Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups.

BACKGROUND: Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15-20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. METHODS: Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years) and adolescent (14-18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. RESULTS: A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4-20] vs. 7(3-13] vs. 7(3-14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous (p = 0.025), musculoskeletal (p = 0.029), renal (p = 0.027) and cardiorespiratory (p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive (p = 0.034) and exhibited higher anti-dsDNA titres (p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia (p = 0.002), thrombocytopenia (p = 0.004) or low complement (p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. CONCLUSIONS: Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and "classic" autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

Outcomes following mycophenolate mofetil versus cyclophosphamide induction treatment for proliferative juvenile-onset lupus nephritis.

BACKGROUND: Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC). METHODS: UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann-Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis. RESULTS: Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4-8 and 10-14 months post-renal biopsy and last follow-up, in terms of renal British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141-390) days after MMF treatment, and 151 (117-305) days following IVCYC ( p = 0.17). Time to renal flare was 451 (157-1266) days for MMF, and 343 (198-635) days for IVCYC ( p = 0.47). CONCLUSION: This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.

Evaluation of the ACR and SLICC classification criteria in juvenile-onset systemic lupus erythematosus: a longitudinal analysis.

Objectives The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients' classification criteria evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period). Results A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012. Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.

An evidence-based guideline for children presenting with acute breathing difficulty.

OBJECTIVE: The aim of this study was to develop an evidence-based guideline for use primarily by junior clinicians to assist with the management of children presenting to the hospital with an acute breathing difficulty. METHODS: An overview of the literature provided a framework of clinical questions for the management of a child with an acute breathing difficulty on which to base a systematic literature review. Relevant articles were appraised by the research fellow and graded according to their quality. A national panel of 50 clinicians was provided, by post, with the clinical questions, research papers, appraisals and the grades of recommendations generated. They were asked to check the grades allocated to the recommendations and the accuracy of the language used. They were also provided with all the clinical questions for which there was insufficient evidence to reach a conclusion but for which a consensus recommendation was required. A Delphi method was used to formalise the consensus process. For all recommendations, panel members were asked to rate their level of agreement on a 1-9-point Likert scale. The results of the first round were fed back, and appropriate alterations to the recommendations made or additional recommendations included. The process of rating was repeated, and the final guideline was developed based on the consensus reached. RESULTS: Following two iterative rounds, the guideline was completed as a full technical document, with a series of key recommendations and an algorithm. It was based on 10 grade A (evidence from systematic review or meta-analyses), 5 grade B, 17 grade C and 31 grade D (consensus or expert opinion) recommendations. CONCLUSION: We have developed an evidence-based guideline that has subsequently been successfully implemented in the paediatric emergency departments and disseminated nationally. Results showing the effect of the guideline upon practice will be published separately.

Hyponatraemia and hypokalaemia during intravenous fluid administration.

BACKGROUND: Hospital-acquired hyponatraemia is associated with excessive volumes of hypotonic intravenous fluids and can cause death or permanent neurological deficit. METHODS: A cross-sectional survey was carried out in 17 hospitals on all children receiving intravenous fluids during 1 day of a specified week in December 2004. RESULTS: 77 of 99 children receiving intravenous fluids received hypotonic solutions and 38% received >105% of fluid requirements. 21 of 86 children were hyponatraemic, but the electrolytes of only 79% had been checked in the preceding 48 h. CONCLUSIONS: Intravenous fluids should be used with caution as regards the tonicity and volume administered, and with appropriate monitoring of serum electrolytes.

The impact of presenting problem based guidelines for children with medical problems in an accident and emergency department.

