This study describes the key areas that matter to adolescent survivors of Invasive Meningococcal Disease (IMD). Satisfaction with Life After Meningitis is a brief multidimensional measure of health related quality of life that is reliable and correlates with criterion variables in a theoretically meaningful way. To develop a Health Related Quality of Life (HRQoL) measure for adolescent and young adult survivors of (IMD) we used a cross-sectional study and focus groups. The study was conducted in two phases. In Phase 1 a pool of potential items were generated based on the following: a review of existing measures, focus groups with IMD survivors, and an expert group consultation. Phase 2 involved administration of the questionnaire to a sample of adolescent and young adult IMD survivors. Factor analysis suggested a correlated four factor solution: Wellbeing, Positive about Future, Social Support, and Confidence. These factors were significantly correlated in a theoretically predictable way with scores from the Beck Depression Inventory (correlations ranged from −0.77 to −0.81) and the eight domains of the SF-36 Health Survey (correlations ranged from 0.32 to 0.79). The reliability of all subscales was high ranging from 0.85 to 0.92. The Satisfaction with Life After Meningitis (SLAM) questionnaire is a HRQoL self-report measure that produces reliable scores and is appropriate for use with young survivors of IMD. There is also evidence of concurrent validity with existing measures of physical and psychological well-being.

A vaccine to prevent pneumococcal meningitis (PM) has recently been introduced. However, contemporary data to inform cost-effectiveness analysis and justify its routine use are sparse. We examined the cognitive, educational, psychological and social outcomes of PM in childhood. We completed a population-based case–control study in two regions of the UK. Children and young people currently between 3 and 20 years of age that had been diagnosed with PM ≤14 years of age were identified from active regional surveillance. Controls were siblings or neighbours of similar age. Standardised questionnaires and neuropsychological testing was administered to assess IQ, educational attainments, memory, psychological distress, quality of life and hearing impairment. Data were available on 97 patients and 93 controls. Eighty-four patients had a sibling/neighbour-matched control. Both matched and unmatched analyses were completed, and results of the 84 matched comparisons were highly similar to the unmatched. For the total sample, controls were similar in age, ethnicity and socioeconomic status. Median age at meningitis was 11 months. Median time between meningitis and assessment was 6.0 years. In the matched analysis, partial or profound hearing impairment was reported in 14% of patients and 1% of controls. Patients had significantly lower mean full-scale IQ (p = 0.05), verbal IQ (p = 0.0008), numeracy (p = 0.02), total quality of life (p = 0.04), school functioning (p = 0.005), psychosocial functioning (p = 0.001) and psychological difficulties (p = 0.01). Parents of patients reported greater functional disability (p = 0.008), impairment in all aspects of quality of life (p = 0.001) and psychological difficulties (p < 0.0006). Findings for IQ were not materially different when analyses were repeated only in those without hearing impairment. In multivariate regression analysis that included both case–control status and hearing status, both being a patient (p = 0.001) and having profound hearing impairment (p = 0.001) were independently associated with lower full-scale IQ. Conclusions Pneumococcal meningitis is associated with major sequelae. Our findings strongly support the introduction of pneumococcal conjugate vaccine as part of routine childhood vaccination programmes internationally.

Aim: To estimate the overall long-term health related quality of life implications of an episode of pneumococcal meningitis in childhood. Method: Cases were identified through two regional UK surveillance studies and traced via their general practitioners (GPs) or local hospital paediatrician. Siblings were used as controls where available. Health related quality of life was assessed using the health utilities index (HUI). Mean utility scores were compared between cases and controls and univariate linear regression was used to identify factors that influenced the overall utility scores. Results: HUI data were available for 71 cases and 66 controls. The mean overall utility score for cases 0.774 (95% CI 0.711– 0.837) was significantly lower than for controls 0.866 (95% CI 0.824–0.907) (p-value = 0.0185). Hearing was the most significantly affected health attribute (p-value < 0.006). In cases, males had lower quality of life scores than females (p-value = 0.018), however this was not seen in controls. Conclusion: An episode of pneumococcal meningitis results in a long-term decrement in overall health related quality of life and is significantly related to hearing loss.

