Age within schoolyear and attention-deficit hyperactivity disorder in Scotland and Wales.

BACKGROUND: Previous studies suggest an association between age within schoolyear and attention-deficit hyperactivity disorder (ADHD). Scotland and Wales have different school entry cut-off dates (six months apart) and policies on holding back children. We aim to investigate the association between relative age and treated attention deficit hyperactivity disorder (ADHD) in two countries, accounting for held-back children. METHODS: Routine education and health records of 1,063,256 primary and secondary schoolchildren in Scotland (2009-2013) and Wales (2009-2016) were linked. Logistic regression was used to examine the relationships between age within schoolyear and treated ADHD, adjusting for child, maternity and obstetric confounders. RESULTS: Amongst children in their expected school year, 8,721 (0.87%) had treated ADHD (Scotland 0.84%; Wales 0.96%). In Wales, ADHD increased with decreasing age (youngest quartile, adjusted OR 1.32, 95% CI 1.19-1.46) but, in Scotland, it did not differ between the youngest and oldest quartiles. Including held-back children in analysis of their expected year, the overall prevalence of treated ADHD was 0.93%, and increased across age quartiles in both countries. More children were held back in Scotland (57,979; 7.66%) than Wales (2,401; 0.78%). Held-back children were more likely to have treated ADHD (Scotland OR 2.18, 95% CI 2.01-2.36; Wales OR 1.70, 95% CI 1.21-2.31) and 81.18% of held-back children would have been in the youngest quartile of their expected year. CONCLUSIONS: Children younger within schoolyear are more likely to be treated for ADHD, suggesting immaturity may influence diagnosis. However, these children are more likely to be held back in countries that permit flexibility, attenuating the relative age effect.

Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.

BACKGROUND: Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders. METHODS AND FINDINGS: Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care. CONCLUSIONS: Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.

Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.

BACKGROUND: Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (≥2 conditions) among Scottish schoolchildren and their educational outcomes compared to peers. METHODS AND FINDINGS: We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (≥2 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, ≥2) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications. CONCLUSIONS: Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.

Views and experiences of decision-makers on organisational safety culture and medication errors.

BACKGROUND: In 2017, the World Health Organization published "Medication Without Harm, WHO Global Patient Safety Challenge," to reduce patient harm caused by unsafe medication use practices. While the five objectives emphasise the need to create a framework for action, engaging key stakeholders and others, most published research has focused on the perspectives of health professionals. The aim was to explore the views and experiences of decision-makers in Qatar on organisational safety culture, medication errors and error reporting. METHOD: Qualitative, semi-structured interviews were conducted with healthcare decision-makers (policy-makers, professional leaders and managers, lead educators and trainers) in Qatar. Participants were recruited via purposive and snowball sampling, continued to the point of data saturation. The interview schedule focused on: error causation and error prevention; engendering a safety culture; and initiatives to encourage error reporting. Interviews were digitally recorded, transcribed and independently analysed by two researchers using the Framework Approach. RESULTS: From the 21 interviews conducted, key themes were the need to: promote trust within the organisation through articulating a fair blame culture; eliminate management, professional and cultural hierarchies; focus on team building, open communication and feedback; promote professional development; and scale-up successful initiatives. There was recognition that the current medication error reporting processes and systems were suboptimal, with suggested enhancements in themes of promoting a fair blame culture and open communication. CONCLUSION: These positive and negative aspects of organisational culture can inform the development of theory-based interventions to promote patient safety. Central to these will be the further development and sustainment of a "fair" blame culture in Qatar and beyond.

Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children.

BACKGROUND: The global prevalence of childhood asthma is increasing. The condition impacts physical and psychosocial morbidity; therefore, wide-ranging effects on health and education outcomes are plausible. METHODS: Linkage of eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions and unemployment, provided data on 683 716 children attending Scottish schools between 2009 and 2013. We compared schoolchildren on medication for asthma with peers, adjusting for sociodemographic, maternity and comorbidity confounders, and explored effect modifiers and mediators. RESULTS: The 45 900 (6.0%) children treated for asthma had an increased risk of hospitalisation, particularly within the first year of treatment (incidence rate ratio 1.98, 95% CI 1.93-2.04), and increased mortality (HR 1.77, 95% CI 1.30-2.40). They were more likely to have special educational need for mental (OR 1.76, 95% CI 1.49-2.08) and physical (OR 2.76, 95% CI 2.57-2.95) health reasons, and performed worse in school exams (OR 1.11, 95% CI 1.06-1.16). Higher absenteeism (incidence rate ratio 1.25, 95% CI 1.24-1.26) partially explained their poorer attainment. CONCLUSIONS: Children with treated asthma have poorer education and health outcomes than their peers. Educational interventions that mitigate the adverse effects of absenteeism should be considered.

