Current address: Department of Paediatric Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia
| |
Collapse
|
31
|
Hirsch S, Friedlander JA, Mousa H, Cohran V, Garza JM, Sanghavi R, Ambartsumyan L, Mitchell PD, Rosen R. Comparison of Aerodigestive and Nonaerodigestive Provider Responses to Clinical Case Vignettes. J Pediatr 2021; 232:166-175.e2. [PMID: 33387591 DOI: 10.1016/j.jpeds.2020.12.067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 12/18/2020] [Accepted: 12/22/2020] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To evaluate differences in practice patterns between aerodigestive and nonaerodigestive providers in pediatric gastroenterology when diagnosing and treating common aerodigestive complaints. STUDY DESIGN A questionnaire comprised of clinical vignettes with multiple-choice questions was distributed to both aerodigestive and nonaerodigestive pediatric gastroenterologists. Vignettes focused on management of commonly encountered general gastroenterology and aerodigestive issues, such as gastroesophageal (GE) reflux, aspiration, and feeding difficulties. Tests of equal proportions were used to compare rates of testing and empiric therapy within and across groups. Multivariate analysis was used to assess differences in response rates between aerodigestive and nonaerodigestive providers. RESULTS A total of 88 pediatric gastroenterologists from 18 institutions completed the questionnaire. There were 35 aerodigestive gastroenterology providers and 53 nonaerodigestive gastroenterology providers. The nonaerodigestive group included 31 general gastroenterologists and 22 providers with self-identified subspecialty gastroenterology expertise. Aerodigestive specialists were more likely than nonaerodigestive gastroenterologists to pursue testing over empiric therapy in cases involving isolated respiratory symptoms (P < .05); aerodigestive providers were more likely to recommend pH-impedance testing, videofluoroscopic swallow studies, and upper gastrointestinal barium study (P < .05 for each test) depending on the referring physician. For vignettes involving infant GE reflux, both groups chose empiric treatments more frequently than testing (P < .001), although aerodigestive providers were more likely than nonaerodigestive providers to pursue testing like upper gastrointestinal barium studies (P < .05). CONCLUSIONS Although some practice patterns were similar between groups, aerodigestive providers pursued more testing than nonaerodigestive providers in several clinical scenarios including infants with respiratory symptoms and GE reflux.
Collapse
Affiliation(s)
- Suzanna Hirsch
- Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA
| | | | - Hayat Mousa
- Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA
| | - Valeria Cohran
- Division of Gastroenterology, The Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Jose M Garza
- Division of Gastroenterology, GI Care for Kids, Children's Healthcare of Atlanta, Atlanta, GA
| | - Rinarani Sanghavi
- Division of Gastroenterology, UT Southwestern Medical Center, Children's Medical Center, Dallas, TX
| | | | - Paul D Mitchell
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA
| | - Rachel Rosen
- Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA.
| | | |
Collapse
|
32
|
van der Sande LJTM, Jöbsis Q, Bannier MAGE, van de Garde EMW, Coremans JJM, de Vries F, Dompeling E, Driessen JHM. The risk of community-acquired pneumonia in children using gastric acid suppressants. Eur Respir J 2021; 58:13993003.03229-2020. [PMID: 33737412 DOI: 10.1183/13993003.03229-2020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 02/21/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND With the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)). METHODS We performed a cohort study using data from the UK Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children. RESULTS Current use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90-2.22) and 1.80 (95% CI 1.67-1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months. CONCLUSION The use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.
Collapse
Affiliation(s)
- Linda J T M van der Sande
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Quirijn Jöbsis
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Michiel A G E Bannier
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Ewoudt M W van de Garde
- Dept of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands
| | - Jan J M Coremans
- Dept of Clinical Pharmacy and Toxicology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Frank de Vries
- Dept of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands.,Dept of Clinical Pharmacy and Toxicology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Edward Dompeling
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,E. Dompeling and J.H.M. Driessen are joint senior authors
| | - Johanna H M Driessen
- Dept of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands.,Dept of Clinical Pharmacy and Toxicology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.,E. Dompeling and J.H.M. Driessen are joint senior authors
| |
Collapse
|
33
|
The Safety and Efficacy of Lansoprazole plus Metoclopramide among Neonates with Gastroesophageal Reflux Disease Resistant to Conservative Therapy and Monotherapy: A Clinical Trial. Int J Pediatr 2021; 2021:3208495. [PMID: 33510798 PMCID: PMC7826204 DOI: 10.1155/2021/3208495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 11/18/2020] [Accepted: 01/04/2021] [Indexed: 11/17/2022] Open
Abstract
Background Gastroesophageal reflux disease (GERD) is one of the most common problems in neonates. The main clinical manifestations of neonatal GERD are frequent regurgitation or vomiting associated with irritability, crying, anorexia or feeding refusal, failure to thrive, arching of the back, and sleep disturbance. Aims The efficacy and safety of ranitidine plus metoclopramide and lansoprazole plus metoclopramide in reducing clinical GERD symptoms based on I-GERQ-R scores in neonatal GERD resistant to conservative and monotherapy. Study Design. This study was a randomized clinical trial of term neonates with GERD diagnosis (according to the final version of the I-GERQ-R), resistant to conservative and monotherapy admitted to Bahrami Children Hospital during 2017-2019. Totally, 120 term neonates (mean age 10.91 ± 7.17 days; girls 54.63%) were randomly assigned to a double-blind trial with either oral ranitidine plus metoclopramide (group A) or oral lansoprazole plus metoclopramide (group B). The changes of the symptoms and signs were recorded after one week and one month. At the end, fifty-four neonates in each group completed the study and their data were analyzed. Results There was no significant difference in demographic and baseline characteristics between the two groups. The response rate of "lansoprazole plus metoclopramide" was significantly higher than "ranitidine plus metoclopramide" (7.44 ± 3.86 score vs. 9.3 ± 4.57 score, p = 0.018) after one week and (2.41 ± 3.06 score vs. 4.5 ± 4.12 score, p = 0.003) after one month (primary outcome). There were no drug adverse effects in either group during intervention (secondary outcome). Conclusions The response rate was significant in each group after one week and one month of treatment, but it was significantly higher in the "lansoprazole plus metoclopramide" group compared with the "ranitidine plus metoclopramide" group. The combination of each acid suppressant with metoclopramide led to a higher response rate in comparison with monotherapy used before intervention. This study has been registered at the Iranian Registry of Clinical Trails (RCT20160827029535N3).
