Use of antimicrobials in pediatric wards of five Brazilian hospitals.

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.

Translation, transcultural adaptation and validation to Brazilian Portuguese of tools for adverse drug reaction assessment in children.

BACKGROUND: Children are more vulnerable to adverse drug reactions (ADRs) due to complex changes in the body during the growth process and lack specific pharmacoepidemiologic studies. Causality and Avoidability assessment of ADRs are relevant to clinical guidelines development and pharmacovigilance. This study aimed to translate and transcultural adapt two new tools-Liverpool Causality Assessment Tool (LCAT) and the Liverpool Avoidability Assessment Tool (LAAT)-to Brazilian-Portuguese and evaluate the psychometric properties of these tools to analyse ADRs in Brazilian children. METHODS: The validation of the cross-cultural adaptation of tools was obtained by the functional (conceptual, semantic, operational, and measurement) equivalence between the original and translated versions of each instrument. The translated version of LCAT and LAAT was applied to assessing the twenty-six case reports of suspected adverse drug reactions in a Brazilian teaching paediatric hospital. The inter-rater reliability (a pharmacist and a physician) was evaluated using Cronbach's alpha. The exact agreement percentages (%EA) and extreme disagreement (%ED) were computed. Overall Kappa index was calculated with a 95% confidence interval. RESULTS: There was a need to modify some terms translated into Portuguese for semantic and conceptual equivalence. The Cronbach's alpha coefficient values obtained were 0.95 and 0.85, and the weighted Kappa (95% confidence interval) were 0.82 (0.67-0.97) and 0.68 (0.45-0.91) for LCAT and LAAT, respectively. The Brazilian-Portuguese versions of the LCAT and LAAT showed reliable and valid tools for the diagnosis and follow-up of ADRs in children. CONCLUSION: The methodological approach allowed the translation, transcultural adaptation, and validation to Brazilian-Portuguese of two easy and quick to perform tools for causality and avoidability of ADRs in children by a multidisciplinary expert specialist committee, including the authors of original tools. We believe these versions may be applied by professionals (patient safety teams) and researchers in Brazil in groups or by a single reviewer. TRIAL REGISTRATION: This study was evaluated and approved by the Research Ethics Committee (Instituto de Pediatria e Puericultura Martagão Gesteira - Federal University of Rio de Janeiro - Number: 3.264.238.

Contextualizing the COVID-19 pandemic's impact on food security in two small cities in Bangladesh.

The COVID-19 pandemic is an evolving urban crisis. This research paper assesses impacts of the lockdown on food security and associated coping mechanisms in two small cities in Bangladesh (Mongla and Noapara) during March to May 2020. Due to restrictions during the prolonged lockdown, residents (in particular low-income groups) had limited access to livelihood opportunities and experienced significant or complete loss of income. This affected both the quantity and quality of food consumed. Coping strategies reported include curtailing consumption, relying on inexpensive starchy staples, increasing the share of total expenditure allocated to food, taking out loans and accessing relief. The pandemic has exacerbated the precariousness of existing food and nutrition security in these cities, although residents with guaranteed incomes and adequate savings did not suffer significantly during lockdown. While coping strategies and the importance of social capital are similar in small and large cities, food procurement and relationships with local governments show differences.

Adverse drug reactions and off-label and unlicensed medicines in children: a nested case-control study of inpatients in a pediatric hospital.

BACKGROUND: Off-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs. METHODS: A nested case?control study was conducted within a prospective cohort study. Details of all medicines administered were recorded, including information about OLUL status. The odds ratio for OLUL medicines being implicated in a probable or definite ADR was calculated. A multivariate Cox proportional hazards regression model was fitted to the data to assess the influence that OLUL medicine use had on the hazard of an ADR occurring. RESULTS: A total of 10,699 medicine courses were administered to 1,388 patients. The odds ratio (OR) of an OLUL medicine being implicated in an ADR compared with an authorized medicine was 2.25 (95% confidence interval (CI) 1.95 to 2.59). Medicines licensed in children but given to a child below the minimum age or weight had the greatest odds of being implicated in an ADR (19% of courses in this category were implicated, OR 3.54 (95% CI 2.82 to 4.44). Each additional OLUL medicine given significantly increased the hazard of an ADR (hazard ratio (HR) 1.3 95% CI 1.2 to 1.3, P <0.001). Each additional authorized medicine given also significantly increased the hazard (HR 1.2 95% CI 1.2 to 1.3, P <0.001). CONCLUSIONS: OLUL medicines are more likely to be implicated in an ADR than authorized medicines. The number of medicines administered is a risk factor for ADRs highlighting the need to use the lowest number of medicines, at the lowest dose for the shortest period, with continual vigilance by prescribers, in order to reduce the risk of ADRs.

