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Author(s): Thomas J. Hwang 1,2,3, Paolo A. Tomasi 4, Florence T. Bourgeois 1,2,5,* Introduction Historically, information on the safety, efficacy, and appropriate use of new medicines in children has been [...], Background Few medicines have been approved for children, leading to rates of off-label prescribing reported to be as high as 90%. In 2007, the European Union adopted the Paediatric Regulation, which mandates that pharmaceutical companies conduct paediatric studies for all new medicines, unless granted a waiver. We aimed to evaluate the availability of paediatric trial results from studies required under the Paediatric Regulation for new medicines authorised in the EU. Methods and findings The European Medicines Agency (EMA) public database of paediatric investigation plans was searched for new medicines centrally authorised in the EU between 1 January 2010 and 31 December 2014 with at least 1 required paediatric study. For our study cohort of paediatric clinical trials required for these medicines, we used internal EMA databases and publicly available trial registries to determine changes to the planned completion date or study design, rates of trial completion, time to trial completion, and results reporting (peer-reviewed publication or posting on trial registry). Cox proportional hazards regression models were constructed to examine factors associated with study completion. A total of 326 paediatric clinical trials were required for 122 novel medicines authorised by the EMA between 2010 and 2014. In all, 76% (247/326) of paediatric studies were not planned to be completed until after the initial marketing authorisation. The planned completion dates for 50% (162/326) were further postponed by a median of 2.2 years. Overall, 38% (124/326) of paediatric studies were completed as of 30 November 2017. The rate of trial completion for paediatric studies planned to be completed after initial marketing authorisation was 23% (56/247), versus 86% (68/79) for trials planned to be completed before authorisation (adjusted hazard ratio 0.11; 95% CI 0.06-0.19). Among completed studies, the results were reported in a public registry or in the peer-reviewed literature for 85% (105/124) at a median of 1.1 years after study completion, and 60% (74/124) were published in a peer-reviewed journal. Limitations of this study include the potential lack of generalisability to medicines not authorised by the EMA and the possibility for more of these trials to be completed or published in the future. Conclusions The completion of many paediatric studies required under the Paediatric Regulation has been delayed. Paediatric studies planned to be completed after marketing authorisation were associated with a lower likelihood of eventual completion, highlighting the need to examine the implementation of current policies in ensuring timely availability of important paediatric information.

Background. Rapid antigen detection testing (RADT) is often performed for diagnosis of group A J3-hemolytic streptococcal (GABHS) pharyngitis among children. Among adults, the sensitivity of this test varies on the basis of disease severity (spectrum bias). A similar phenomenon may occur when this test is used in a pediatric population, which may affect the need for culture confirmation of all negative RADT results. Objectives. To assess the performance of a clinical scoring system and to determine whether RADT spectrum bias is present among children who are evaluated for GABHS pharyngitis. Methods. Laboratory and clinical records for a consecutive series of pediatric patients who underwent RADT at the Marshfield Clinic between January 2002 and March 2002 were reviewed retrospectively. Patients were stratified according to the number of clinical features present by using modified Centor criteria, ie, history of fever, absence of cough, presence of pharyngeal exudates, and cervical lymphadenopathy. The sensitivity of the RADT was defined as the number of patients with positive RADT results divided by the number of patients with either positive RADT results or negative RADT results but positive throat culture results. Results. RADT results were positive for 117 of 561 children (21%), and culture results were positive for 35 of 444 children (8%) with negative RADT results. The overall prevalence of GABHS pharyngitis was 27% (95% confidence interval: 23-31%). The prevalence of GABHS pharyngitis was 18% among patients with 0 Centor criteria, 16% among those with 1 criterion, 32% among those with 2 criteria, and 50% among those with 3 or 4 criteria. Spectrum bias was present, inasmuch as RADT sensitivity increased with Centor scores, ie, 47% sensitivity among children with 0 Centor criteria, 65% among those with 1 criterion, 82% among those with 2 criteria, and 90% among those with 3 or 4 criteria. Conclusions. The sensitivity of RADT for GABHS pharyngitis is not a fixed value but varies with the severity of disease. However, even among pediatric patients with [greater than or equal to] 3 Centor criteria for GABHS pharyngitis, the sensitivity of RADT is still too low to support the use of RADT without culture confirmation of negative results. Pediatrics 2004;114:182-186; spectrum bias, group A streptococci, rapid antigen detection. ABBREVIATIONS. GABHS, group A [beta]-hemolytic streptococcal; RADT, rapid antigen detection testing; CI, confidence interval., Group A [beta]-hemolytic streptococcal (GABHS) pharyngitis is an important cause of childhood morbidity and the cause of acute rheumatic fever. (1) According to national guidelines, the diagnosis of GABHS pharyngitis [...]

