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Abstract Objectives--Delays in parenteral antibiotic treatment may contribute to the high mortality in meningococcal disease. This study aimed to record 'door to needle' time in children with meningococcal disease before [...]

Use of unlicensed drugs may be recommended in guidelines EDITOR--Conroy et al report the widespread use of drugs that are either not licensed for use in children or are prescribed [...]

Meningococcal disease can begin suddenly and may kill within hours.[1] Delays in diagnosis and treatment can therefore decrease the chances of survival. The commonest delays in those who die are: [...]

A biphasic activated partial thromboplastin time waveform predicts sepsis and disseminated intravascular coagulation in adults. This has not been previously investigated in children. Our aim is to ascertain whether there are changes in the activated partial thromboplastin time waveform in children with meningococcal disease and to compare its diagnostic use with procalcitonin.

Current knowledge of clinical features of imported childhood malaria is largely limited to small, retrospective, and/or single-center case series. This prospective, population-based study describes the epidemiology and clinical features of imported childhood malaria in children <16 years in the United Kingdom and Republic of Ireland.

OBJECTIVE: To measure the extent of underdosing of antiretroviral drugs in children. Design Multicentre cohort study. Setting Clinical centres in hospitals in the United Kingdom and Ireland in the collaborative HIV paediatric study (CHIPS). Participants 615 HIV infected children aged 2-12 years receiving antiretrovirals. MAIN OUTCOME MEASURES: Doses relative to weight and height compared with current recommended doses in 2004 European guidelines. RESULTS: The CHIPS cohort of 934 children comprises 80% of diagnosed HIV infected children in the UK and Ireland between January 1997 and March 2005, of which 66% (615) aged 2-12 years were prescribed antiretrovirals. Actual doses standardised to weight or surface area varied widely across individual drugs, antiretroviral class, and calendar time, with children underdosed (prescribed less than 90% of current recommended doses) from 6-62% child time at risk. Three serious issues in prescribing antiretrovirals, which may also be relevant to paediatric prescribing in general, were identified. Firstly, dosing was inadequate before incorrect recommendations at licensing were later revised when important pharmacokinetic results emerged. Secondly, guidelines stating dosage alternatives (by weight/surface area) for the same drug led to different and inconsistent doses. And, thirdly, ongoing growth was not adjusted for. CONCLUSIONS: Largely inadvertently, HIV infected children in the United Kingdom and Ireland have been underdosed with antiretrovirals, highlighting problems applicable throughout paediatric prescribing.

This 17-year retrospective review of children with meningococcal disease (MCD) has determined the mortality due to serogroup C, in order to assess the potential impact of a group C conjugate vaccine. Four hundred and forty-nine cases of MCD were admitted to our hospitals during 1977–1993; 78 due to group C, 11 of whom died. There was a significant increase in the proportion of cases due to group C from 1986 onwards (10% vs 21%), and an increase in the total number of cases of MCD (151 vs 298). The currently available group C polysaccharide vaccine has low efficacy below 2 years of age and could not have prevented 54 cases of group C disease. A conjugate group C vaccine administered between 2 and 4 months of age could have prevented 68 cases, including all fatal cases. The recent increase in MCD is partly due to an increase in group C disease. A meningococcal group C conjugate vaccine could prevent most cases of infection due to group C, and decrease the mortality from MCD by up to 30%.

All the solutions of the Dirac equation in the finite space de Sitter universe are found and it is shown that they form a basis for a representation of the group of motions for this universe,SO4,1. The action of the generators ofSO4.1on these solutions is explicitly given as a linear superposition of solutions. Si trovano tutte le soluzioni delle equazioni di Dirac nell'universo di de Sitter dello spazio finito e si mostra che esse formano la baseSO4,1per una rappresentazione del gruppo dei movimenti per questo universo. Su queste soluzioni si dà esplicitamente l'azione dei generatori diSO4,1come sovrapposizione lineare delle soluzioni. Определяются все рещения уравнения Дирака в конечном пространстве вселенной де Ситтера. Показывается, что они образуют базис для представления группы движений для этой вселенной,SO4,1. В явном виде приводится действие генераторовSO4.1на эти решения, в виде линейной суперпозиции решений.