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children - a prospective observational cohort study of 6,601 admissions.

BACKGROUND: Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. METHODS: We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. RESULTS: A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). CONCLUSIONS: ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries.

How are Research for Development Programmes Implementing and Evaluating Equitable Partnerships to Address Power Asymmetries?

The complexity of issues addressed by research for development (R4D) requires collaborations between partners from a range of disciplines and cultural contexts. Power asymmetries within such partnerships may obstruct the fair distribution of resources, responsibilities and benefits across all partners. This paper presents a cross-case analysis of five R4D partnership evaluations, their methods and how they unearthed and addressed power asymmetries. It contributes to the field of R4D partnership evaluations by detailing approaches and methods employed to evaluate these partnerships. Theory-based evaluations deepened understandings of how equitable partnerships contribute to R4D generating impact and centring the relational side of R4D. Participatory approaches that involved all partners in developing and evaluating partnership principles ensured contextually appropriate definitions and a focus on what partners value. Supplementary Information: The online version contains supplementary material available at 10.1057/s41287-023-00578-w.

Finally, centring reflexivity within a learning oriented approach ensured that partnership evaluation findings were used to adapt and improve the way R4D programmes operate. La complexité des enjeux abordés par la recherche pour le développement (R4D) nécessite des collaborations entre des partenaires de disciplines et de contextes culturels variés. Les asymétries de pouvoir au sein d'un tel partenariat peuvent entraver la répartition équitable des ressources, des responsabilités et des avantages entre tous les partenaires. Cet article présente une analyse croisée de cinq évaluations de partenariats R4D, leurs méthodes et la manière dont elles ont mis au jour et traité les asymétries de pouvoir. Cet article contribue au domaine des évaluations de partenariats R4D en décrivant de façon détaillée les approches et les méthodes employées pour évaluer ces partenariats. Les évaluations basées sur la théorie ont permis d'approfondir la compréhension de la manière dont les partenariats équitables contribuent à l'impact de la R4D et à mettre au centre l'aspect relationnel de la R4D. Les approches participatives impliquant tous les partenaires dans l'élaboration et l'évaluation des principes du partenariat ont permis de garantir des définitions adaptées au contexte et de faire en sorte que les évaluations se penchent sur ce qui est jugé important pour tous les partenaires. Enfin, le fait de mettre la réflexivité au cœur de l'analyse dans une approche axée sur l'apprentissage a permis d'utiliser les résultats de l'évaluation du partenariat pour adapter et améliorer le fonctionnement des programmes de R4D.

Adverse Drug Reactions to Anti-infectives in Hospitalized Children: A Multicenter Study in Brazil.

INTRODUCTION: Adverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems. OBJECTIVE: To assess ADRs associated with anti-infective use in Brazilian hospitalized children. METHODS: A prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0-11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included. RESULTS: A total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P < .001), increased length of therapy (P < .015), increased days of therapy (P = .038), and increased number of anti-infectives prescribed per patient (P < .001). CONCLUSION: Almost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient.

Optimal Management of Status Epilepticus in Children in the Emergency Setting: A Review of Recent Advances.