Collapse
|
34
|
Zhou Y, Xu L, Wushouer H, Yu A, Xu Z, Chen C, Cui Y, Lu Q, Guan X, Shi L. Acid Suppression Use Among Infants in One Tertiary Children's Hospital in China, 2015-2018: A Retrospective Observational Study. Front Pediatr 2021; 9:679203. [PMID: 34095037 PMCID: PMC8175967 DOI: 10.3389/fped.2021.679203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 04/26/2021] [Indexed: 11/13/2022] Open
Abstract
Clinical guidelines emphasized that physicians should be cautious when prescribing acid suppressions to infants. Histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are not approved for use in infants aged below 2 years in China. We investigated H2RA/PPI use in infants aged below 2 years hospitalized between 1st January 2015 and 31st December 2018 in a Chinese tertiary children's hospital. Our study observed that H2RAs/PPIs were frequently prescribed with a prevalence of 4.4% (7,158/162,192). The frequency of PPI use was over two-fold than that of H2RA use (71.9%, 5,148/7,158; 28.1%, 2,011/7,158). H2RAs/PPIs were commonly used to treat infants without digestive system diseases (57.5%, 4,118/7,158). Further studies are urgently needed to evaluate the effectiveness and safety of H2RAs/PPIs in infants.
Collapse
Affiliation(s)
- Yue Zhou
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Lina Xu
- Department of Pharmacy, Jiangxi Provincial Children's Hospital, Nanchang, China
| | - Haishaerjiang Wushouer
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.,International Research Center for Medicinal Administration (IRCMA), Peking University, Beijing, China
| | - Aichen Yu
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Ziyue Xu
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Chaoyang Chen
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.,Department of Pharmacy, Peking University First Hospital, Beijing, China
| | - Yimin Cui
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.,Department of Pharmacy, Peking University First Hospital, Beijing, China.,Institute of Clinical Pharmacology, Peking University, Beijing, China
| | - Qinghong Lu
- Department of Pharmacy, Jiangxi Provincial Children's Hospital, Nanchang, China
| | - Xiaodong Guan
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.,International Research Center for Medicinal Administration (IRCMA), Peking University, Beijing, China
| | - Luwen Shi
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.,International Research Center for Medicinal Administration (IRCMA), Peking University, Beijing, China
| |
Collapse
|
35
|
Slagter KW, Raghoebar GM, Hamming I, Meijer J, Vissink A. Effect of frenotomy on breastfeeding and reflux: results from the BRIEF prospective longitudinal cohort study. Clin Oral Investig 2020; 25:3431-3439. [PMID: 33315177 PMCID: PMC8137608 DOI: 10.1007/s00784-020-03665-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 10/28/2020] [Indexed: 11/25/2022]
Abstract
Objectives To assess the Efficacy of Frenotomy with regard to Breastfeeding and Reflux Improvement (BRIEF) in infants with breastfeeding problems. Materials and methods A cohort of 175 consecutive breastfeeding women with breastfeeding and reflux problems related to a tongue-tie or lip-tie fulfilling the inclusion criteria was longitudinally followed for 6 months. The effect of frenotomy on these problems was studied by a standardized oral assessment and completing the validated Breastfeeding Self-Efficacy Short Form (BSES-SF), nipple pain score (Visual Analogue Scale, VAS), and Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) questionnaires pre-frenotomy and at 1 week, 1 month, and 6 months’ post frenotomy. Results All 175 women completed the 1-month follow-up and 146 women the 6 months’ follow-up. Frenotomy resulted in a significant improvement of BSES-SF, nipple pain score, and I-GERQ-R after 1 week, which improvement maintained to be significant after 1 month for BSES-SF and I-GERQ-R, and after 6 months for I-GERQ-R. The improvements were irrespective of the type lip-tie or tongue-tie underlying the breast feeding and reflux problems. No post-operative complications were observed. About 60.7% of infants still was breastfed 6 months after treatment. Conclusions Frenotomy is a safe procedure with no post-operative complications and resulting in significant improvement of breastfeeding self-efficacy, nipple pain, and gastro-oesophageal reflux problems. Clinical relevance Frenotomy of a tongue-tie and or lip-tie can lead to improvement of breastfeeding and reflux problems irrespective of the type of tongue-tie or lip-tie and should be considered by clinicians as a proper tool to resolve these problems if non-interventional support did not help. International trial register ISRCTN64428423 Supplementary Information The online version contains supplementary material available at 10.1007/s00784-020-03665-y.