Educational and health outcomes of children and adolescents receiving antiepileptic medication: Scotland-wide record linkage study of 766 244 schoolchildren.

BACKGROUND: Childhood epilepsy can adversely affect education and employment in addition to health. Previous studies are small or highly selective producing conflicting results. This retrospective cohort study aims to compare educational and health outcomes of children receiving antiepileptic medication versus peers. METHODS: Record linkage of Scotland-wide databases covering dispensed prescriptions, acute and psychiatric hospitalisations, maternity records, deaths, annual pupil census, school absences/exclusions, special educational needs, school examinations, and (un)employment provided data on 766,244 children attending Scottish schools between 2009 and 2013. Outcomes were adjusted for sociodemographic and maternity confounders and comorbid conditions. RESULTS: Compared with peers, children on antiepileptic medication were more likely to experience school absence (Incidence Rate Ratio [IRR] 1.43, 95% CI: 1.38, 1.48), special educational needs (Odds ratio [OR] 9.60, 95% CI: 9.02, 10.23), achieve the lowest level of attainment (OR 3.43, 95% CI: 2.74, 4.29) be unemployed (OR 1.82, 95% CI: 1.60, 2.07), be admitted to hospital (Hazard Ratio [HR] 3.56, 95% CI: 3.42, 3.70), and die (HR 22.02, 95% CI: 17.00, 28.53). Absenteeism partly explained poorer attainment and higher unemployment. Girls and younger children on antiepileptic medication had higher risk of poor outcomes. CONCLUSIONS: Children on antiepileptic medication fare worse than peers across educational and health outcomes. In order to reduce school absenteeism and mitigate its effects, children with epilepsy should receive integrated care from a multidisciplinary team that spans education and healthcare.

Hospital readmissions, mortality and potentially inappropriate prescribing: a retrospective study of older adults discharged from hospital.

AIMS: Applying version 2 of the STOPP/START criteria to discharge prescriptions of older adults discharged from a general medical unit, the aim of this study is to assess potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) and their association with hospital readmission and mortality. METHODS: Discharge medications, co-morbidities and patient demographics were recorded over an 8-month period for consecutive emergency admissions of patients aged ≥65 years. PIMs and PPOs were identified using version 2 of the STOPP/START criteria. Multivariate analysis for association of PIMs and PPOs with re-admissions and mortality during the follow-up period were assessed using binary logistic regression. RESULTS: Data for 259 patients with a mean age of 77 (65-99, 51% female) were analysed. At discharge, the mean number of co-morbidities and medications per patient were 5.4 (SD: 2.1 range: 0-14) and 9.3 (SD: 4.0 range: 1-31) respectively. During the follow-up period (mean 41.5 months, SD: 2.0 range: 38-46 months), 50.2% of patients had died and the median number of readmissions was two (IQR: 1-4 range: 0-33). Prescription of more than five medications was significantly associated with PIMs and PPOs (OR: 2.75, 95% CI: 1.34-5.62 and OR 3.20, 95% CI: 1.57-6.54 respectively). Presence of a PIM was associated with three or more readmissions (OR: 2.43 95% CI: 1.19-4.98) and PPOs with mortality (OR: 1.88, 95% CI: 1.09-3.27). CONCLUSIONS: Using version 2 of the STOPP/START criteria, the presence of PIMs and/or PPOs in older adults discharged from hospital is significantly associated with repeated hospital admissions and mortality respectively.

The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis.

BACKGROUND: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg. L-1 is described in adults. AIMS: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules. METHODS: Pooled intravenous ketorolac (0.5 mg. kg-1 ) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person. RESULTS: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L. h-1. 70 kg-1 and intercompartment clearance was 4.43 (CV 95.6%) L. h-1. 70 kg-1 . Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L. 70 kg-1 and V2 5.53 (CV 47.6%) L. 70 kg-1 . CONCLUSION: Clearance, expressed as L. h-1. kg-1 , decreased with age from infancy. A dosing regimen of 0.5 mg. kg-1 every 6 hours maintains a trough concentration larger than 0.37 mg. L-1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.

Multicompartment compliance aids in the community: the prevalence of potentially inappropriate medications.