OBJECTIVE. We examined the physical, cognitive, educational, social, and psychological outcomes of invasive meningococcal disease in adolescence, as well as demographic and disease factors associated with outcomes. METHODS. A population-based, matched-cohort study was performed. A total of 101 gender- and age-matched case-control pairs (15–19 years of age at the time of disease; 46% male) from 6 regions of England underwent follow-up evaluations 18 to 36 months after invasive meningococcal disease. Educational, social, and vocational function, mental health, social support, self-efficacy, and quality-of-life data were collected by using standardized questionnaires and neuropsychological tests. RESULTS. Fifty-seven percent of case subjects (n = 58) had major physical sequelae. Survivors had greater depressive symptoms, greater fatigue, less social support, greater reduction in quality of life, and lower educational attainment compared with control subjects. Survivors with serogroup C disease had greater physical sequelae than did those with serogroup B disease. Greater cognitive deficits were associated with younger age at diagnosis. Only 53 of 101 case subjects reported any medical follow-up care after invasive meningococcal disease. CONCLUSIONS. Survivors of invasive meningococcal disease in adolescence have a disturbing series of deficits, including poorer physical and mental health, quality of life, and educational achievement. Serogroup C is associated with poorer outcomes. Invasive meningococcal disease attributable to serogroup B disease remains a major cause of morbidity and death among adolescents. Medical care is poor after discharge from the hospital. Routine follow-up care of adolescent survivors may prevent or ameliorate physical and psychosocial morbidity after invasive meningococcal disease.

Aim: To estimate the overall long-term health related quality of life implications of an episode of pneumococcal meningitis in childhood.Method: Cases were identified through two regional UK surveillance studies and traced via their general practitioners (GPs) or local hospital paediatrician. Siblings were used as controls where available. Health related quality of life was assessed using the health utilities index (HUI). Mean utility scores were compared between cases and controls and univariate linear regression was used to identify factors that influenced the overall utility scores.Results: HUI data were available for 71 cases and 66 controls. The mean overall utility score for cases 0.774 (95% CI 0.711- 0.837) was significantly lower than for controls 0.866 (95% CI 0.824-0.907) (p-value = 0.0185). Hearing was the most significantly affected health attribute (p-value < 0.006). In cases, males had lower quality of life scores than females (p-value = 0.018), however this was not seen in controls.Conclusion: An episode of pneumococcal meningitis results in a long-term decrement in overall health related quality of life and is significantly related to hearing loss.

ABSTRACT Stool samples were collected from infants nursed in two neonatal intensive care units (NICUs) in East London, United Kingdom. The aim of the study was to determine the incidence of and risk factors for the carriage of multiresistant Enterobacteriaceae strains (MRE; resistant to three or more classes of antibiotic) and the extent of the persistence of resistant strains following discharge. Sixty-two (50%) of 124 infants had acquired MRE by 2 weeks of postnatal age, and 69 (56%) infants had acquired MRE by discharge. The proportions of infants at 2 weeks carrying strains that were resistant to antibiotics were the following: tetracycline, 79%; amoxicillin, 78%; cephalosporins, 31%; trimethoprim, 20%; piperacillin-tazobactam, 11%; chloramphenicol, 9%; and aminoglycoside, 4%. A gestational age of less than 26 weeks was a risk factor for colonization with MRE at discharge, but not at 2 weeks. Analysis within a NICU showed that exposure of an infant to a specific antibiotic in the NICU was not a risk factor for the carriage of a strain resistant to that antibiotic. Estimates of persistence from discharge to 6 months were the following: for tetracycline, 57% (95% confidence intervals [CI], 0.35 to 0.87); chloramphenicol, 49% (95% CI, 0.20 to 0.83); trimethoprim, 45% (95% CI, 0.22 to 0.74); piperacillin-tazobactam, 42% (95% CI, 0.20 to 0.71); and augmentin, 34% (95% CI, 0.11 to 0.66). Strains resistant to cephalosporins or aminoglycosides showed lower levels of persistence. Nine of 34 infants (26.5%) with Escherichia coli and 4 (7.1%) of 56 infants with Klebsiella spp. at discharge carried strains indistinguishable by randomly amplified polymorphic DNA and antibiotic susceptibility patterns at 6 months. MRE were found at high frequency in the infants during their stay in the NICU and persisted in a proportion of infants.