Collapse
Affiliation(s)
- Kirsten W Slagter
- Department of Oral and Maxillofacial Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Gerry M Raghoebar
- Department of Oral and Maxillofacial Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | | | - Jiska Meijer
- General Practitioners Research Institute, Groningen, The Netherlands
| | - Arjan Vissink
- Department of Oral and Maxillofacial Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
| |
Collapse
|
36
|
Use of anti-reflux medications in infants under 1 year of age: a retrospective drug utilization study using national prescription reimbursement data. Eur J Pediatr 2020; 179:1963-1967. [PMID: 33051717 DOI: 10.1007/s00431-020-03837-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 09/30/2020] [Accepted: 10/09/2020] [Indexed: 10/23/2022]
Abstract
Non-specific symptoms such as irritability, vomiting, and back arching during the infant period are often attributed to gastroesophageal reflux. While numerous studies have shown no significant benefit to the use of acid suppressant medications in this population, these medications are frequently prescribed in response to these symptoms. Our goals were to understand how often children were being prescribed this medication. To do this, data was extracted from a national database for reimbursement of prescribed medications through the General Medical Services scheme (GMS). Infants aged less than 1 year and eligible for reimbursement under GMS were included for analysis. A total of 450 infants per 10,000 eligible population received an anti-reflux preparation from the following drug classes (H2 antagonists, proton pump inhibitors, or alginate preparations) in 2018. This is compared with that in 2009 where only 137 per 10,000 eligible infants received these medications. This increase was predominantly attributable to an increase in ranitidine prescriptions.Conclusion: Despite a change in clinical guidelines, anti-reflux preparations are increasingly being prescribed to infants aged less than 1 year. The reasons behind the increase in prescriptions containing these medications cannot be ascertained from this data. This may suggest a proportion of these prescriptions may be unwarranted in this population. What is Known: • The prescription of PPIs in infants has increased in a number of countries. • Use of anti-reflux medications has a very poor evidence base in infancy. What is New: • This data focuses only on an infant age group in a "well" cohort. • Ranitidine may contribute to increased acid-suppressant use in infancy.
Collapse
|
37
|
Perspectives of Parents and Health Care Providers about (Non)Medical Treatment in Infants with Reflux. PHARMACY 2020; 8:pharmacy8040226. [PMID: 33238424 PMCID: PMC7712772 DOI: 10.3390/pharmacy8040226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 11/16/2020] [Accepted: 11/18/2020] [Indexed: 01/29/2023] Open
Abstract
Background: Reflux occurs in 50% of healthy infants at some point. This is most often a physiological condition and does not require drug treatment. Various studies have shown that the use of drugs affecting gastric acidity (DAGAs) in infants is increasing. This entails disadvantages such as unnecessary exposure of infants to medication and their side effects and a higher cost to society. Objective: To get an image of the current practice in Flanders regarding diagnosis and treatment of gastro-oesophageal reflux disease (GORD) in infants and the associated use of DAGAs. To this end, we determined both parents’ and health care providers’ experiences and perceptions about these treatments. Method: An observational cross-sectional study was conducted in April and May 2019. We developed a questionnaire for parents and three different questionnaires for health care providers (HCPs), including midwives, general practitioners, paediatricians and community pharmacists (CPs). The questionnaire for parents was only available through an online platform. HCPs were questioned face-to-face and through an online platform. Results: This study made clear that the counselling of children with GORD is multidisciplinary as the median number of counselling HCPs is 3 (interquartile range (IQR) = 2–4). 63% of the included 251 parents also seek support through online forums and groups. 60% of parents report that no physical tests were performed before DAGAs were prescribed and 39% of parents additionally state they perceived no effect of the prescribed DAGAs. Although parents reported to understand HCPs well (average score 7.4/10), satisfaction with care and information provision was scored lower (between 4.8 and 6.1/10). On the other hand, 234 HCPs answered the questionnaire, of which 89 midwives, 78 community pharmacists and 67 physicians. Only 45 HCPs indicate that guidelines to diagnose or treat GORD are clear. Physicians confirm they perform very little physical testing before starting DAGAs. Provided nonmedical measures to patients are largely in line with the European guidelines, however perceived effectiveness is moderate. Conclusion: Parents are in need for more information about tests, nutrition and (non)medical measures. HCPs on the other hand are in need for clear guidelines on diagnosing and treating GORD.