AIMS: To assess the prevalence of potentially inappropriate medications (PIMs) use in a population of community-based multicompartment compliance aid (MCA) users in north-east Scotland. METHODS: Data for MCAs dispensed by 48 of the 50 community pharmacies in Aberdeen City between 1st June to 31st October 2014, together with concurrently prescribed medications, patient demographics and Carstairs index of social deprivation were recorded. Drug-specific quality indicators for PIMs from the Swedish National Board of Health and Welfare were applied and bivariate logistic regression analysis used to assess for associations with demographic variables. RESULTS: The median age was 82 years (range 12-105 years, 59% female). A total of 1977 PIMs were identified affecting 57.8% of patients. A quarter of patients were prescribed ≥10 medications and 43% had a prescription containing at least one clinically significant drug-drug interaction (DDI). Ten drug groups accounted for 76% of all DDIs. A significant increase in the risk for at least one PIM was associated with female sex (for all indicators of PIM use), age <80 years (three or more psychotropic medicines [OR 5.88, 2.96-11.70, P < 0.001]) and lower socioeconomic status (prescription of ≥10 medications [OR: 1.43, 95% CI: 1.16-1.78], prescription of a long-acting benzodiazepine [OR: 1.84, CI: 1.14-2.98]). CONCLUSIONS: MCA use is associated with a significant incidence of PIMs particularly affecting those younger than 80 years and those living in deprived areas. Our findings indicate the need for a more aggressive multidisciplinary approach to the review of the medications prescribed to MCA users.

Pregnancy, prescription medicines and the potential risk of herb-drug interactions: a cross-sectional survey.

BACKGROUND: Pregnant women are routinely prescribed medicines while self-medicating with herbal natural products to treat predominantly pregnancy related conditions. The aim of this study was to assess the potential for herb-drug interactions (HDIs) in pregnant women and to explore possible herb-drug interactions and their potential clinical significance. METHODS: A cross-sectional survey of women during early pregnancy or immediately postpartum in North-East Scotland. Outcome measures included; Prescription medicines use excluding vitamins and potential HDIs assessed using Natural Medicines Comprehensive Database. RESULTS: The survey was completed by 889 respondents (73% response rate). 45.3% (403) reported the use of at least one prescription medicine, excluding vitamins. Of those taking prescription medicines, 44.9% (181) also reported concurrent use of at least one HNP (Range 1-12). A total of 91 different prescription medicines were reported by respondents using HNPs. Of those taking prescription medicines, 44.9% (181) also reported concurrent use of at least one HNP (Range 1-12). Thirty-four herb-drug interactions were identified in 23 (12.7%) women with the potential to increase the risk of postpartum haemorrhage, alter maternal haemodynamics, and enhance maternal/fetal CNS depression. Almost all were rated as moderate (93.9%), one as a potentially major (ginger and nifedipine) and only one minor (ondansetron and chamomile). CONCLUSION: Almost half of pregnant women in this study were prescribed medicines excluding vitamins and minerals and almost half of these used HNPs. Potential moderate to severe HDIs were identified in an eighth of the study cohort. Healthcare professionals should be aware that the concurrent use of HNPs and prescription medicines during pregnancy is common and carries potential risks.

Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies.

BACKGROUND: Ketorolac, a potent nonsteroidal anti-inflammatory drug used for pain control in children, exists as a racemate of inactive R (+) and active S (-) enantiomers. AIM: To develop a microsampling assay for the enantioselective analysis of ketorolac in children. METHODS: Ketorolac enantiomers were extracted from 50 µl of plasma by liquid­liquid extraction and separated on a ChiralPak AD-RH. Detection was by a TSQ quantum triple quadrupole mass spectrometer with an electrospray ionisation source operating in a positive ion mode. Five children (age 13.8 (1.6) years, weight 52.7 (7.2) kg), were administered intravenous ketorolac 0.5mg/kg (maximum 10mg) and blood samples were taken at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h post administration. CL, VD and t1/2 were calculated based on non-compartmental methods. RESULTS: The standard curves for R (+) and S (-) ketorolac were linear in the range 0­2000 ng/ml. The LLOQs of the method were 0.15 ng on column and 0.31 ng on column for R (+) and S (-) ketorolac, respectively. The median (range) VD and CL of R (+) and S (-) ketorolac were 0.12 l/kg (0.07­0.17), 0.017 l/h/kg (0.12­0.29) and 0.17 (0.09­0.31) l/kg, 0.049 (0.02­0.1) l/h/kg, p = 0.043), respectively. The median (range) elimination half-life (t1/2) of the R (+) and S (-) ketorolac was 5.0 h (2.5­5.8) and 3.1 h (1.8­4.4), p = 0.043), respectively. CONCLUSION: The development of a simple, rapid and reliable ketorolac assay suitable for paediatric PK studies is reported.

