Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults

Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.

The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.

[Facial femalization in transgenders].

Transsexualism is a gender identity disorder in which there is a strong desire to live and be accepted as a member of the opposite sex. In male-to-female transsexuals with strong masculine facial features, facial feminization surgery is performed as part of the gender reassignment. A strong association between femininity and attractiveness has been attributed to the upper third of the face and the interplay of the glabellar prominence of the forehead. Studies have shown that a certain lower jaw shape is characteristic of males with special attention to the strong square mandibular angle and chin and also suggest that the attractive female jaw is smaller with a more round shape mandibular angles and a pointy chin. Other studies have shown that feminization of the forehead through cranioplasty have the most significant impact in determining the gender of a patient. Facial feminization surgeries are procedures aimed to change the features of the male face to that of a female face. These include contouring of the forehead, brow lift, mandible angle reduction, genioplasty, rhinoplasty and a variety of soft tissue adjustments. In our maxillofacial surgery department at the Sheba Medical Center we perform forehead reshaping combining with brow lift and at the same surgery, mandibular and chin reshaping to match the remodeled upper third of the face. The forehead reshaping is done by cranioplasty with additional reduction of the glabella area by burring of the frontal bone. After reducing the frontal bossing around the superior orbital rims we manage the soft tissue to achieve the brow lift. The mandibular reshaping, is performed by intraoral approach and include contouring of the angles by osteotomy for a more round shape (rather than the manly square shape angles), as well as reshaping of the bone in the chin area in order to make it more pointy, by removing the lateral parts of the chin and in some cases performing also genioplasty reduction by AP osteotomy.

Emergency management of children with severe sepsis in the United Kingdom: the results of the Paediatric Intensive Care Society sepsis audit.

OBJECTIVE: To audit current UK practice of the management of severe sepsis in children against the 2002 American College of Critical Care Medicine/Pediatric Advanced Life Support (ACCM-PALS) guideline. DESIGN: Prospective observational study. SETTING: 17 UK paediatric intensive care units (PICUs) and two UK PICU transport services. PARTICIPANTS: 200 children accepted for PICU admission within 12 h of arrival in hospital, whether or not successfully transported to a PICU, with a discharge diagnosis of sepsis or suspected sepsis. MAIN OUTCOME MEASURES: Medical interventions, physiological and laboratory data to determine the presence or absence of shock, inter-hospital transfer times, predicted mortality (using the Paediatric Index of Mortality, version 2 (PIM2) scoring system) and observed mortality. RESULTS: 34/200 (17%) children died following referral. Although children defined as being in shock received significantly more fluid (p<0.001) than those who were not in shock, overall fluid and inotrope management suggested by the 2002 ACCM-PALS guideline was not followed in 62% of shocked children. Binary logistic regression analysis demonstrated that the odds ratio for death, if shock was present at PICU admission, was 3.8 (95% CI 1.4 to 10.2, p = 0.008). CONCLUSIONS: The presence of shock at PICU admission is associated with an increased risk of death. Despite clear consensus guidelines for the emergency management of children with severe sepsis and septic shock, most children received inadequate fluid resuscitation and inotropic support in the crucial few hours following presentation.

A child's admission to hospital: a qualitative study examining the experiences of parents.

AIMS: To compare the experiences of parents and children during inpatient admission to either a paediatric intensive care unit (PICU) or a general paediatric ward (GPW) with a specific focus on identifying factors which may influence psychological outcome. METHODS: Semi-structured qualitative interviews of 20 parents whose children had been admitted to hospital. Cases were sampled purposively to ensure representation of both groups (PICU and GPW admissions). Interviews were tape recorded, transcribed and subjected to a thematic analysis. RESULTS: The experiences of parents were explored with regard to illness onset, admission to PICU or GPW and the discharge period. In the PICU group, the sources of stress differed according to the stage: at onset, they were mainly related to their child's illness; during admission, concerns were focused on their child's appearance; finally, on discharge, possible relapse of the illness, impact of the admission on the child and family and the lack of clear follow-up were the central themes. In the GPW group, parents reported similar themes but with lower levels of associated stress. Both groups identified good communication with the medical team and opportunities for participation as helpful in reducing stress. CONCLUSIONS: Admission to hospital is stressful for parents particularly if the child is admitted to PICU. Hospital staff should enhance communication with parents and maximise opportunities for parental participation in the child's treatment. Such interventions may reduce parents' experience of stress during the admission and have the potential to improve psychological outcome.