Collapse
|
38
|
Li Y, Xiong M, Yang M, Wang L, Nie S, Liu D, Pi M, Zhang A, Mao J, Liu HP, Xia H, Xu H, Liu Z, Feng S, Zhou W, Liu X, Yang Y, Tao Y, Feng Y, Chen C, Wang M, Zha Y, Feng JH, Li Q, Ge S, Chen J, He Y, Teng S, Hao C, Liu BC, Tang Y, He W, Hou FF, Xu X. Proton pump inhibitors and the risk of hospital-acquired acute kidney injury in children. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1438. [PMID: 33313183 PMCID: PMC7723554 DOI: 10.21037/atm-20-2284] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 08/21/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND To evaluate the association between use of proton pump inhibitor (PPI) and the risk of hospital-acquired acute kidney injury (HA-AKI) in hospitalized children. METHODS We conducted a multicenter retrospective cohort study in hospitalized children aged 1 month to 18 years from 25 tertiary hospitals across China from 2013 to 2015. Patient-level data were obtained from the electronic hospitalization databases. AKI was defined and staged using the serum creatinine (SCr) data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS Among 42,232 children analyzed, 11,496 (27.2%) used PPI, 1,760 (4.2%) used histamine 2 receptor antagonist (H2RA), and 3,514 (8.3%) had HA-AKI during hospitalization. Over 85% of PPIs were prescribed for prophylaxis of gastro-duodenal lesions in children. The use of PPI was associated with a significantly increased risk of HA-AKI compared with both non-users [odds ratio (OR), 1.37; 95% confidence interval (CI), 1.23-1.53)] and H2RA users (OR, 1.24; 95% CI, 1.01-1.52). The associations were consistent across children of different age range, gender, subtypes of PPIs and methods of administration. A larger effect was observed in children with chronic kidney disease (OR, 3.37; 95% CI, 2.46-4.62) and those needed intensive care (OR, 1.54; 95% CI, 1.33-1.78). The risk of HA-AKI was increased even within the recommended dosage range of PPI. CONCLUSIONS PPIs were widely used and associated with an increased risk of HA-AKI in hospitalized children in China.
Collapse
Affiliation(s)
- Yanqin Li
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Mengqi Xiong
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Minliang Yang
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Long Wang
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Sheng Nie
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Diankun Liu
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Mingjing Pi
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Aihua Zhang
- Children’s Hospital of Nanjing Medical University, Nanjing, China
| | - Jianhua Mao
- Children Hospital of Zhejiang University, Hangzhou, China
| | - Hai-Peng Liu
- Anhui Institute of Pediatric Research, Anhui Provincial Children’s Hospital, Hefei, China
| | - Huimin Xia
- Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Hong Xu
- Children’s Hospital of Fudan University, Shanghai, China
| | - Zhangsuo Liu
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shipin Feng
- Chengdu Women and Children’s Central Hospital, Chengdu, China
| | - Wei Zhou
- Shanghai Children’s Medical Center, Shanghai Jiao Tong University, Shanghai, China
| | | | - Yonghong Yang
- Pediatric Medical Research Center, Gansu Province Child’s Hospital, Lanzhou University Second Hospital, Lanzhou, China
| | - Yuhong Tao
- West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yunlin Feng
- Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Chunbo Chen
- Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Mo Wang
- Children’s Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Zha
- Guizhou Provincial People’s Hospital, Guizhou University, Guiyang, China
| | - Jian-Hua Feng
- The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Qingchu Li
- Guilin Medical University Affiliated Hospital, Guilin, China
| | - Shuwang Ge
- Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jianghua Chen
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Yongcheng He
- Center for Nephrology and Urology Shenzhen University, the First Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, China
| | - Siyuan Teng
- The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | | | - Bi-Cheng Liu
- Institute of Nephrology, Zhong Da Hospital, Nanjing, China
| | - Ying Tang
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenjuan He
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fan Fan Hou
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xin Xu
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
39
|
Calcium and phosphorus bioaccessibility from different amino acid-based medical nutrition formulas for infants and children under in vitro digestive conditions. CLINICAL NUTRITION EXPERIMENTAL 2020. [DOI: 10.1016/j.yclnex.2020.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
|
40
|
Pasman EA, Ong B, Witmer CP, Nylund CM. Proton Pump Inhibitors in Children: the Good, the Bad, and the Ugly. Curr Allergy Asthma Rep 2020; 20:39. [PMID: 32524278 DOI: 10.1007/s11882-020-00926-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW The evidence supporting or contesting the prescription of proton pump inhibitors (PPIs) for children and updates on side effects are reviewed. RECENT FINDINGS PPIs remain an important therapeutic option for esophagitis and gastritis. However, recent studies demonstrate no benefit when prescribing PPIs for chronic cough, infantile reflux, asthma, or functional gastrointestinal disorders. Recent studies suggest adverse effects on microbiome diversity and immune function, resulting in increased rates of gastrointestinal infections, bone fractures, and atopic disorders. PPIs influence a variety of cell types within the in the innate and adaptive immune systems. PPI prescriptions in children may be indicated for select conditions; however, multiple side effects and immune effects have been described. While most of these side effects are rare and mild, some studies suggest enduring adverse effects. Future studies to elucidate the mechanism behind some of these immune and infectious complications will be beneficial.
Collapse
Affiliation(s)
- Eric A Pasman
- Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Bruce Ong
- Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD, USA
- Department of Allergy and Immunology, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Claire P Witmer
- Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD, USA
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
| | - Cade M Nylund
- Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, MD, USA.
