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Context 1
... scenario in the USA appears to be different: three out of five compounds (omeprazole, esomeprazole, lansoprazole) are currently authorised for children, although with the exclusion of infant and neonate age groups (Table 1). It is noteworthy that lansoprazole and esomeprazole are approved for children aged 1-17 in the USA but not in the EU. ...Similar publications
Little is known about the food preferences of children with a feeding disorder and medical diagnoses. Therefore, we conducted repeated paired-stimulus-preference assessments with foods to which we either exposed or did not expose 3 children with a feeding disorder and medical diagnoses during clinical treatment. Responding was relatively equivalent...
Citations
... GERD mainly requires short-term treatment 28 and occurs more often in the youngest children (younger than 1 year) and oldest children (older than 11 years). 26 This is supported by our findings, where the highest prevalence and incidence rates were observed among the youngest age groups (0-1 year; supported by supplementary analyses) and the oldest age groups (age: [11][12][13][14][15][16][17]. Similarly, the proportion of children staying on PPI for at least 1 year is close to 0 for children older than 5 years and around 3% for the youngest (0-4 years). ...
Objectives
Proton pump inhibitors (PPI) are among the most frequently used drugs in the developed countries. In recent years, their use among children and adolescents has been on the increase. Guidelines recommend use for a period no longer than 4‐8 weeks. The aim of this study was to describe time trends in prescribing patterns of PPI use among children, with emphasis on persistence to therapy.
Methods
We used the Danish nationwide health care registries, and identified all Danish children (0‐17 years old) who were provided with a filled in PPI prescription between 2000 and 2015. Based on descriptive analyses, we reported trends over time in annual use, prevalent and incident users. Moreover, we evaluated persistence to treatment and doses used over time. Analyses were stratified by age groups (0‐4, 5‐11 and 12‐17 years).
Results
We identified 212,056 filled in PPI prescriptions prescribed to 78,489 children. The total annual use of PPIs among children increased eightfold from 2000 to 2015. Omeprazole was most frequently used (60% of all use). The proportion of prevalent users increased from 0.1 in 2000 to 3.1 per 1000 children in 2015, while the rate of new users increased from 1.2 to 8.0 per 1000 child years. In general, persistence to PPIs was low: in the youngest age groups (14%), slightly more children were covered by treatment 12 months after the first prescription compared with the oldest age groups (5%).
Conclusion
The use of PPIs among Danish children has increased substantially during the last 15 years. In general, treatment with PPIs among children was of short duration. Attention should be paid to indications and rationality behind initiation of therapy.
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... The discrepancies of information about drug use in neonatology between ANVISA and FDA identified in this study allow us to speculate whether the high rate of off-label drug use in neonates reflects the lack of studies in this age group or whether it occurs because the results of a few published studies are not reflected in the drug label. It is likely that a combination of the two theories has merit (Allegaert, Tibboel, van den Anker, 2013;Jacqz-Aigrain et al., 2013;Lass et al., 2011;Tafuri et al., 2009). ...
This study was designed to investigate the use of off-label and unlicensed drugs in a Neonatal Care Unit (NCU) and to compare the frequency of use of off-label drugs according to the drug regulatory agencies in Brazil (Agência Nacional de Vigilância Sanitária-ANVISA) and the United States Food and Drug Administration (FDA). A prospective observational study was carried out in the NCU. Prescriptions were classified as off-label and unlicensed using both ANVISA and FDA criteria. A total of 157 newborns and 1187 prescriptions were analyzed. The most prescribed drug was fentanyl (9.3%), followed by multivitamin (8.4%) and gentamicin (7.9%). According to ANVISA criteria, there were 665 (56.0%) off-label prescriptions and 86 (7.2%) unlicensed prescriptions and 95.5% of newborns received at least one drug off-label. By contrast, according to FDA criteria, there were 592 (49.9%) off-label prescriptions and 84 (7.1%) unlicensed prescriptions, and 72.0% of newborns received at least one drug off-label. The off-label use of drugs registered by ANVISA differed significantly from that of drugs registered by the FDA. There was a high frequency of off-label and unlicensed drug use in the investigated NCU, and there was an inverse relationship between off-label and unlicensed usage and the gestational age of the newborns.