Paracetamol prescribing in primary care: too little and too much?

AIMS: To assess the level of paracetamol off label prescribing in the community and the potential for paracetamol under or overdosing. METHODS: The Scottish Practice Team Information (PTI) database containing prescribing data for approximately 35,839 children aged (0-12 years) was analysed for paracetamol prescriptions for the year 2006. Off label prescribing was defined as prescribing outside the BNFc age and dose recommendations. RESULTS: Two thousand seven hundred and sixty-one children aged 0-12 years were issued with 4423 prescriptions for paracetamol. (1446 males). Children 1-5 years (1329, 42.2%) accounted for 48.9% (2164) of all paracetamol prescriptions. Eighteen per cent (793) of individual prescriptions were off label and after accounting for repeat prescriptions 625 (22.75%) individuals were exposed to off label prescriptions. A further 15% (668) of prescriptions contained insufficient dosage data to determine their status, 13.3% (368) being underdosed and 4.4% (121) overdosed at least once during the study year. In total 11.3% (502) of all prescriptions were classified as underdose, 2.9% (127) as overdose and 15% (667) had no dosage instructions. Age was significantly related to non recommended dosage (χ(2) test, P < 0.001). Children 1-3 months old were at highest risk of being overdosed; 27% of prescriptions recommended actual or potential overdosage and 25% (354) of children aged 6-12 years were prescribed an actual or potential underdose. Overall 57.2% of all prescriptions failed to comply with current BNFc recommendations. CONCLUSION: Paracetamol off label prescribing is common in primary care, with relatively high levels of potential overdosing in the youngest children and potential underdosing in the oldest children.

Using primary care prescribing databases for pharmacovigilance.

AIMS: In the UK, adverse drug reactions (ADRs) are responsible for over 6.5% of all hospital admissions, representing a significant morbidity and cost burden to the health service. We aimed to develop an ADR monitoring system capable of identifying the reasons for patient discontinuation of drug therapy within 6 months of the index prescription. METHODS: Patients first prescribed amlodipine between 1 March 2004 and 28 February 2007 who discontinued their amlodipine medication within 6 months of the index prescription were identified from the practice team information (PTI) database. Once identified, reasons for amlodipine discontinuation were assessed by an electronic database search using relevant Readcodes and key words and by a direct approach to the primary care medical records. RESULTS: The PTI database identified 995 patients [61.4% females, mean age 65.9 years (SD 12.4 years)] who discontinued amlodipine within 6 months of an index prescription. An electronic search of the database, using Readcodes, identified that 19.4% (193) of patients who discontinued their medication had an ADR recorded in the database. Six (20%) of 30 participating primary care practices, contributing to the PTI database, agreed to be approached directly and supply the reasons for discontinuation for the 51 patients identified as having discontinued amlodipine in their practices. Completed data were returned for all 51 patients, 98% of whom discontinued amlodipine due to an ADR or adverse drug event. CONCLUSIONS: The results of this study confirm that primary care prescribing databases can be easily used to identify the frequency and nature of ADRs occurring in an ADR-enriched population identified through medication discontinuation.

Congenital defects and early childhood outcomes following in-utero exposure to antihypertensive medication.

BACKGROUND: Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in-utero exposure to antihypertensive treatment is conflicting with many studies suffering from significant methodological issues. METHOD: We conducted a retrospective cohort study using linked routinely collected healthcare records for 268 711 children born 2010-2014 in Scotland to assess outcomes following in-utero exposure to antihypertensive medication. RESULTS: We identified a cohort of 265 488 eligible mother-child pairs born over the study period; of which, 2433 were exposed in utero to antihypertensive medication, 4391 exposed to treated late-onset hypertension and 6066 exposed to untreated hypertension during pregnancy. In-utero antihypertensive exposure was associated with an increased risk of circulatory defects (aOR 2.29; 99% CI 1.14-4.59) compared with normal controls and the untreated hypertensive group. We report no increased odds of any developmental outcomes at 2.5 years of age following exposure to antihypertensive medication during pregnancy, untreated hypertension or late-onset hypertension. CONCLUSION: Although circulatory defects may be associated with antihypertensive medication exposure during pregnancy, the mechanisms underlying this process are unclear.