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
| |
Collapse
|
41
|
Dziechciarz P, Krenke K, Szajewska H, Horvath A. Lactobacillus rhamnosus GG Usage in the Prevention of Gastrointestinal and Respiratory Tract Infections in Children with Gastroesophageal Reflux Disease Treated with Proton Pump Inhibitors: A Randomized Double-Blinded Placebo-Controlled Trial. Pediatr Gastroenterol Hepatol Nutr 2020; 23:251-258. [PMID: 32483546 PMCID: PMC7231745 DOI: 10.5223/pghn.2020.23.3.251] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 12/17/2019] [Accepted: 02/11/2020] [Indexed: 01/25/2023] Open
Abstract
PURPOSE Proton-pump inhibitors (PPIs) are frequently used to treat gastroesophageal reflux disease (GERD) in children, but recent evidence suggests a potential association between PPI treatment and some types of infections. The aim of this study was to assess the effectiveness of Lactobacillus rhamnosus GG (LGG) for the prevention of gastrointestinal and respiratory tract infections in children with GERD treated with PPI (omeprazol). METHODS Children younger than 5 years with GERD were assigned by a computer-generated list to receive LGG (109 colony-forming units) or placebo, twice daily, concomitantly with PPI treatment for 4-6 weeks; they were followed up for 12 weeks after therapy. The primary outcome measures were the percentage of children with a minimum of one episode of respiratory tract infection and the percentage of children with a minimum of one episode of gastrointestinal infection during the study. RESULTS Of 61 randomized children, 59 patients (LGG n=30; placebo n=29, mean age 11.3 months) were analyzed. There was no significant difference found between the LGG and placebo groups, either for the proportion of children with at least one respiratory tract infection (22/30 vs. 25/29, respectively; relative risk [RR] 0.85, 95% confidence interval [CI] 0.66-1.10) or for the proportion of children with at least one gastrointestinal infection (9/30 vs. 9/29, respectively; RR 0.97, 95% CI 0.45-2.09). CONCLUSION LGG was not effective in the prevention of infectious complications in children with GERD receiving PPI. Caution is needed in interpreting these results, as the study was terminated early due to slow subject recruitment.
Collapse
Affiliation(s)
- Piotr Dziechciarz
- Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland
| | - Katarzyna Krenke
- Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland
| | - Hania Szajewska
- Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland
| | - Andrea Horvath
- Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland
| |
Collapse
|
42
|
Curien-Chotard M, Jantchou P. Natural history of gastroesophageal reflux in infancy: new data from a prospective cohort. BMC Pediatr 2020; 20:152. [PMID: 32264869 PMCID: PMC7137340 DOI: 10.1186/s12887-020-02047-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 03/25/2020] [Indexed: 12/17/2022] Open
Abstract
Background Gastroesophageal reflux (GER) is common in infants. Gastroesophageal reflux disease (GERD) is defined as GER leading to troublesome symptoms that affect daily functioning and/or complications. This study is aimed at determining the prevalence and progression of GER and GERD in a cohort of healthy term infants from birth to 12 months old. Methods We conducted a prospective cohort study including all full-term living neonates born at Besançon Teaching Hospital, France. Parents completed a clinical report form and the Infant Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R) at 1, 3, 6, 10, and 12 months of age. GER was defined as score ≥ 1 to the first question with I-GERQ-R score < 16, and GERD as score ≥ 1 to the first question with I-GERQ-R score ≥ 16. Regurgitation was based on the answer to the first question of the I-GERQ-R as anything coming out of the mouth daily. Results 157/347 births were included (83 boys). The prevalence of regurgitation at least once a day was 45.7% overall. In total: 72, 69, 56, 18, and 13% of infants regurgitated at least once a day at 1, 3, 6, 10, and 12 months of age, respectively. Physiological GER affected 53, 59, 51, 16, and 12% of infants; GERD, 19, 9, 5, 2, and 2%, respectively. Two risk factors were identified: family history of GER and exposure to passive smoking. Treatment included dietary modification (14%) and pharmacotherapy (5%). Conclusion Physiological GER peaked at 3 months, GERD at 1 month. Most cases resolved on their own. GER and GERD are very common in the infant’s population and parents should be reassured/educated regarding symptoms, warning signs, and generally favorable prognosis. I-GERQ-R is useful to the clinical screening and follow up for GER and GERD.
Collapse
Affiliation(s)
- Marlène Curien-Chotard
- Pediatric Unit, Besançon Teaching Hospital , 3 Boulevard Alexandre Fleming, 25000, Besançon, France.
| | - Prévost Jantchou
- CHU Sainte-Justine. 3175 Côte Sainte Catherine, H3T IC5, Montréal, Québec, Canada.,Université de Montreal, Montreal, Canada
| |
Collapse
|
43
|
Incidence of Gastroesophageal Reflux Disease in Children With Cleft Lip and Palate and an Evaluation of Its Impact on Weight Gain. Ann Plast Surg 2020; 85:S141-S142. [PMID: 32149845 DOI: 10.1097/sap.0000000000002340] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Patients with cleft lip and/or palate have higher rates of failure to thrive (FTT), decreased growth, and more often experience feeding difficulties as compared with the general pediatric population (J Child Health Care. 2014;18:72-83). Although insufficient nursing, excessive air intake, and incorrect feeding methods have been established in the literature, the role of gastroesophageal reflux disease (GERD) as a contributing factor in cleft patients has not been thoroughly examined. Presently, there is a paucity of literature analyzing the incidence and effect of GERD on this unique population. Furthermore, no studies have evaluated the effect of GERD therapy on improvement of weight gain and FTT in cleft patients. The purpose of this retrospective review was to identify the incidence of GERD in the orofacial cleft population and to see if appropriate treatment was effective in improving weight gain. Fifty patients with cleft lip, cleft lip and palate, and isolated cleft palate were identified from a single surgeon's experience at a large academic medical center from 2015 to 2019. The data show that a significantly higher percentage of patients with cleft lip/and or palate have clinical evidence of GERD, which required treatment as compared with published reports of less than 1% in the noncleft population. The data also suggest that the patients diagnosed with GERD who received pharmacologic treatment showed improved weight gain as compared with those who did not. Given our findings, the diagnosis of GERD should be considered in orofacial cleft patients exhibiting signs of feeding difficulty or those with FTT. The early diagnosis and treatment of GERD in patients with orofacial clefts may improve weight gain.