Convulsive status epilepticus (CSE) is the most common neurological emergency in children and the second most common neurological emergency in adults. Mortality is low, but morbidity, including neuro-disability, learning difficulties, and a de-novo epilepsy, may be as high as 22%. The longer the duration of CSE, the more difficult it is to terminate, and the greater the risk of morbidity. Convulsive status epilepticus is usually managed using specific national or local algorithms. The first-line treatment is administered when a tonic-clonic or focal motor clonic seizure has lasted five minutes (impending or premonitory CSE). Second-line treatment is administered when the CSE has persisted after two doses of a first-line treatment (established CSE). Randomised clinical trial (RCT) evidence supports the use of benzodiazepines as a first-line treatment of which the most common are buccal or intra-nasal midazolam, rectal diazepam and intravenous lorazepam. Alternative drugs, for which there are considerably less RCT data, are intra-muscular midazolam and intravenous clonazepam. Up until 2019, phenobarbital and phenytoin (or fosphenytoin) were the preferred second-line treatments but with no good supporting RCT evidence. Robust RCT data are now available which has provided important information on second-line treatments, specifically phenytoin (or fosphenytoin), levetiracetam and sodium valproate. Lacosamide is an alternative second-line treatment but with no supporting RCT evidence. Current evidence indicates that first, buccal or intranasal midazolam or intravenous lorazepam are the most effective and the most patient and carer-friendly first-line anti-seizure medications to treat impending or premonitory CSE and second, that there is no difference in efficacy between levetiracetam, phenytoin (or fosphenytoin) or sodium valproate for the treatment of established CSE. Pragmatically, levetiracetam or sodium valproate are preferred to phenytoin (or fosphenytoin) because of their ease of administration and lack of serious adverse side-effects, including potentially fatal cardiac arrhythmias. Sodium valproate must be used with caution in children aged three and under because of the rare risk of hepatotoxicity and particularly if there is an underlying mitochondrial disorder.

Development and evaluation of an assessment of the age-appropriateness/inappropriateness of formulations used in children.

BACKGROUND: Medicines designed for adults may be inappropriate for use in children in terms of strength, dosage form and/or excipient content. There is currently no standardised method of assessing the age-appropriateness of a medicine for paediatric use. AIM: To develop and test a tool to assess whether a dosage form (formulation) is appropriate for children and estimate the proportion of formulations considered 'inappropriate' in a cohort of hospitalised paediatric patients with a chronic illness. METHOD: A multi-phase study: patient data collection, tool development, case assessments and tool validation. Inpatients aged 0-17 years at two UK paediatric/neonatal hospitals during data collection periods between January 2015 and March 2016. Written informed consent/assent was obtained. Medicines assessed were new or regularly prescribed to inpatients as part of their routine clinical care. All medicine administration episodes recorded were assessed using the Age-appropriate Formulation tool. The tool was developed by a consensus approach, as a one-page flowchart. Independent case assessments were evaluated in 2019. RESULTS: In 427 eligible children; 2,199 medicine administration episodes were recorded. Two assessors reviewed 220 episodes in parallel: percentage exact agreement was found to be 91.7% (99/108) and 93.1% (95/102). In total, 259/2,199 (11.8%) medicine administration episodes involved a dosage form categorised as 'age-inappropriate'. CONCLUSION: A novel tool has been developed and internally validated. The tool can identify which medicines would benefit from development of an improved paediatric formulation. It has shown high inter-rater reliability between users. External validation is needed to further assess the tool's utility in different settings.

Pharmacogenomics and asthma treatment: acceptability to children, families and healthcare professionals.

BACKGROUND: Evidence supporting personalised treatment for asthma based on an individual's genetics is mounting. The views of children and young people (CYP), parents and healthcare professionals (HCPs) about this evolution of clinical care are not known. METHODS: A pilot prospective questionnaire-based study was undertaken of CYP with asthma, their parents and HCPs at a secondary/tertiary children's hospital in the UK. RESULTS: Fifty-nine questionnaires were distributed and 50 returned (response rate 84.7%), comprising 26 CYP (10 were 5-11 years, 11 were 12-15 years and 5 were 16-18 years old), 13 parents and 11 HCPs. For all types of data, personal information was ranked as the 'most important' (n=19, 47.5%) and 'most private' (n=16, 40%), but with considerable variation across groups. Within health data, allergies were rated as 'most important' (n=12, 30.8%), and mental health records the 'most private' (n=21, 53.8%), again with variation across groups. A 'personalised genetic asthma plan' was acceptable to the majority overall (n=40, 80.0%). With regard to sharing CYP's genetic data, 23 (46%) of participants were happy for unconditional sharing between HCPs, and 23 (46%) agreed to sharing solely in relation to the CYP's asthma management. Forty-two (84.0%) of participants felt CYP should be informed about genetic data being shared, and the majority felt this should commence by 12 years of age. CONCLUSION: The use of genetic information to guide management of asthma in CYP is largely acceptable to CYP, parents/guardians and HCPs. However, there are key differences between the opinions of CYP, parents and HCPs.