Background. This study reports the epidemiologic features, survival rates, and neurologic outcomes of the largest population-based series of pediatric out-of-hospital cardiopulmonary arrest patients with prospectively collected data. Methods. Secondary analysis of data from a prospective, interventional trial of out-of-hospital pediatric airway management conducted from 1994 to 1997 (Gausche M, Lewis RJ, Stratton SJ, et al. JAMA. 2000;283:783-790). Consecutive out-of-hospital patients from 2 large urban counties in California Results. In 599 patients, 601 events were studied (54% were 3 doses of epinephrine or were resuscitated for >31 minutes in the emergency department. Conclusions. The 8.6% survival rate after out-of-hospital pediatric cardiopulmonary arrest is poor. Administration of >3 doses of epinephrine or prolonged resuscitation is futile. Pediatrics 2004;114:157-164; cardiopulmonary arrest, cardiopulmonary resuscitation, out-of-hospital, prehospital, pediatric. ABBREVIATIONS. EMS, emergency medical services; BMV, bag-mask ventilation; CPR, cardiopulmonary resuscitation; ED, emergency department; ROSC, return of spontaneous circulation; PCPC, Pediatric Cerebral Performance Category; PEA, pulseless electrical activity; IQR, interquartile range; SIDS, sudden infant death syndrome; VF, ventricular fibrillation; VT, ventricular tachycardia., Patient outcomes after pediatric cardiopulmonary arrest are dismal and have not improved over the last 3 decades. (1) Research to improve prevention and therapy and to optimize emergency medical services [...]

Objectives. Acute otitis media (OM) is the most common indication for the use of antibiotics among children. Otoscopy alone is an imprecise method for the diagnosis of OM, which may lead to inappropriate antibiotic use. We sought to determine whether tympanometry, as an adjunct to otoscopy, would significantly change physician prescribing behavior and whether physicians overprescribe antibiotics for OM, using independently graded tympanometry results as a standard. Methods. A randomized, clinical trial was conducted among children 6 to 35 months of age who presented to a pediatric emergency department with either fever or upper respiratory infection symptoms. Children were randomized into 2 groups, in which the attending physician evaluated tympanometry results (Tymp Aware) or the attending physician was blinded to the tympanometry findings (Tymp Unaware). Tympanometry curves were graded independently by using a modified version of the Jerger scale. Results. Of the 698 patients enrolled, tympanometry was performed successfully for 99.3%. Antibiotics were prescribed for OM for 27.9% of all patients. No statistically significant difference in antibiotic prescription rates for OM between the Tymp Aware group (28.8%) and the Tymp Unaware group (26.8%) was found. Of all patients for whom antibiotics were prescribed for OM, 14% had normal curves for both ears and 40% had some tympanographic movement bilaterally. Conclusions. Tympanometry did not seem to change diagnoses or prescribing behavior in the group of physicians studied. Antibiotics were commonly prescribed for presumed OM in the absence of effusions documented with tympanometry. Pediatrics 2004;114:177-181; otitis media, tympanometry, antibiotic, antibiotic resistance, randomized trial design. ABBREVIATIONS, OM, otitis media; PEM, pediatric emergency medicine., An epidemic of microbial resistance is occurring in the United States, attributable in large part to overprescription of antibiotics. (1,2) Although most upper respiratory infections are caused by viral agents, [...]

Objectives. To determine whether the commonly used over-the-counter medications dextromethorphan and diphenhydramine are superior to placebo for the treatment of nocturnal cough and sleep difficulty associated with upper respiratory infections and to determine whether parents have improved sleep quality when their children receive the medications when compared with placebo. Methods. Parents of 100 children with upper respiratory infections were questioned to assess the frequency, severity, and bothersome nature of the nocturnal cough. Their answers were recorded on 2 consecutive days, initially on the day of presentation, when no medication had been given the previous evening, and then again on the subsequent day, when either medication or placebo was given before bedtime. Sleep quality for both the child and the parent were also assessed for both nights. Results. For the entire cohort, all outcomes were significantly improved on the second night of the study when either medication or placebo was given. However, neither diphenhydramine nor dextromethorphan produced a superior benefit when compared with placebo for any of the outcomes studied. Insomnia was reported more frequently in those who were given dextromethorphan, and drowsiness was reported more commonly in those who were given diphenhydramine. Conclusions. Diphenhydramine and dextromethorphan are not superior to placebo in providing nocturnal symptom relief for children with cough and sleep difficulty as a result of an upper respiratory infection. Furthermore, the medications given to children do not result in improved quality of sleep for their parents when compared with placebo. Each clinician should consider these findings, the potential for adverse effects, and the individual and cumulative costs of the drugs before recommending them to families. Pediatrics 2004;114:e85-e90. URL: http://www.pediatrics.org/cgi/content/full/114/1/ e85; cough, upper respiratory infection, dextromethorphan, diphenhydramine, placebo.