Collapse
|
44
|
Xu X, Zhang L, Cai Y, Liu D, Shang Z, Ren Q, Li Q, Zhao W, Chen Y. Inhibitor discovery for the E. coli meningitis virulence factor IbeA from homology modeling and virtual screening. J Comput Aided Mol Des 2019; 34:11-25. [PMID: 31792885 DOI: 10.1007/s10822-019-00250-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 11/08/2019] [Indexed: 11/28/2022]
Abstract
Escherichia coli (E. coli) K1 is the most common Gram-negative bacteria cause of neonatal meningitis. The penetration of E. coli through the blood-brain barrier is a key step of the meningitis pathogenesis. A host receptor protein, Caspr1, interacts with the E. coli virulence factor IbeA and thus facilitates bacterial penetration through the blood-brain barrier. Based on this result, we have now predicted the binding pattern between Caspr1 and IbeA by an integrated computational protocol. Based on the predicted model, we have identified a putative molecular binding pocket in IbeA, that directly bind with Caspr1. This evidence indicates that the IbeA (229-343aa) region might play a key role in mediating the bacteria invasion. Virtual screening with the molecular model was conducted to search for potential inhibitors from 213,279 commercially available chemical compounds. From the top 50 identified compounds, 9 demonstrated a direct binding ability to the residues within the Caspr1 binding site on IbeA. By using human brain microvascular endothelial cells (hBMEC) with E. coli strain RS218, four molecules were characterized that significantly attenuated the bacteria invasions at concentrations devoid of cell toxicity. Our study provides useful structural information for understanding the pathogenesis of neonatal meningitis, and have identified drug-like compounds that could be used to develop effective anti-meningitis agents.
Collapse
Affiliation(s)
- Xiaoqian Xu
- Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
| | - Li Zhang
- Department of Life Science, Liaoning University, Shenyang, China
| | - Ying Cai
- Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China
| | - Dongxin Liu
- Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China
| | - Zhengwen Shang
- Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China
| | - Qiuhong Ren
- Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China
| | - Qiong Li
- Department of Life Science, University of Science and Technology of China, Hefei, China
| | - Weidong Zhao
- Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China
| | - Yuhua Chen
- Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
| |
Collapse
|
45
|
Bernal CJ, Aka I, Carroll RJ, Coco JR, Lima JJ, Acra SA, Roden DM, Van Driest SL. CYP2C19 Phenotype and Risk of Proton Pump Inhibitor-Associated Infections. Pediatrics 2019; 144:e20190857. [PMID: 31699831 PMCID: PMC6889971 DOI: 10.1542/peds.2019-0857] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/22/2019] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVES Proton pump inhibitors (PPIs) are often used in pediatrics to treat common gastrointestinal disorders, and there are growing concerns for infectious adverse events. Because CYP2C19 inactivates PPIs, genetic variants that increase CYP2C19 function may decrease PPI exposure and infections. We tested the hypothesis that CYP2C19 metabolizer phenotypes are associated with infection event rates in children exposed to PPIs. METHODS This retrospective biorepository cohort study included individuals aged 0 to 36 months at the time of PPI exposure. Respiratory tract and gastrointestinal tract infection events were identified by using International Classification of Diseases codes in the year after the first PPI mention. Variants defining CYP2C19 *2, *3, *4, *8, *9, and *17 were genotyped, and all individuals were classified as CYP2C19 poor or intermediate, normal metabolizers (NMs), or rapid or ultrarapid metabolizers (RM/UMs). Infection rates were compared by using univariate and multivariate analyses. RESULTS In all, 670 individuals were included (median age 7 months; 44% girls). CYP2C19 NMs (n = 267; 40%) had a higher infection rate than RM/UMs (n = 220; 33%; median 2 vs 1 infections per person per year; P = .03). There was no difference between poor or intermediate (n = 183; 27%) and NMs. In multivariable analysis of NMs and RM/UMs adjusting for age, sex, PPI dose, and comorbidities, CYP2C19 metabolizer status remained a significant risk factor for infection events (odds ratio 0.70 [95% confidence interval 0.50-0.97] for RM/UMs versus NMs). CONCLUSIONS PPI therapy is associated with higher infection rates in children with normal CYP2C19 function than in those with increased CYP2C19 function, highlighting this adverse effect of PPI therapy and the relevance of CYP2C19 genotypes to PPI therapeutic decision-making.