Can finger-prick sampling replace venous sampling to determine the pharmacokinetic profile of oral paracetamol?

UNLABELLED: WHAT IS ALREADY KNOWN ABOUT THE SUBJECT: Finger-prick blood samples are increasingly used for the clinical and biomedical measurement of drugs and endogenous substance concentration. The use of different sampling sites can give rise to different drug concentration measurements. WHAT THIS STUDY ADDS: During the absorption phase, the paracetamol concentration in finger-prick blood samples is significantly greater than that in venous blood samples, following oral administration. Finger-prick and venous blood samples will result in equivalent pharmacokinetic parameters of oral paracetamol only after distribution equilibrium is attained. The drive to increase the availability of paediatric pharmacokinetic data with minimum blood loss has led to the development of micro-sampling techniques. However studies have suggested that pharmacokinetic data from venous or capillary blood samples may not be directly comparable. AIM: The aim of this study was to determine whether paracetamol demonstrates concentration differences between finger-prick and venous blood samples. METHODS: Paired finger-prick and venous blood samples were taken at 0, 15, 30 and 60 min following 1 g oral paracetamol, from 12 male adult subjects. Paracetamol concentration was determined using HPLC and UV detection with a LLOQ of 2200 pg on column. Intra-assay coefficient of variation for paracetamol at the LLOQ was 3%. RESULTS: At 15, 30, and 60 min post dose the median finger-prick paracetamol concentration was 349%, 72%, and 9.3% greater than the equivalent venous concentrations, respectively. Regression analysis confirmed a significant relationship between finger-prick and venous paracetamol concentrations at 15 min (r(2) = 0.81, P = 0.006), at 30 min (r(2) = 0.82, P < 0.0001) and at 60 min (r(2) = 0.87, P < 0.0001) post dose. The regression equation for venous and finger-prick blood concentrations at 15, 30 and 60 min post dose were Venous(15) = Finger(15) - 3.4, Venous(30) = Finger(30) - 3.4 and Venous(60) = 0.68 Finger(60) + 3.06, respectively. CONCLUSIONS: Paracetamol demonstrates an arteriovenous difference in concentration, and the use of finger-prick samples may give rise to results which differ from those obtained with traditional venous sampling especially during the first 1 h following drug ingestion.

Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.

BACKGROUND: To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers. METHODS: This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013. RESULTS: After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions. CONCLUSIONS: Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.

In Utero Antihypertensive Medication Exposure and Neonatal Outcomes: A Data Linkage Cohort Study.

Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in utero exposure to antihypertensive treatment is conflicting, with many studies suffering from significant methodological issues, such as inappropriate study design, small sample sizes, and no untreated control group. We conducted a retrospective cohort study using linked routinely collected healthcare records for 268 711 children born 2010-2014 in Scotland to assess outcomes following in utero exposure to antihypertensive medication. We identified a cohort of 265 488 eligible children born over the study period; of which, 2350 were exposed to in utero antihypertensive medication, 4391 exposed to treated late-onset hypertension, and 7971 exposed to untreated hypertension during pregnancy. Untreated hypertension was associated with increased risk of preterm birth (adjusted risk ratio [aRR], 1.15 [99% CI, 1.01-1.30]), low birth weight (aRR, 2.01 [99% CI, 1.72-2.36]) and being small for gestational age (aRR, 1.50 [99% CI, 1.35-1.66]), while in utero antihypertensive exposure was also associated with preterm birth (aRR, 3.12 [99% CI, 2.68-3.64]), low birth weight (aRR, 2.23 [99% CI, 1.79-2.78]), and being small for gestational age (aRR, 2.13 [99% CI, 1.81-2.52]). Late-onset hypertension was also associated with preterm birth (aRR, 2.21 [99% CI, 1.86-2.62]), low birth weight (aRR, 2.06 [99% CI, 1.74-2.43]), and being small for gestational age (aRR, 1.90 [99% CI, 1.68-2.16]). Our results suggest that hypertension is a key risk factor for low birth weight and preterm birth. Although preterm birth may be associated with antihypertensive medication exposure during pregnancy, these associations may reflect increasing hypertension severity necessitating treatment.

Educational and health outcomes of children and adolescents receiving antidepressant medication: Scotland-wide retrospective record linkage cohort study of 766 237 schoolchildren.