Mathematical models have proved to be useful tools for addressing questions about the process of infection. This is because the model allows the investigation of the mathematical link between invisible events (transmission of infection between individuals) and more visible ones (incidence of clinical infection, seroprevalence data etc.). A useful model is often one that is simple enough to provide answers that are applicable to as general a context as possible, but also complex enough so that it can address the most relevant questions. Thus, relatively simple models of viral (or hospital acquired-) infection were used to establish the existence of critical thresholds of immunisation (or antibiotic usage) coverage, although more complex models were needed for the investigation of the impact of infection control practices within more specific contexts. Mathematical models have the potential to elucidate key determinants of the epidemiology of infectious disease arising in infants nursed in neonatal intensive care units.

Post-herpetic neuralgia (PHN) following acute herpes zoster remains a significant cause of neuropathic pain especially in the elderly. Early treatment of the zoster rash with antiviral agents, such as aciclovir remains one of the few measures proven to reduce the incidence and duration of PHN albeit only in a subset of patients. It is therefore crucial that the physician who first sees a case of zoster identifies those patients who are most likely to develop long-term pain and treats them accordingly. In particular, prodrugs such as famciclovir and valaciclvoir may be more beneficial in reducing PHN than the shorter acting aciclovir, but can be more expensive. Measures that could be used to predict patients likely to develop PHN would also facilitate the evaluation of early use of antiepileptic, anti-inflammatory and analgesic agents in the prevention of PHN. In a prospective study of 280 herpes zoster (HZ) cases seen by the general practitioner (GP) we evaluated the predictive value of five clinical factors identified in clinical trials as associated with a higher likelihood of PHN. A visual analogue score (VAS) over 5 and/or age over 50 correctly identified all subjects with PHN at 3 and 6 months, respectively. However, the specificity of this prediction was low because as many as 81% and 85% of those aged over 50 recovered within 3 and 6 months, respectively. Better methods are needed to identify patients over 50 at most risk of PHN that enable GPs to better allocate their resources with respect to HZ treatment.

Problems with antibiotic resistant bacteria are increasing in the hospital and particularly in the intensive care unit. Methicillin-resistant Staphylococcus aureus, Acinetobacter baumanii and extended spectrum beta-lactamase producing Gram-negative bacilli constitute a therapeutic and infection control challenge. Early enteral feeding improves survival in patients in the intensive care unit. Prokinetic agents are routinely used in patients with inappropriate gastrointestinal motility. The use of erythromycin at sub-therapeutic doses as a prokinetic agent is a cause of concern for the following reasons: it can increase the emergence and spread of antibiotic resistance and the likelihood of Clostridium difficile disease. The use of an antibiotic as a prokinetic agent does not constitute prudent antimicrobial prescribing and should be avoided. Alternative agents, whenever possible, should be used.