... 12 Concerns regarding the safety and efficacy of off-label prescribing had always been raised by the public and by healthcare practitioners as well. 13 In Jordan, such concerns have been mostly raised by paediatricians who specialize in infectious diseases, as the use of antibiotics in children has its own set of risks and efficacy concerns. 9 In a previous study that explored the perceptions and attitudes of Jordanian paediatricians toward off-label prescribing, paediatricians who specialized in infectious diseases reported high familiarity levels with the term 'off-label prescribing' indicating that such use of medicines in children is prevalent, hence paediatricias will work to ensure a balance between the safety and efficacy of antibiotics prescribed for children and under the pressures of growing bacterial resistance to antibiotics which may lead them to increasingly rely on off-label prescribing. ...
Objective: The aim of the present study was to evaluate the use of off-label antibiotics in neonatal intensive care units (NICUs) and paediatric wards in Jordan.
Methods: Data of patients admitted to the neonatal intensive care units and paediatric wards in King Abdulla University Hospital were collected over an 8-week survey between May and July 2012. Data collected in this study included patients’ age, weight, medical history, diagnosis and the details of antibiotics prescribed to each patient.
Results: The study involved a total of 250 children (80 admitted to the NICU and 170 admitted to the wards). A total of 598 antibiotic prescriptions were issued for these patients (244 in NICUs and 354 in paediatricwards). The results of the present study show that off-label antibiotic prescribing to paediatric patients is very common. Off-label antibiotic prescribing to paediatric patients is related mostly to doses and indications, and rarely to age. The majority of admitted patients received at least one off-label antibiotic during their hospital stay.
Conclusion: This study reveals the high prevalence of off-label use of antibiotic among paediatric children in Jordan. There is a serious need for robust and continuous educational programs to improve the awareness of paediatricians of guidelines surrounding the use of antibiotics in paediatric patients. Furthermore, true collaboration between paediatricians and clinical pharmacists towards safe and effective antibiotic prescribing in paediatric patients is crucial.
... [13][14][15][16] Evidence suggests that as a result, physicians are prescribing medications in this unapproved age group for the treatment of GORD ('off-label'), in increasingly large numbers when they are able to access formulations. 17,18 A retrospective study of infants in the United States reported a 7.5-fold increase in PPI use between 1999 and 2004. 18 More recent research examining physician prescribing behaviours has revealed an 11-fold increase in the number of new prescriptions for PPIs in patients aged less than 12 months. ...
The aim of this study was to evaluate the attitudes and practices of Australian general practitioners (GPs) regarding infant gastro-oesophageal reflux disease (GORD) diagnosis and management.
A national cross-sectional survey, involving a random sample of currently practising Australian GPs (n = 2319) was undertaken between July and September 2011. GPs attitudes and management of infant GORD were surveyed via an online and paper-based 41-item questionnaire.
In total, 400 responses were analysed (17.24% response rate). The majority of GPs employed empirical trials of acid-suppression medication and/or lifestyle modifications to diagnose infant GORD. GPs frequently recommended dietary modification despite the belief that they were only moderately effective at best. In addition, GPs frequently prescribed acid-suppression medication, despite concerns regarding their safety in the infant population. Other GP concerns included the lack of clinical guidelines and education for GPs about infant GORD, as well as the level of evidence available for the safety and efficacy of diagnostic tests and treatments.
Despite the important role Australian GPs play in the diagnosis and management of infant GORD, high-level evidence-based guidelines for GPs are lacking. Consequently, GPs engage in diagnostic and management practices despite their concerns regarding the safety and effectiveness.
© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
... Similar to Tafuri et al. [29], our results raise the question of whether the high rate of off-label use in neonates is a reflection of the very few neonatal studies that have been performed or is it that the results of these studies are simply not reflected in the SPCs. Most likely it is a combination of both, a conclusion supported by the fact that for some commonly used agents, such as gentamicin, neonatal information is lacking in the SPC but is available in other sources. ...
To characterise neonatal hospital drug use and to compare the availability of drug information between Estonian Summaries of Product Characteristics (SPCs) and other sources.
This was a prospective cohort study in which pharmacotherapy information on neonates admitted to Tartu University Clinics between 1 February and 1 August 2008 and to Tallinn Children's Hospital between 1 February and 1 August 2009 was collected. Drug labelling status was determined according to Estonian SPCs, and neonatal information was compared with the British National Formulary for Children (BNFC) and the Thomson Micromedex database.
Of 490 hospitalised neonates, 71% received pharmacotherapy. Within the entire study period, there were 1981 prescriptions for 115 products, with a median of four (interquartile range 2-7) products per child. Antibacterial, cardiovascular and central nervous system drugs were the most commonly prescribed. All treated preterm neonates received at least one unlicensed or age-related off-label prescription. All prescriptions for alimentary, genitourinary, musculoskeletal and sensory system drugs were off-label. There were large differences in the neonatal information provided by the different sources, with the largest differences found for term neonates, for whom the information was available for 67, 38 and 24% of prescriptions according to the BNFC, Micromedex and Estonian SPC, respectively.
The high rate of age-related off-label prescribing for neonates calls for urgent action from medical professionals and others to reinforce effective and safe pharmacotherapy for this age group. The existing SPCs should be regularly updated and more closely harmonised to each other.
... It has been reported that at least 30% of neonates received treatment with gastric acidity inhibitors at the time of discharge from NICU [70]. With regard to PPIs, through a study conducted by Tafuri et al. [71], after upgrading EU-DRANET databases and FDA web-site, 19 pediatric studies involving the use of PPIs in GERD were selected. Available data of pharmacokinetics, efficacy and profile safety were analyzed. ...
Gastroesophageal reflux (GER) is defined as the passage of gastric contents into the esophagus. It occurs in healthy infants and can be considered physiological process. Uncomplicated GER can present with recurrent vomiting or regurgitation without any other symptoms and is usually managed by educating, reassuring, and guiding the parent without other intervention. GER disease (GERD) refers to the appearance of troublesome symptoms or complications (erosive esophagitis, ulceration, Barrett's esophagus) and may warrant acid suppression. Proton Pump Inhibitors (PPIs) are the most effective pharmacologic agents available for the treatment of children with GERD. In the pediatric practice only omeprazole, lansoprazole and esomeprazole are available over the first year of life. The empiric use in infants with nonspecific symptoms (excessive crying, regurgitation, feeding refusal, chronic cough) is frequent without randomized controlled study. Our paper will focus on the correct indications, dosages, duration of treatment and safety of PPI use in pediatric population.
... An extensive literature documents the practice and disadvantages of off-label prescription drug use in children. [2][3][4][5][6][7] Approximately 75% of all FDAapproved medications licensed since the early 1970s have limited or no labeling for children; therefore, by necessity many medications are utilized off-label in children. 8,9 This practice is not unique to pediatrics. ...
A substantial unmet medical device need exists in pediatric care. As a result, the off-label use of approved devices is routine in pediatric interventional cardiology, but the extent and nature of this practice has not been previously described. The purpose of this study, therefore, is to evaluate the prevalence and nature of off-label cardiac device use in an active pediatric interventional program in the United States.
This study is a retrospective review of all interventional cardiac procedures performed at our institution from July 1, 2005 to June 30, 2008. Diagnostic (noninterventional) catheterizations, myocardial biopsies, invasive electrophysiology studies, and studies involving investigational devices were excluded. Interventions performed were compared with the manufacturer's labeled indications for each device.