Collapse
Affiliation(s)
| | | | | | | | - John J Lima
- Center for Pharmacogenomics and Translational Research, Nemours Children's Health System, Jacksonville, Florida
| | | | - Dan M Roden
- Biomedical Informatics
- Medicine, and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee; and
| | | |
Collapse
|
46
|
Schwartz NRM, Hutfless S, Herrinton LJ, Amsden LB, Fevrier HB, Giefer M, Lee D, Suskind DL, Delaney JAC, Phipps AI. Proton Pump Inhibitors, H 2 Blocker Use, and Risk of Inflammatory Bowel Disease in Children. J Pediatr Pharmacol Ther 2019; 24:489-496. [PMID: 31719810 DOI: 10.5863/1551-6776-24.6.489] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Evidence suggests use of proton pump inhibitors (PPIs) and H2 blockers may provoke disease flares in individuals with established inflammatory bowel disease (IBD); however, there are no studies investigating the relationship of these medications with risk of developing pediatric IBD. The hypothesis was that use of acid suppression therapy in children might be associated with development of pediatric IBD. METHODS This was a nested case-control study of 285 Kaiser Permanente Northern California members, age ≤21 years diagnosed with IBD from 1996 to 2016. Four controls without IBD were matched to each case on age, race, and membership status at the case's index date. Disease risk scores (DRS) were computed for each subject. Odds ratios and 95% confidence intervals were calculated by using conditional logistic regression models adjusted for DRS. RESULTS The children's mean age was 15.1 ± 2.6 years and 49.5% were female. Six cases (n = 3 Crohn's disease [CD], n = 3 ulcerative colitis [UC]) and 6 controls were prescribed PPIs and 10 cases (n = 7 CD, n = 3 UC) and 28 controls were prescribed H2 blockers. The OR for the association of at least 1 PPI or H2 blocker prescription with subsequent IBD was 3.6 (95% CI, 1.1-11.7) for PPIs and 1.6 (95% CI, 0.7-3.7) for H2 blockers. CONCLUSIONS Early-life PPI use appears to be associated with subsequent IBD risk. These findings have implications for clinical treatment of children with gastrointestinal symptoms and warrant further investigation in a larger cohort.
Collapse
|
47
|
Duncan DR, Mitchell PD, Larson K, McSweeney ME, Rosen RL. Association of Proton Pump Inhibitors With Hospitalization Risk in Children With Oropharyngeal Dysphagia. JAMA Otolaryngol Head Neck Surg 2019; 144:1116-1124. [PMID: 30325987 DOI: 10.1001/jamaoto.2018.1919] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Importance Proton pump inhibitors (PPI) are commonly prescribed to children with oropharyngeal dysphagia and resultant aspiration based on the assumption that these patients are at greater risk for reflux-related lung disease. There is little data to support this approach and the potential risk for increased infections in children treated with PPI may outweigh any potential benefit. Objective The aim of this study was to determine if there is an association between hospitalization risk in pediatric patients with oropharyngeal dysphagia and treatment with PPI. Design, Setting, and Participants We performed a retrospective cohort study to compare the frequency and length of hospitalizations for children who had abnormal results on videofluoroscopic swallow studies that were performed between January 1, 2015, and December 31, 2015, and who were or were not treated with PPI, with follow-up through December 31, 2016. Records were reviewed for children who presented for care at Boston Children's Hospital, a tertiary referral center. Participants included 293 children 2 years and younger with evidence of aspiration or penetration on videofluoroscopic swallow study. Exposures Groups were compared based on their exposure to PPI treatment. Main Outcomes and Measures The primary outcomes were hospital admission rate and hospital admission nights and these were measured as incident rates. Multivariable analyses were performed to determine predictors of hospitalization risk after adjusting for comorbidities. Kaplan-Meier curves were created to determine the association of PPI prescribing with time until first hospitalization. Results A total of 293 patients with a mean (SD) age of 8.8 (0.4) months and a mean (SD) follow-up time of 18.15 (0.20) months were included in the analysis. Patients treated with PPI had higher admission rates (Incidence rate ratio [IRR], 1.77; 95% CI, 1.16-2.68) and admission nights (IRR, 2.51; 95% CI, 1.36-4.62) even after adjustment for comorbidities. Patients with enteral tubes who were prescribed PPIs were at the highest risk for admission (hazard ratio [HR], 2.31; 95% CI, 1.24-4.31). Conclusions and Relevance Children with aspiration who are treated with PPI have increased risk of hospitalization compared with untreated patients. These results support growing concern about the risks of PPI use in children.