Aims: To evaluate rates of vitreous relapse among retinoblastoma patients treated with primary chemotherapy and assess diode laser as a potential risk factor for relapse.Methods: Retrospective review of all patients treated with primary chemotherapy at a large ocular oncology centre. Eyes that developed vitreous relapse were coded with regard to Reese-Ellsworth Group, laterality, time to relapse, type of relapse (vitreous base or non-vitreous base relapse), treatments used (including adjuvant diode laser), and ocular preservation. Individual tumour foci treated with laser hyperthermia were also coded for laser parameters including power settings, number of treatments, and concomitant administration of systemic chemotherapy (chemothermotherapy).Results: 15 of 106 eyes (14.15%) developed vitreous relapse over a 6 year period. Mean time to relapse was 7.2 months after chemotherapy was completed. Five cases (33%) were of the vitreous base variety. Ocular salvage was attempted in 11 cases using a variety of methods; one patient was lost to follow up. Six of the remaining 10 eyes (60%) were salvaged. Eight of 38 eyes (21%) treated with systemic chemotherapy and laser hyperthermia developed vitreous relapse compared with seven of 68 eyes (10%) treated with primary chemotherapy alone (p < 0.005). Laser settings, number of hyperthermia treatments, and the concomitant use of systemic chemotherapy (chemothermotherapy) were not associated with higher rates of vitreous relapse.Conclusion: Nearly one in seven eyes with retinoblastoma treated with primary chemotherapy may develop vitreous relapse. The administration of diode laser hyperthermia appears to increase this risk. Despite additional therapy a number of these eyes succumb to enucleation.

Background and Objectives. A large number of patients with thalassemia major have been born and treated exclusively in Cyprus. They have been managed according to standard international practice, but few have been transplanted. In 1999, a combination chelation regime with desferrioxamine and deferiprone was introduced. We analyzed survival trends in Cypriots and tried to identify factors associated with prolonged survival.Design and Methods. We had incomplete information on births pre-1974 and complete information from 1974 onwards. Clinical data were incomplete pre-1980 and complete thereafter. We analyzed data on 539 patients born after 1960 and followed over the period 1980 to the end of 2004.Results. There were 58 deaths, 31 (53.4%) of which where due to cardiac causes. In the complete birth cohort of 284 patients born after 1974, survival (95% CI) at 10, 20 and 30 years was 100% (0); 98.5% (96.1-99.4) and 92.7% (86.7-96.1) respectively. There was a significant trend of increasing cardiac deaths between 1980 and 2000 (p<0.001) and a decline after 2000 (p=0.06). In multivariate survival analysis, protective effects were found for female sex (hazard ratio, 0.37, 95% CI 0.21-0.66; p<0.001), and post-2000 follow-up (hazard ratio, 0.44, 95% CI 0.20-0.99; p<0.05), but not for genotype, treatment center or birth cohort.Interpretation and Conclusions. Most patients born after 1974 survive to at least the age of 30. There has been a marked improvement in survival for patients of all ages since 2000, which may be due to the introduction of combination chelation therapy.

Objective To determine whether suboptimal management in hospital could contribute to poor outcome in children admitted with meningococcal disease.Design Case-control study of childhood deaths from meningococcal disease, comparing hospital care in fatal mid non-fatal cases.Setting National statistics and hospital records.Subjects All children under 17 years who died from meningococcal disease (cases) matched by age with three survivors (controls) from the same region of the country.Main outcome measures Predefined criteria defined optimal management. A panel of paediatricians blinded to the outcome assessed case records using a standardised form and scored patients for suboptimal management.Results We identified 143 cases and 355 controls. Departures from optimal (per protocol) management occurred more frequently in the fatal cases than in the survivors. Multivariate analysis identified three factors independently associated with an increased risk of death: failure to be looked after by a paediatrician, failure of sufficient supervision of junior staff, and failure of staff to administer adequate inotropes. Failure to recognise complications of the disease was a significant risk factor for death, although not independently of absence of paediatric care (P=0.002). The odds ratio for death was 8.7 (95% confidence interval 2.3 to 33) with two failures, increasing with multiple failures.Conclusions Suboptimal healthcare delivery significantly reduces the likelihood of survival in children with meningococcal disease. Improved training of medical and nursing staff, adherence to published protocols, and increased supervision by consultants may improve the outcome for these children and also those with other life threatening illnesses.