AIMS: To evaluate the impact of presenting problem based guidelines in managing children with either diarrhoea (with or without vomiting) or seizure (with or without fever). METHODS: This prospective observational study with an intervention was based on a paediatric accident and emergency (A&E) department in Nottingham. All patients (either GP or self referred) were acute attenders aged 0-15 years, with a medical presenting problem during 4 months in the spring of 1997 and 1999. Five hundred and thirty-one diarrhoea attendances (292 before guideline implementation and 239 after) and 411 seizure attendances (212 before guideline implementation and 199 after) were recorded. Evidence based and consensus ratified guidelines developed for the study were implemented using care pathway documentation. Process (documentation, time in the department, investigations, treatment) and outcome (admission to hospital, returns to A&E) data were collected from case notes. RESULTS: The percentage of children investigated with blood tests fell significantly (haematology requests in diarrhoea presentations from 11% to 4%, biochemistry in seizure presentations from 29% to 17%). Intravenous infusions in diarrhoea presenters fell (9% to 1%), and more appropriate oral fluids were used. Management time in A&E was reduced (diarrhoea presenters: median of 55-40 minutes, seizure presenters: 80-55 minutes, but remained static for other presenting problems). Marked improvements in documentation were seen. Admission rates for diarrhoea attenders increased (27% to 34%) but remained the same for seizure (69% v 73%). CONCLUSIONS: The implementation of a presenting problem based guideline as a care pathway was associated with improvements in the quality of care by: improved documentation; reduced invasive investigations; more appropriate treatment, and reduced time spent in A&E.

An evidence and consensus based guideline for the management of a child after a seizure.

OBJECTIVE: An evidence and consensus based guideline for the management of the child who presents to hospital having had a seizure. It does not deal with the child who is still seizing. The guideline is intended for use by junior doctors, and was developed for this common problem (5% of all paediatric medical attenders) where variation in practice occurs. OPTIONS: Assessment, investigations (biochemistry, lumbar puncture, serum anticonvulsant levels, EEG in particular), and/or admission are examined. OUTCOMES: The guideline aims to direct junior doctors in recognising those children who are at higher risk of serious intracranial pathology including infection, and conversely to recognise those children at low risk who are safe to go home. EVIDENCE: A systematic review of the literature was performed. Articles were identified using the electronic data bases Medline (from 1966 to June 1998), Embase (from 1980 to June 1998) and Cochrane (to June 1998), and selected if they investigated the specified clinical question. Personal reviews were excluded. Selected articles were appraised, graded, and synthesised qualitatively. Statements of recommendation were made. CONSENSUS: An anonymous, postal Delphi consensus development was used. A national panel of 30 medical and nursing staff regularly caring for these children were asked to grade their agreement with the statements generated. They were sent the relevant original publications, the appraisals, and literature review. On the second and third rounds they were asked whether they wished to re-grade their agreement in the light of other panellists' responses. Consensus was defined as 83% of panellists agreeing with the statement. Recommendations in brief: For afebrile seizures all children should have their blood pressure recorded, but no other investigations are routine although a seizing or somnolent child should have blood glucose measured; all children under 1 year should be admitted. For seizures with fever, clinical signs indicating the need to treat as meningitis are given. Children should be admitted if they are under 18 months old, have had a complex seizure, or after pretreatment with antibiotics. VALIDATION: The guideline has undergone implementation and evaluation in a paediatric accident and emergency department, the results of which will be published separately. Only one alteration was made to the guideline as a result of this validation process, which is included here.

An evidence and consensus based guideline for acute diarrhoea management.

OBJECTIVE: To develop an evidence and consensus based guideline for the management of the child who presents to hospital with diarrhoea (with or without vomiting), a common problem representing 16% of all paediatric medical attenders at an accident and emergency department. Clinical assessment, investigations (biochemistry and stool culture in particular), admission, and treatment are addressed. The guideline aims to aid junior doctors in recognising children who need admission for observation and treatment and those who may safely go home. EVIDENCE: A systematic review of the literature was performed. Selected articles were appraised, graded, and synthesised qualitatively. Statements on recommendation were generated. CONSENSUS: An anonymous, postal Delphi consensus process was used. A panel of 39 selected medical and nursing staff were asked to grade their agreement with the generated statements. They were sent the papers, appraisals, and literature review. On the second and third rounds they were asked to re-grade their agreement in the light of other panelists' responses. Consensus was predefined as 83% of panelists agreeing with the statement. RECOMMENDATIONS: Clinical signs useful in assessment of level of dehydration were agreed. Admission to a paediatric facility is advised for children who show signs of dehydration. For those with mild to moderate dehydration, estimated deficit is replaced over four hours with oral rehydration solution (glucose based, 200-250 mOsm/l) given "little and often". A nasogastric tube should be used if fluid is refused and normal feeds started following rehydration. Children at high risk of dehydration should be observed to ensure at least maintenance fluid is tolerated. Management of more severe dehydration is detailed. Antidiarrhoeal medication is not indicated. VALIDATION: The guideline has been successfully implemented and evaluated in a paediatric accident and emergency department.