Creating Acceptable Tablets 3D (CAT 3D): A Feasibility Study to Evaluate the Acceptability of 3D Printed Tablets in Children and Young People.

3D printing (3DP) has been proposed as a novel approach for personalising dosage forms for children and young people (CYP). Owing to its low cost and the lack of need for finishing steps, fused deposing modelling (FDM) 3DP has been heavily researched in solid dosage forms (SDFs) manufacturing. However, the swallowability and overall acceptability of 3D printed dosage forms are yet to be established. This work is the first to evaluate the acceptability of different sized 3D printed placebo SDFs in CYP (aged 4-12 years). All participants had previously participated in a feasibility study (CAT study) that assessed the swallowability and acceptability of different sized GMP manufactured placebo conventional film-coated tablets, and therefore only attempted to swallow one 3D printed tablet. The participants assessed the swallowability, acceptability, mouthfeel, volume of water consumed, and taste of the sample using a 5-point hedonic facial scale on a participant questionnaire. A total of 30 participants were recruited, 87% of whom successfully swallowed the 3D printed tablet that they attempted to take. Attributes of the 3D printed tablets were scored as acceptable by the following percentage of participants-swallowability (80%), mouthfeel/texture (87%), the volume of water consumed (80%), taste (93%), and overall acceptability (83%). Overall, 77% of children reported they would be happy to take the tablet every day if it was a medicine. Participants were also asked which tablets felt better in the mouth-the film-coated tablets or the 3D printed tablets, and the most popular response (43%) was that both were acceptable. This study shows that FDM-based 3D printed SDFs may be a suitable dosage form for children aged 4-12 years. The results from this feasibility study will be used to inform a larger, definitive study looking at the acceptability of 3D printed tablets in children.

Paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT): An e-survey of the experiences of parents and clinicians.

BACKGROUND: Little evidence exists about parental satisfaction and their influence on referral to paediatric Outpatient Parenteral Antimicrobial Therapy (OPAT). AIM: This study aimed to examine the experiences of parents, children and clinicians of OPAT at a large tertiary children's hospital. METHOD: A prospective e-survey, using closed and open questions, of parents (n = 33) of 33 children who had received OPAT (3 children completed a survey), and clinicians (n = 31) involved in OPAT at a tertiary hospital. Data were collected September 2016 to July 2018. RESULTS: Data were analysed using simple descriptive statistics. The results show that OPAT offered benefits (less stress, re-establishment of family life) compared to hospital-based treatment for parents and children, although some were anxious. Clinicians' referral judgements were based on child, home, and clinical factors. Some clinicians found the process of referral complex. CONCLUSION: Most parents and children were satisfied with the OPAT service and preferred the option of home-based treatment as it promoted the child's comfort and recovery and supported family routines.

Exploring Acceptability Drivers of Oral Antibiotics in Children: Findings from an International Observational Study.

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population.

Two classes of functional connectivity in dynamical processes in networks.

The relationship between network structure and dynamics is one of the most extensively investigated problems in the theory of complex systems of recent years. Understanding this relationship is of relevance to a range of disciplines-from neuroscience to geomorphology. A major strategy of investigating this relationship is the quantitative comparison of a representation of network architecture (structural connectivity, SC) with a (network) representation of the dynamics (functional connectivity, FC). Here, we show that one can distinguish two classes of functional connectivity-one based on simultaneous activity (co-activity) of nodes, the other based on sequential activity of nodes. We delineate these two classes in different categories of dynamical processes-excitations, regular and chaotic oscillators-and provide examples for SC/FC correlations of both classes in each of these models. We expand the theoretical view of the SC/FC relationships, with conceptual instances of the SC and the two classes of FC for various application scenarios in geomorphology, ecology, systems biology, neuroscience and socio-ecological systems. Seeing the organisation of dynamical processes in a network either as governed by co-activity or by sequential activity allows us to bring some order in the myriad of observations relating structure and function of complex networks.