Children with bacterial meningitis often have a full blood count (FBC) measured urgently on admission. We investigated whether urgent FBC gave results that aided immediate management or predicted outcome in children with meningitis. FBCs were measured on admission during 190 episodes of bacterial meningitis in children admitted between 1984 and 1991. Significant anaemia was found in seven children, but immediate transfusion was only necessary in the three subjects who were in the Paediatric Intensive Care Unit (PICU). A white blood count of less than 5 x 10(9) L-1 was significantly associated with death (P < 0.02), but a Glasgow Coma Score of less than 8 predicted death more accurately (positive predictive value of 40%). FBC yielded immediately useful information only in the 15% of children who were admitted to PICU. Conscious level was a better predictor of outcome than FBC. We recommend that urgent FBC should be performed in children with meningitis admitted to a PICU; in other children with meningitis FBC can be analysed during normal laboratory hours. [ABSTRACT FROM PUBLISHER]

This study describes 977 children with imported malaria in England and Wales between 2004 and 2008, focusing on 29 (3.0%) patients admitted to intensive care, of whom 10 had cerebral malaria, 4 required inotropes, and 1 had concurrent septicemia. The remaining 14 were admitted for monitoring only. None died, but 1 child developed cerebellar infarction.

BACKGROUND: Endothelial damage is important in meningococcal disease. Cell adhesion molecules, including P selectin, E selectin, and intercellular cell adhesion molecule 1 (ICAM-1), are expressed by activated endothelium and then subsequently shed. METHODS: ICAM-1, P selectin, and E selectin were measured on admission to hospital in children with meningococcal infections. RESULTS: Concentrations of shed cell adhesion molecules are reported for 78 children. Eleven did not have meningococcal disease. Of the 67 with meningococcal disease, 40 had mild disease (Glasgow meningococcal septicaemia prognostic score (GMSPS) < 8) and 27 had severe disease (GMSPS > or = 8). E selectin and ICAM-1 values were higher in those with meningococcal disease. The E selectin values in those with severe disease were higher than in those with mild disease. P selectin concentrations were not altered in meningococcal disease, but those who died had lower concentrations. CONCLUSIONS: Endothelial activation in meningococcal disease is reflected by shed ICAM-1 and E selectin concentrations.

Meningococcal disease (MCD) can present as meningitis, meningitis plus septicaemia or septicaemia alone. This 17-year retrospective study sought to determine if the proportion of cases presenting as septicaemia alone was increasing. Four hundred and forty-nine children with MCD were admitted between 1977 and 1993, 50 children died (11%). The proportion of cases with septicaemia alone increased from 7% in 1977–1985 to 36% in 1990–1993 (P<0.0005). Mortality was highest in children with septicaemia alone (19%). Despite the increase in septicaemia, overall mortality did not alter over the 17 years.

OBJECTIVE: To measure the promptness of antibiotic treatment in children with meningococcal disease. METHODS: "Door to needle time" for parenteral antibiotics in children with meningococcal disease was recorded prospectively as part of a larger study. The time from arrival at hospital until the first dose of parenteral antibiotics was recorded in 100 children with meningococcal disease (median (range) age 21 (3-168) months) admitted to four Merseyside hospitals. RESULTS: Forty five children presented directly to the accident and emergency (A&E) department. Parenteral penicillin was given before admission to 19 of the 55 children referred by general practitioners (GPs). Median door to needle time was 36 minutes. All children with a typical petechial rash on arrival received antibiotics within 60 minutes. Antibiotics were given sooner to those with severe disease (p = 0.01) and later to those without a rash (p = 0.007). CONCLUSIONS: The first dose of parenteral antibiotics for most children with meningococcal disease was given in A&E. When awareness of meningococcal disease is heightened by ongoing research, those with a petechial rash are treated within 60 minutes. Strategies to improve immediate treatment of meningococcal disease should include education of A&E staff as well as GPs. [ABSTRACT FROM PUBLISHER]