Collapse
Affiliation(s)
- Daniel R Duncan
- Aerodigestive Center, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts
| | - Paul D Mitchell
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Massachusetts
| | - Kara Larson
- Aerodigestive Center, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts
| | - Maireade E McSweeney
- Aerodigestive Center, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts
| | - Rachel L Rosen
- Aerodigestive Center, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts
| |
Collapse
|
48
|
Sears K, Elms S, Whitehead M, Tranmer JE, Edge DS, VanDenKerkhof EG. A population-based study of prescribing trends in a potentially vulnerable paediatric population from 1999 to 2012. INTERNATIONAL JOURNAL OF PHARMACY PRACTICE 2019; 27:545-554. [PMID: 31373071 DOI: 10.1111/ijpp.12565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 05/20/2019] [Accepted: 07/03/2019] [Indexed: 11/28/2022]
Abstract
OBJECTIVES There is a limited understanding of paediatric medication prescribing trends and patterns, thus poorly positioning decision-makers to identify quality and safety concerns related to medication use. The objective of this study was to determine overall medication prescribing trends and patterns among children receiving Ontario Drug Benefits over a thirteen-year period in the province of Ontario, Canada. METHODS Administrative health databases housed within the Institute for Clinical Evaluative Sciences (ICES), Ontario, Canada, were used to identify outpatient prescriptions dispensed from 1999 to 2012 through a publicly funded programme to children ≤18 years of age. Medications were classified according to the American Hospital Formulary Service Pharmacologic-Therapeutic Classification system. Descriptive statistics were used to summarize prescribing patterns. KEY FINDINGS This study identified 457 037 children who were dispensed a new prescription between 1999 and 2012. About 56% received their first prescription before 6.5 years of age, and 85% of the children in this study were from families who received social assistance. The most commonly prescribed drugs were antiinfectives (56.1%). Prescriptions for several central nervous system agents, including antipsychotics and agents for attention-deficit/hyperactivity disorder, increased across the study period. Changes in prescribing patterns within opioids, hormones and autonomic agents were noted. The results suggest that historically, prescribing trends have shifted with public policy, pharmaceutical marketing and diagnostic patterns, thus identifying them as a possible tool to measure the impact of policydriven practice changes. Anti-infective prescribing increased markedly with the global H1N1 pandemic. Pharmaceutical marketing, formulary decisions and diagnostic trends may affect the prescribing of ADHD medications globally. The prescribing of codeine-containing products and medroxyprogesterone appeared to fluctuate in response to important publications in the medical literature, and the use of epinephrine syringes increased after public policy changes in the province of Ontario. The steady rise in the use of medications whose long-term effects in children are unknown, such as antipsychotics and proton pump inhibitors, identifies areas in need of future research. CONCLUSIONS This study presents the first overview of Canadian prescribing trends for children, the majority of which are of low socioeconomic status and represent a potentially vulnerable population. Our analysis suggests that future research is required to determine whether prescribing trends could be used as indicators of policy effectiveness, pharmacovigilance and diagnostic trends.
Collapse
Affiliation(s)
- Kim Sears
- School of Nursing, Queen's University, Kingston, ON, Canada
| | - Sherri Elms
- School of Nursing, Queen's University, Kingston, ON, Canada
| | - Marlo Whitehead
- Institute for Clinical Evaluative Sciences, Queen's University, Kingston, ON, Canada
| | - Joan E Tranmer
- School of Nursing, Queen's University, Kingston, ON, Canada.,Institute for Clinical Evaluative Sciences, Queen's University, Kingston, ON, Canada
| | - Dana S Edge
- School of Nursing, Queen's University, Kingston, ON, Canada
| | - Elizabeth G VanDenKerkhof
- School of Nursing, Queen's University, Kingston, ON, Canada.,Institute for Clinical Evaluative Sciences, Queen's University, Kingston, ON, Canada
| |
Collapse
|
49
|
Malchodi L, Wagner K, Susi A, Gorman G, Hisle-Gorman E. Early Acid Suppression Therapy Exposure and Fracture in Young Children. Pediatrics 2019; 144:peds.2018-2625. [PMID: 31175146 DOI: 10.1542/peds.2018-2625] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/29/2019] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Acid suppression therapy (AST), including proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs), is frequently prescribed to treat symptomatic gastroesophageal reflux in otherwise healthy infants. PPI use has been associated with increased fracture risk in older adults; 2 preliminary studies in children have conflicting results. METHODS A retrospective cohort of children born 2001 to 2013 who were followed for ≥2 years was formed. Those with osteogenesis imperfecta, cholestasis, or child maltreatment were excluded. Prescription data were used to identify AST prescription before age 1 year. International Classification of Diseases, Ninth Revision, Clinical Modification codes identified fractures after age 1 year. A Cox proportional hazard analysis assessed fracture hazard and was adjusted for sex, prematurity, low birth weight, previous fracture, anti-epileptics, and overweight or obesity. RESULTS Of 851 631 included children, 97 286 (11%) were prescribed AST in the first year of life; 7998 (0.9%) children were prescribed PPI, 71 578 (8%) were prescribed H2RA, and 17 710 (2%) were prescribed both a PPI and H2RA. Infants prescribed AST had an earlier median first fracture age (3.9 vs 4.5 years). After adjustment, increased fracture hazard was associated with PPI use (21%) and PPI and H2RA use (30%), but not H2RA use alone. Longer duration of AST treatment and earlier age of first AST use was associated with increased fracture hazard. CONCLUSIONS Infant PPI use alone and together with H2RAs is associated with an increased childhood fracture hazard, which appears amplified by days of use and earlier initiation of ASTs. Use of AST in infants should be weighed carefully against possible fracture.
Collapse
Affiliation(s)
- Laura Malchodi
- Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, Maryland.,Pediatrics, D 35th Medical Group, Misawa Air Force Base, Misawa, Japan; and
| | - Kari Wagner
- Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, Maryland.,Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Apryl Susi
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Gregory Gorman
- Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, Maryland.,Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | - Elizabeth Hisle-Gorman
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland
| |
Collapse
|
50
|
Acid Suppression in Neonates: Friend or Foe? Indian Pediatr 2019. [DOI: 10.1007/s13312-019-1549-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|