A new framework for integrated, holistic, and transparent evaluation of inter-basin water transfer schemes.

Water shortages are forecast to affect 50% of the world's population by 2030, impacting developing nations most acutely. To increase water security there has been a significant increase in Inter-basin Water Transfer (IBWT) schemes, engineering mega-projects that redistribute water from one basin to another. However, the implementation of these schemes is often contested, and evaluation of their complex impacts inadequate, or hidden from full public scrutiny. There is an urgent need to develop more integrated, holistic, and transparent ways of evaluating the multiple interlinking impacts of IBWT schemes of this scale. In this paper, we address this gap by outlining an experimental methodology to evaluate IBWT schemes using a multidisciplinary and transparent methodology which utilises publicly available data. We illustrate the method using a case study from the Inter-Linking Rivers Project in Northern India, comparing the results of the experimental approach against the official analysis of the proposed scheme produced by the State Government of Jharkhand. The results demonstrate that the proposed experimental method allows more detailed evaluation of spatial and temporal variability in water availability and demand, as well as holistic evaluation of the functioning of the proposed scheme under different future scenarios. Based on these results we propose a flexible framework for future evaluation of proposed water transfer schemes which embeds the principles of integrated assessment, transparency, and sound science which can be adapted to other IBWT projects across the world.

The implementation of a Technician Enhanced Administration of Medications [TEAM] model: An evaluative study of impact on working practices in a children's hospital.

BACKGROUND: Children are frequently prescribed unlicensed and off-label medicines meaning dosing and administration of medicines to children is often based on poor quality guidance. In UK hospitals, nursing staff are often responsible for administering medications. Medication Errors [MEs] are problematic for health services, though are poorly reported and therefore difficult to quantify with confidence. In the UK, children's medicines require administration by at least two members of ward staff, known as a 'second check' system, thought to reduce Medication Administration Errors [MAEs]. OBJECTIVES: To assess the impact on working practices of the introduction of a new way of working, using Technician Enhanced Administration of Medications [TEAM] on two specialist wards within a children's' hospital. To evidence any potential impact of a TEAM ward-based pharmacy technician [PhT] on the reporting of MEs. METHODS: A TEAM PhT was employed on two wards within the children's hospital and trained in medicines administration. Firstly, an observational pre-and-post cohort design was used to identify the effect of TEAM on MEs. We analysed the hospital's official reporting system for incidents and 'near misses', as well as the personal incident log of the TEAM PhT. Secondly, after implementation, we interviewed staff about their perceptions of TEAM and its impact on working practices. RESULTS: We affirm MEs are considerably under-reported in hospital settings, but TEAM PhTs can readily identify them. Further, placing TEAM PhTs on wards may create opportunities for inter-professional knowledge exchange and increase nurses' awareness of potential MAEs, although this requires facilitation. CONCLUSIONS: TEAM PhT roles may be beneficial for pharmacy technicians' motivation, job satisfaction, and career development. Hospitals will need to consider the balance between resources invested in TEAM PhTs and the level of impact on reporting MEs. Health economic analyses could provide evidence to fully endorse integration of TEAM PhTs for all hospital settings.

Being 'at-home' on outpatient parenteral antimicrobial therapy (OPAT): a qualitative study of parents' experiences of paediatric OPAT.