BackgroundLimited data exists, internationally and in Ireland, on long-term outcomes among people with diabetes who are managed in primary care. The Midlands Diabetes Structured Care Programme encompasses evidence-based strategies to structure diabetes management within general practice: patient registration and recall, regular diabetes review visits, active role of the practice nurse in ongoing management, multidisciplinary specialist access, professional education, and remuneration. Our aim was to examine clinical outcome targets, complications and mortality among patients with diabetes enrolled in the programme since its establishment in 1998.MethodsData were collected in 1999, 2003, 2008 and 2015, on outcomes (clinical parameters, complications and mortality) among patients with diabetes (≥18 years) registered with participating practices. Data were extracted from patient notes by clinical nurse specialists using a paper-based data collection form. Cause and date of death were obtained from national death records. Using Stata, chi-square tests were used to test differences in clinical outcomes over time. Cox proportional hazards regression was used to examine the association of baseline factors and mortality.ResultsPatients from 1999 (n=376), were followed up in 2003 (n=229), 2008 (n=96) and 2016 (n=376).The proportion of patients with a recommended blood pressure target (<130/80 mmHg) increased from 9% in 1999 to 26% in 2016 (p<0.001), as did the proportion with a total cholesterol of <4.5 mmol/L (22% vs. 71%, p<0.001), and triglycerides<2.0 mmol/L (47% vs. 81%, p<0.001). The percentage achieving optimal glycaemic control (HbA1c≤7.0%) declined (52% vs. 34%). Between 1999–2016, 22% (n=81) of patients had ever experienced a macrovascular complication; primarily CVA (n=21, 6%), MI (n=16, 4%). In 1999, 18% (n=33) had retinopathy, increasing to 57% (n=59) by 2016. In total, 184 (49%) had died. Between 1999–2013 mortality was higher than background rates in the general population (SMR=2.2, 95% CI 1.9, 2.6). Only 25% (n=46) had cause of death recorded in their GP record. Where cause of death was obtained from national records (n=163), primary causes were MI (n=29, 17.8%) and pneumonia (n=23, 14%). Mean age at death was 77.7±9.3 years. Mortality was significantly higher among patients who were older at baseline. Gender, diabetes type, smoking status and clinical parameters at baseline were not significant predictors of mortality.DiscussionImprovements in the clinical profile of patients enrolled in the programme since its introduction suggests primary-care-led integrated diabetes management can perform favourably in the long-term. However, the high incidence of macrovascular complications, prevalence of retinopathy and mortality rate indicates the importance of effective management.

Breakfast is frequently skipped, particularly among adolescents. Existing research examining the relationship between breakfast skipping and overweight/obesity is predominantly based on cross-sectional data from single country studies; this relationship has not been explored among adolescents across Europe. Our objectives were to examine the demographic factors associated with breakfast skipping, determine the prevalence of skipping among European adolescents, examine differences in macronutrient and food intakes between skippers and non-skippers, and determine whether skipping is associated with overweight/obesity.

BackgroundIn Ireland, more Diabetes Nurse Specialists (DNSs) have been introduced into the community as part of a national programme to standardise and improve diabetes care. DNSs support the delivery of a new model of care whereby uncomplicated type 2 diabetes (T2DM) is managed in primary care, and complicated T2DM is managed between primary and secondary care. Historically diabetes care in Ireland has often been delivered in an unstructured way, lacking integration between primary and secondary care. Given this context we wanted to understand the challenges faced by community-based DNSs in delivering a standardised service.MethodsWe purposively sampled DNSs from community-based respondents to a national survey (n=25) according to four administrative regions of the national health service. We conducted focus groups and interviews using a semi-structured topic guide. Interviews were digitally recorded and transcribed into NVivo V.11 software for coding and analysis. Data analysis is on-going using thematic analysis.ResultsSixteen DNSs participated in 2 focus groups, and 8 interviews. Preliminary analysis suggested elements of the role presented a challenge. As DNSs require their Collaborative Practice Agreement to be signed off by each GP using their service, they were currently unable to prescribe in the community. Despite describing this as ‘frustrating’, DNSs suggested that prescribing could remove opportunities for relationship-building with GPs through discussion of medications. In the community, DNSs lacked the safety net of the hospital team to check things with, and had to work more autonomously, described as ‘daunting’. Role understanding by other staff was another challenge; DNSs felt managers did not understand how the community role should work, which created difficulty when negotiating aspects of the role, including flexible working hours. The lack of a shared record between settings meant patient information from hospital appointments was not readily accessible by DNSs at GP practices and vice versa. This made patient follow-up and case discussion difficult when DNSs were off-site. The absence of administrative support in the role, considered ‘crucial’, was also highlighted. Further interviews with community DNSs are ongoing.ConclusionCommunity-based DNSs faced challenges presented by aspects of their role, their relationship with other staff, their work environment, and the available organisational infrastructure and resources. Although recent policy reforms in Ireland have focused on improving the integrated management of diabetes in the community, findings from this study suggest DNSs may need to be better supported to ensure delivery of a standardised model of diabetes care.

Influenza and pneumococcal vaccines are recommended for certain risk groups. All children admitted to the children’s wards or attending children’s outpatients were studied for these risk factors. Risk factors for influenza were present in 78 (41%) of 193 admissions and 93 (27%) of 348 outpatients. Risk factors for pneumococcal infection were present in 22 (11.5%) admissions and 42 (12%) outpatients. Only 29 of these children had been given influenza (n=19) or pneumococcal (n=10) vaccines. Pediatricians could improve the coverage of influenza and pneumococcal vaccines by identifying children with risk factors in hospital discharge summaries and outpatient clinic letters.