During this 3-year period, 473 patients (median age 4.1 years) underwent 595 transcatheter interventions. An approved device was utilized for an off-label application in 63% of patients, and in 50% of all interventions performed. The most frequent off-label procedures were stent implantations (99% off-label), balloon dilations (78% off-label), and coil embolizations (29% off-label). In contrast, the off-label use of septal and ductal occluders was relatively uncommon.
In our routine (noninvestigational) practice of pediatric interventional cardiology, 63% of patients underwent procedures utilizing medical devices for off-label indications. These data underscore the need to enhance cardiac device review and approval processes in the United States to include pediatric applications.
Hintergrund und Ziele Kinder und Jugendliche sind bei der Arzneimittelanwendung aufgrund ihrer entwicklungsphy-siologischen Besonderheiten und einer vergleichsweise häufigen off-label-Anwendung einem erhöhten Risiko für unerwünschte Arzneimittelereignisse (UAE) ausgesetzt. Um UAE leichter erkennen zu können, wurden sogenannte Trigger Tools entwickelt, die bei der Durchsicht von Patientenakten ohne relevanten Mehraufwand angewendet werden. Mit ihrem checklistenarti-gen und einfachen Aufbau unterstützen sie Pharmakovigilanz-Aktivitäten und sind zugleich kostengünstig. Das Auftreten eines bestimmten Signalwortes (Triggers) indiziert einen UAE-Verdacht. Die meisten dieser Tools sind jedoch auf die erwachsene Patientengruppe ausge-richtet. Weil UAE in der Pädiatrie jedoch anders ausgeprägt sein können und zudem pädiat-riespezifische Wirkstoffe berücksichtigt werden müssen, bedarf es hierbei aber spezifischer Trigger Tools. UAE, die im ambulanten Bereich auftreten und zu einer stationären Aufnahme führen, sind von besonderer Schwere und mit Leid für die Patienten sowie mit Kosten für das Gesundheits-system verbunden. Ihre Erkennung und subsequente Vermeidung sind demzufolge von be-sonderer Relevanz. Die bereits bestehenden pädiatrischen Tools fokussieren sich ausschließ-lich auf die stationäre Arzneimittelanwendung. Das Ziel dieser Arbeit war daher die Entwick-lung und Validierung eines pädiatrischen Trigger Tools zur Erkennung arzneimittelbedingter stationärer Aufnahmen. Methode Ausgangspunkt war eine umfassende Literaturrecherche in PubMed. Die daraus identifizierten Trigger wurden unter Einbeziehung von pädiatrisch-pharmakologischen Experten weiter kon-solidiert und eine vorläufige Version des Algorithmus gebildet. Nach der retrospektiven Pilotie-rung des Tools an 292 nicht-elektiven Patientenepisoden wurden die Testmerkmale Sensitivi-tät, Spezifität sowie positiver prädiktiver Wert (PPV) bestimmt. Die daraufhin überarbeitete Version wurde im Rahmen des KiDSafe-Projekts an der Kinder- und Jugendklinik Erlangen sowie in elf weiteren deutschen Kinderkliniken zur Erkennung UAE-bedingter Hospitalisierun-gen eingesetzt. Von den Erlangener Daten wurde eine zufällige Stichprobe (n = 1000) gewählt und die Testmerkmale bestimmt. Zusätzlich stellten alle beteiligten Kliniken weitere Episoden und ausgefüllte Algorithmen zur Verfügung. Anhand dieser Daten wurde der Algorithmus in drei Überarbeitungsschritten weiter angepasst und finalisiert. Die finale Version wurde an einer unabhängigen Stichprobe aus vier KiDSafe-Projektkliniken (n = 300) validiert. Ergebnisse Über die Literaturrecherche wurden mehr als 2000 Referenzen identifiziert. Aus diesen Refe-renzen wurden 183 Trigger abgeleitet, die im Verlauf für die vorläufige Algorithmus-Version auf 38 reduziert und den vier Modulen „Allgemein“, „Arzneimittel“, „Symptome“ und „Labor-werte“ zugeordnet wurden. Während der Pilotierung an 292 Patienten lag die Sensitivität bei 0,9546 [0,8930; 1; KI 95 %], die Spezifität bei 0,1653 [0,1191; 0,2116; KI 95 %] und das PPV bei 0,1687 [0,1222; 