BACKGROUND: Childhood depression is relatively common, under-researched and can impact social and cognitive function and self-esteem. METHODS: Record linkage of routinely collected Scotland-wide administrative databases covering prescriptions [prescribing information system (PIS)], hospitalizations (Scottish Morbidity Records 01 and 04), maternity records (Scottish Morbidity Records 02), deaths (National Records of Scotland), annual pupil census, school absences/exclusions, special educational needs (Scottish Exchange of Educational Data; ScotXed), examinations (Scottish Qualifications Authority) and (un)employment (ScotXed) provided data on 766 237 children attending Scottish schools between 2009 and 2013 inclusively. We compared educational and health outcomes of children receiving antidepressant medication with their peers, adjusting for confounders (socio-demographic, maternity and comorbidity) and explored effect modifiers and mediators. RESULTS: Compared with peers, children receiving antidepressants were more likely to be absent [adjusted incidence rate ratio (IRR) 1.90, 95% confidence interval (CI) 1.85-1.95] or excluded (adjusted IRR 1.48, 95% CI 1.29-1.69) from school, have special educational needs [adjusted odds ratio (OR) 1.77, 95% CI 1.65-1.90], have the lowest level of academic attainment (adjusted OR 3.00, 95% CI 2.51-3.58) and be unemployed after leaving school (adjusted OR 1.88, 95% CI 1.71-2.08). They had increased hospitalization [adjusted hazard ratio (HR) 2.07, 95% CI 1.98-2.18] and mortality (adjusted HR 2.73, 95% CI 1.73-4.29) over 5 years' follow-up. Higher absenteeism partially explained poorer attainment and unemployment. Treatment with antidepressants was less common among boys than girls (0.5% vs 1.0%) but the associations with special educational need and unemployment were stronger in boys. CONCLUSIONS: Children receiving antidepressants fare worse than their peers across a wide range of education and health outcomes. Interventions to reduce absenteeism or mitigate its effects should be investigated.

How well are general practice trainees prepared for paediatric prescribing?

AIMS AND METHODOLOGY: We invited 232 General Practice Trainees to complete an on-line questionnaire to assess how they rated their training for the task of paediatric prescribing and therapeutics in the community. RESULTS: Of the 166 (71%) respondents who completed the questionnaire, 26.5% recalled specific teaching about paediatric prescribing and 59.6% covering one or more relevant topic during their undergraduate years. Undertaking a paediatric post during vocational training was associated with greater prescribing confidence (P < 0.001); however, 35% of respondents were not intending to undertake such a post. CONCLUSION: This study suggests that many GP trainees perceive their paediatric prescribing training as inadequate.

Herbal Medicinal Product Use During Pregnancy and the Postnatal Period: A Systematic Review.

OBJECTIVE: To report the incidence and nature of herbal medicinal products' adverse events and herb-drug interactions used by some pregnant and postnatal women. DATA SOURCES: The Allied and Complementary Medicine Database, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, the Cochrane Library, MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched from inception until August 2018. METHODS OF STUDY SELECTION: Any studies reporting adverse events, herb-drug interactions or absence thereof associated with herbal medicinal products used during pregnancy or the postnatal period were included. Conference abstracts, pilot studies, and nonhuman studies were excluded. All included studies were critically appraised by two independent reviewers. TABULATION, INTEGRATION AND RESULTS: Database searches retrieved 3,487 citations. After duplicate removal and review of titles, abstracts, and full-text, 115 articles were critically appraised. After excluding irrelevant and low-quality articles, 74 articles were included for data extraction and synthesis. Adverse drug reactions, congenital malformations, fetal growth retardation or herb-drug interactions were the primary study objective reported by 19 of the 74 included studies, 16 cohort studies, one cross-sectional survey, and two randomized controlled trials. A total of 47 herbal medicinal products and 1,067,071 women were included in this review. Use of almond oil was associated with preterm birth (odds ratio 2.09, 95% CI 1.07-4.08), oral raspberry leaf was associated with cesarean delivery (adjusted odds ratio [AOR] 3.47, 95% CI 1.45-8.28); heavy licorice use was associated with early preterm birth by 3.07-fold (95% CI 1.17-8.05). African herbal medicine mwanaphepo was associated with maternal morbidity (AOR 1.28; 95% CI 1.09-1.50), and neonatal death or morbidity. Fourteen studies reported absence of adverse events. Four studies reported herb-drug interactions, but none studied adverse events arising from them. CONCLUSION: The use of herbal medicinal products during pregnancy and the postnatal period should be discouraged until robust evidence of safety is available. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42017081058.