Treatment of meningococcal infection.

Aggressive early treatment of meningococcal disease can reduce mortality. This relies on prompt recognition and treatment of the complications of septicaemia and meningitis, appropriate ongoing intensive care where necessary, and adequate management of multiple organ failure. Most children with meningococcal disease survive intact, but long term sequelae are increasingly recognised and make follow up essential. New treatments continue to be evaluated, but none has so far proven to be effective in further reducing morbidity or mortality. Simple, timely therapeutic manoeuvres may greatly improve the prospects for survival.

Noninvasive measurement of cardiac output in critically ill children.

This study was performed to evaluate the hemodynamic status of children admitted to the intensive care unit, using suprasternal and transesophageal Doppler ultrasound, and to establish a suitable noninvasive technique to monitor trends in cardiac output in critically ill children. Twenty children were studied over a period of 6 months. The median age was 32.5 months and weight 14.5 kg. Minute distance (MD), which is a linear cardiac output parameter, was assessed. Seven simultaneous pairs of measurements of MD were made using transesophageal Doppler (TED) and suprasternal Doppler (SSD) by the same operator. Following a fluid challenge, seven repeat pairs of measurements were made. The mean percentage changes for MD by TED and SSD were 21.84 (SD 9.97) and 5.75 (SD 7.32). The average coefficients of variation for measurements of MD by TED and SSD were 2.34% and 15.98%, respectively. The mean difference in percentage change between MD, measured by TED and SSD, was 27.59 with a 95% confidence interval and wide limits of agreement. The repeatability of TED measurements was good, but the measurements by SSD were wide and erratic with poor reproducibility. Our study shows that TED is easy to use, reliable, and very useful for monitoring hemodynamic changes in critically ill children.

Choice of fluid for resuscitation of septic shock.

OBJECTIVES: To determine current practice in choice of fluid resuscitation in children following publication of a systematic review that demonstrated a higher mortality in patients treated with human albumin solution. METHODS: A descriptive telephone and postal questionnaire survey directed at the on call paediatric registrar, lead clinician for paediatrics and the paediatric pharmacist at each of 33 hospitals within the Greater London area. The study was coordinated by the Paediatric Intensive Care Unit at St Mary's Hospital, London. The questionnaire was designed to assess whether a protocol/guidelines existed for resuscitation fluid in children with septic shock; whether the participants were aware of the systematic review and if so, had it changed clinical practice. The word "protocol" was used in its broadest sense to include guideline and policy. RESULTS: 11 hospitals had guidelines for fluid resuscitation of septic shock in children. These varied greatly: only three gave clear instructions of which fluid to use and how to use it. Choice of fluid varied widely and there was wide discrepancy between consultant's and registrar's choice of fluid. The systematic review had lead to a change in policy in two thirds of respondents. CONCLUSION: It is apparent that few paediatric departments have a written protocol or guidelines for the management of septic shock that is accessible to all those concerned in the acute treatment of seriously ill children. The systematic review into choice of fluid has had an impact on clinical practice with no data regarding whether this is in the patient's best interests.

Bacterial meningitis: current controversies in approaches to treatment.

Acute bacterial meningitis continues to be a disease with unacceptably high mortality and morbidity rates in both adults and children worldwide, despite advances in antibacterial therapy. Death or permanent disability occurs frequently. The causative organism varies with age, immune function and immunisation status. Infection with Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) is associated with the majority of cases, with Listeria monocytogenes and Streptococcus agalactiae being more prevalent pathogens at the extremes of age (<3 months or >50 years). Antibacterial resistance is an increasing problem, particularly in pneumococcal bacteria but increasingly in other organisms. The increasing prevalence of resistance of pneumococcus to penicillin and the cephalosporins complicates therapy and may have an important impact on treatment outcome. Increased understanding of the pathophysiology has allowed advances in diagnosis and therapy. The use of adjunctive corticosteroids remains controversial, but is probably beneficial in reducing neurological sequelae in children. In adults the evidence is less clear. Vaccination has virtually eradicated Hib meningitis in some countries. Recent introduction of a conjugate vaccine against serogroup C meningococci in the UK has caused a dramatic reduction in the incidence of invasive disease due to this organism. A 7-valent pneumococcal vaccine promises a similar reduction in the incidence of invasive pneumococcal disease. In the meantime, the emergence of widespread resistance of organisms to antibacterial agents, in particular among the common organisms causing bacterial meningitis, remains the biggest challenge in therapy.