Determining the common medical presenting problems to an accident and emergency department.

All accident and emergency (A&E) attendances over a one year period were prospectively studied in order to determine common medical presenting problems. Data were collected on children (0-15 years) attending a paediatric A&E department in Nottingham between February 1997 and February 1998. A total of 38 982 children were seen. The diagnoses of 26 756 (69%) were classified as trauma or surgical, and 10 369 (27%) as medical; 1857 (4%) could not be classified. The commonest presenting problems reported for "medical" children were breathing difficulty (31%), febrile illness (20%), diarrhoea with or without vomiting (16%), abdominal pain (6%), seizure (5%), and rash (5%). The most senior doctor seeing these patients in A&E was a senior house officer (intern or junior resident) in 78% of cases, paediatric registrar (senior resident) in 19%, consultant (attending physician) in 1.4%, and "other" in 2.6%. Guidelines developed for A&E should target the commonest presenting problem categories, six of which account for 83% of all medical attendances, and be directed towards senior house officers.

Accounting for overlap? An application of Mezzich's kappa statistic to test interrater reliability of interview data on parental accident and emergency attendance.

STUDY RATIONALE: The number of interview studies with service users is rising because of growth in health services research. The level of agreement between multiple interview data coders requires statistical calculation to support results. Basic kappa statistics are often used but this depends on having mutually exclusive data. Researchers should be aware that this is not valid when an interview word or paragraph can be coded into more than one category. The 'proportional overlap' kappa extension by Mezzich et al. (1981, Journal of Psychiatric Research 16, 29-39) has been investigated as an original solution. OBJECTIVES: To assess the level of agreement beyond chance between several raters of interview data by applying the 'proportional overlap' kappa statistic by Mezzich et al. to verbal interview data. The clinical area investigated was child attendance at an Accident and Emergency Department, where parental attendance experiences have been under-explored. METHODS: Two researchers using a coding schedule coded a random sample of interview transcripts. These data were applied to Mezzich's procedure; coder 1 notes that a paragraph refers to category A and B but coder 2 notes A, B and C. The total agreement overlap in this case was 0.66 because two actual agreements out of three possible agreements were made. This was repeated for each paragraph and divided by the number of coding pairs. All agreement values were summed then subsequently divided by the total number of paragraphs to get Po (total number of observed agreements) and by the total number of coding pairs to get Pe (total number of agreements by chance alone). Po and Pe were used in the basic kappa formula to assess interview coding reliability. RESULTS: The overall mean Po was 0.61, the mean Pe was 0.32, with a kappa score of 0.43; a moderate level of agreement which was statistically significant (t=4.8, P < 0.001, d.f.=23). CONCLUSION: Mezzich's procedure may be applied to interview data to calculate agreement levels between several coders.

Type III tracheal agenesis with familial tetralogy of Fallot and absent pulmonary valve syndrome.

We describe a female infant born at 33 weeks gestation diagnosed postnatally with a previously unreported phenotype consisting of Type III tracheal agenesis plus tetralogy of Fallot with absent pulmonary valve. She was delivered to a mother who had the same congenital heart malformation, but no detectable tracheal abnormality. We discuss possible etiologies of these malformations.

Systemic response to gram-positive and gram-negative infections--comparison and contrast.

The concept of the systemic inflammatory response (SIRS) has recently been defined with suggested new terminology and criteria for diagnosis, and this has gained acceptance in the international literature. The importance of Gram-positive organisms as a cause of the SIRS has become increasingly recognised in recent years. This report describes a case of severe staphylococcal infection with a clinical picture similar to 'classic' endotoxic shock associated with Gram-negative organisms. We use this report to discuss the management of severe sepsis with organ dysfunction, outline the clinical complications and specific therapy of staphylococcal infections, discuss the new terminology, and compare and contrast the features of SIRS associated with varying causes.