OBJECTIVE: To better understand the factors that facilitate and hinder a positive experience of paediatric outpatient parenteral antimicrobial therapy (OPAT). DESIGN: Qualitative study using semistructured interviews. SETTING: A dedicated paediatric consultant-led hospital-based, outreach OPAT service in England. PARTICIPANTS: Participants were primarily parents of children who had received OPAT; one child participated. METHODS: Children and parents of children who received OPAT and who had participated in the survey phase of the larger study were invited to be interviewed. RESULTS: 12 parents (10 mothers and 2 fathers) of 10 children participated; one child (aged 15 years). Data analysis resulted in one meta-theme, 'At-homeness' with OPAT, this reflected the overall sense of home being a place in which the children and their parents could be where they wanted to be. Four key themes were identified that reflect the ways in which parents and children experienced being at-home on OPAT: 'Comfort, security, freedom, and control'; 'Faith, trust and confidence'; 'Explanations and communication' and 'Concerns, restrictions and inconveniences'. CONCLUSIONS: Despite feeling anxious at times, parents reported that they and their children generally had a positive experience of OPAT; being at-home brought many benefits compared with in-patient care. Recommendations arising from the study include a 'whole-system' approach to discharge home that includes support related to return to school/nursery, reduction in disruptions to home-based routines, more clarity on choice and preparation for managing potential anxiety, better consideration of dose timing and enhanced preparation and information.

Serious Adverse Drug Reactions and Safety Signals in Children: A Nationwide Database Study.

Children are more exposed to inappropriate medicine use and its consequent harms. Spontaneous reporting of suspected Serious Adverse Drug Reactions (SADR) increases knowledge and prevention of pharmacotherapy risk. Disproportionality measures are useful to quantify unexpected safety issues associated with a given drug-event pair (signals of disproportionality). This cross-sectional study aimed to assess SADR reporting and safety signals for Brazilian children from 0-12 years old, notified between January 2008 and December 2013 from the Brazilian Surveillance Agency (Notivisa). Information from serious reports (gender and age of the patient, event description, suspected drug) was included. Disproportionality analysis based on Reporting Odds Ratios with a confidence interval of 95% was conducted to identify possible signals of disproportionate reporting (SDR). Almost 30% of 1,977 suspected SADR was related to babies (0-1-year-old). 69% of reports happened with intravenous dosage forms, and 35% of suspected SADR involved off label use according to age. Laronidase, miglustat, imipenem/cilastatin, and clofarabine were involved in six or more suspected deaths among 75 deaths reported. There were 107 SDRs, of which 16 events (15%) were not described in the product labels. There was a relatively higher number of SADRs in Brazilian children compared with studies from other countries. SDRs found, (especially drug-event pairs 'imipenen/cilastatin-pneumonia' and 'laronidase-respiratory insufficiency') should be investigated more. The reports of SADR with IV dosage forms and OL drug use suggest the need for drug research and the use of better dosage forms for children in Brazil.

Can children swallow tablets? Outcome data from a feasibility study to assess the acceptability of different-sized placebo tablets in children (creating acceptable tablets (CAT)).

OBJECTIVE: Feasibility study to investigate the acceptability of different-sized placebo tablets in children aged 4-12 years. DESIGN AND SETTING: Clinical Research Facilities, inpatient wards and outpatient clinics within a Regional Paediatric Hospital and/or District General Hospital. Healthy children and National Health Service (NHS) patients were asked to swallow three placebo tablets: 6 mm, 8 mm and 10 mm, smallest to largest. The researcher observed children's facial expressions and behaviours on swallowing and measured the volume of water consumed. Participants completed a questionnaire about the overall acceptability; including swallowability, taste and volume of water consumed. For analysis, participants were stratified by age: 4-8 years and 9-12 years. RESULTS: The feasibility study led to an estimated recruitment rate of 0.8% for NHS inpatients and 211 healthy children over a 1-year period. In total, 55 participants were recruited, 30 to the younger group, of which 77% had never taken a tablet before. 84% of the 25 older children had previously taken a tablet. All participants attempted to swallow the smallest sized tablet. The children aged 4-8 years found the larger tablets easier to swallow, however the older children found little difference between the tablet sizes. The younger children required more water to swallow each tablet size compared with the older children where an increasing volume of water was consumed as tablet size increased. Taste was rated highly for both age groups. The 8 mm tablets were deemed the most acceptable tablet size by all participants. CONCLUSION: Tablets are potentially an acceptable formulation for children aged 4-12 years. Most children aged 4-8 years who attempted to swallow tablets successfully did so. Recruitment of NHS inpatients to medicine acceptability studies is challenging, however, recruitment of children of staff proved an effective strategy. Valuable lessons have been learnt from this feasibility study which will inform the design of a larger definitive trial.