Reduction in case fatality rate from meningococcal disease associated with improved healthcare delivery.

BACKGROUND AND AIMS: The case fatality rate from meningococcal disease (MD) has remained relatively unchanged in the post antibiotic era, with 20-50% of patients who develop shock still dying. In 1992 a new paediatric intensive care unit (PICU) specialising in MD was opened. Educational information was disseminated to local hospitals, and a specialist transport service was established which delivered mobile intensive care. The influence of these changes on mortality of children with MD was investigated. METHODS: A total of 331 consecutive children with meningococcal disease admitted to the PICU between 1992 and 1997 were studied. Severity of the disease on admission was assessed using the paediatric risk of mortality (PRISM) score. Logistic regression analysis was used to correct for clinical severity, age, and sex; death was the outcome, and year of admission, a temporal trend variable, was the primary exposure. RESULTS: The case fatality rate fell year on year (from 23% in 1992/93 to 2% in 1997) despite disease severity remaining largely unchanged. After adjustment for age, sex, and disease severity, the overall estimate for improvement in the odds of death was 59% per year (odds ratio for the yearly trend 0.41). CONCLUSIONS: A significant improvement in outcome for children admitted with MD to a PICU has occurred in association with improvements in initial management of patients with MD at referring hospitals, use of a mobile intensive care service, and centralisation of care in a specialist unit.

Evaluation of new treatments for meningococcal disease.

It is recognized that improvement in the practice of clinical medicine, including confirmation of the safety and efficacy of some current interventions, depends greatly on the pursuit of appropriate research. It therefore follows that improved clinical care of children depends on their participation in pediatric research. Furthermore, in the absence of relevant research, harm to children may result. Thus formal studies of therapeutic modalities in children is seen as a moral imperative to ensure that children have equal and safe access to existing and new agents (1).

Increased excretion of urinary glycosaminoglycans in meningococcal septicemia and their relationship to proteinuria.

OBJECTIVES: Meningococcal septic shock is a devastating illness associated with an increase in vascular permeability leading to hypovolemia and accumulation of plasma proteins and fluid in tissues. The capillary leak syndrome is often associated with widespread thrombosis in the skin, limbs, and digits. We postulated that the increase in vascular permeability and the intravascular thrombosis might be caused by an inflammation-induced loss of endothelial and basement membrane glycosaminoglycans (GAGs), which play a role in the permeability and thromboresistant properties of the microvasculature. DESIGN: Prospective, single-center observational study. SETTING: University-affiliated meningococcal research unit and pediatric intensive care unit. PATIENTS: Eighteen children requiring intensive care for meningococcal sepsis, 18 children with steroid-responsive nephrotic syndrome, and 18 healthy control children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum concentrations and urine excretion of glycosaminoglycans were measured and related to changes in glomerular permeability to plasma proteins. The size-distribution and nature of glycosaminoglycans were defined by Polyacrylamide Gel Electrophoresis and specific enzyme digestion. Urinary excretion of heparan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate were significantly increased in meningococcal disease (MD) relative to healthy controls and children with steroid-responsive nephrotic syndrome. The urinary GAGs in MD were of similar size to those in controls when analyzed after pronase digestion. However, analysis of proteoglycan size before proteolytic digestion showed the urinary GAGs in MD were of lower molecular weight and unattached to proteins. The fractional excretion of albumin and immunoglobulin G in MD increased with severity of disease. Patients with severe or fatal MD had albumin clearances overlapping those seen in steroid-responsive nephrotic syndrome. There was a significant correlation between proteinuria in MD and urinary excretion of heparan sulfate (r2 = 0.611, p < .0001), chondroitin-4-sulfate (r2 = 0.721, p < .0001), and chondroitin-6-sulfate (r2 = 0.395, p < .0001). CONCLUSIONS: The capillary leak in meningococcal disease is associated with increased plasma and urine concentrations of GAGs, which may be proteolytically cleaved from endothelial and basement membrane sites. The correlation between the severity of protein leakage and the urine excretion of GAGs suggests that loss of GAGs may be causally related to the increase in permeability to proteins.