0,2152; KI 95 %]. Neben kleineren Anpassungen wurde in der Folgever-sion das Arzneimittel-Modul mit dem Modul für Symptome beziehungsweise mit dem für La-borwerte verknüpft. Dadurch wurde im Weiteren ein UAE-Verdacht nur bei gleichzeitiger Trig-ger-Aktivierung innerhalb beider Module erzeugt. Auf Grundlage der 1000 Patientenepisoden und der von den KiDSafe-Kliniken zur Verfügung gestellten Anwendungsdaten wurden in drei Überarbeitungsschritten weitere Anpassungen am Algorithmus vorgenommen, wobei sich die Anzahl seiner Trigger auf 28 reduzierte. Bei der Anwendung in der Validierungs-Stichprobe mit 300 Patientenepisoden zeigte die finale Version schließlich eine Sensitivität von 0,8400 [0,6963; 0,9837; KI 95 %], eine Spezifität von 0,8291 [0,7846; 0,8736; KI 95 %] und ein PPV von 0,3088 [0,1990; 0,4186; KI 95 %]. Diskussion und praktische Implikationen Der in dieser Arbeit entwickelte Algorithmus zeichnet sich durch eine gute Sensitivität und Spezifität aus, die an einer unabhängigen Stichprobe bestätigt wurden und mit bereits etab-lierten Trigger Tools vergleichbar sind. Vor allem der neuartige Ansatz, Module miteinander zu koppeln trägt zur hohen Spezifität des Algorithmus bei. Der Algorithmus muss nun unter Pra-xisbedingungen eingesetzt werden, um finale Aussagen über seine Anwendbarkeit treffen zu können. Perspektivisch soll der entwickelte Algorithmus dazu beitragen, auch ambulante UAE systematisch zu erfassen und zur Meldung zu bringen, woran sich weitere Maßnahmen zur Prävention dieser Ereignisse anschließen können. Auch seine Integration in ein elektronisches Klinik-Informationssystem zur automatisierten Durchsicht der Patientenaufnahmen ist denk-bar.
Antibiotics are the drugs most frequently prescribed for children, and most of them lack patent protection. The aim of this study was to evaluate off-label antibiotic use in three European countries.
Data relating to all patients admitted to the neonatal intensive care units (NICUs) and paediatric wards of the participating centres were collected by the same investigator over a 2-week survey period between February and May 2009. The data included age, date of birth, weight, relevant medical history and diagnosis, together with details of all of the antibiotics prescribed (compound, route of administration, dose, and indication for use).
The study involved 616 children (110 admitted to NICUs: 62 in the UK, 38 in Italy and 10 in Greece; 506 admitted to general paediatric wards: 265 in the UK, 94 in Italy and 147 in Greece). A total of 1,244 antibiotic prescriptions were issued (290 in NICUs and 954 in paediatric wards). The results showed that off-label antibiotic use is very common among European paediatric patients, with generally only slight, but sometimes significant differences between countries. However, this use relates almost exclusively to doses and indications, and rarely to age. The only antibiotics found to be used off-label in an age-related manner in paediatric clinical practice are meropenem for neonates and quinolones or linezolid for older children, which represent priorities for future studies.
European-wide educational programmes are urgently needed to meet the objectives of improving paediatricians' working knowledge of the recommendations surrounding licensed antibiotics-use in children, and of reducing uncontrolled patterns of prescribing.
Children should not be harmed by their participation in clinical trials, therefore should no clinical trials be performed? This is a view that needs to be balanced as clinical trials provide the evidence we need to allow children safe and effective prescribing of medicines. Therefore, is it unethical not to involve this population in research? This review looks at new ethical guidance released to support the recently introduced European legislation for the licensing of medicines.