Problems with antibiotic resistant bacteria are increasing in the hospital and particularly in the intensive care unit. Methicillin-resistant Staphylococcus aureus , Acinetobacter baumanii and extended spectrum beta-lactamase producing Gram-negative bacilli constitute a therapeutic and infection control challenge. Early enteral feeding improves survival in patients in the intensive care unit. Prokinetic agents are routinely used in patients with inappropriate gastrointestinal motility. The use of erythromycin at sub-therapeutic doses as a prokinetic agent is a cause of concern for the following reasons: it can increase the emergence and spread of antibiotic resistance and the likelihood of Clostridium difficile disease. The use of an antibiotic as a prokinetic agent does not constitute prudent antimicrobial prescribing and should be avoided. Alternative agents, whenever possible, should be used.

Background: For two successive years, 2000 and 2001, there was a world-wide outbreak of W135 meningococcal disease amongst pilgrims who attended the Hajj and in their contacts after returning home.

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain of 6p represented the most frequent event (69% of the tumors), whereas +1q was observed in 57%, confirming that these abnormalities are key secondary events in retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated with tumors displaying adverse histo-prognostic factors, whereas -16q was significantly associated with tumors without adverse features. In three patients who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q, suggesting that these abnormalities may be associated with metastasis. Children >or= 36 months of age at enucleation tended to have more CGH abnormalities per tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q, +13q, -16, and -16q were more frequent in children with an older age at enucleation. Identical CGH changes were found in both tumors from one patient with bilateral tumors, suggesting a common origin. It is possible that tumors displaying loss of 13q and 5q indicate those patients who may suffer an adverse outcome and who would require alternative or more intensive therapy. CGH analysis on larger cohorts and in prospective clinical trials will be invaluable in determining whether a genetic classification of retinoblastoma represents a reliable measure of prognosis.

Objectives: To determine the incidence and to identify the clinical parameters associated with non-gastrointestinal renal tubular and high anion gap acidosis in a cohort of HIV-1-infected children. Methods: Records of 202 HIV-1-infected children were reviewed to identify patients with metabolic acidosis. Serum and urine chemistries of those children with persistent non-gastrointestinal acidosis were then studied prospectively. Serum and urinary anion gaps (SAG and UAG) were calculated. Those with acidosis (group 1) were compared with children without acidosis (group 2). Associations were determined with Pediatric HIV classification, height, weight, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis. Results: Persistent acidosis was noted in 34 out of 202 children (17%): 16 out of 34 (47%, group 1A) had elevated SAG acidosis, and 18 out of 34 (53%) had normal SAG acidosis with a positive UAG (distal renal tubular) acidosis (group 1B). Those with acidifying defects more often received P. carinii pneumonia prophylaxis (P = 0.02 and 0.01 for groups 1 and 1A, respectively) independently of HIV-1 classification. This group was shorter in height than group 2 (P = 0.007). Differences in weight were not significant (P = 0.1). However, acidotic subjects were more immunocompromised than those in group 2 (multivariate P < 0.001 for HIV classification C3). Conclusions: Elevated SAG acidosis and renal tubular acidosis are not uncommon among HIV-infected children with advanced disease. These disorders may be associated with height growth failure and prophylaxis with sulfur/sulfone containing antibiotics. HIV infection and/or its associated therapies may cause renal tubular damage. The causes of elevated SAG acidosis require further investigation.

Aims: To evaluate how tumour size, retinal location, and patient age affect the outcome of retinoblast oma foci treated with chemotherapy.Methods: Retrospective review of retinoblastoma foci treated with primary chemotherapy alone. Individual tumours were coded with regard to their largest basal diameter, location within the eye (macula, macula to equator, equator to ora serrata), and patient's age at diagnosis, Successfully treated tumours required no further intervention while those requiring additional treatment were coded as failures.Results: 56 (72%) tumours responded successfully to chemotherapy alone while 22 (28%) required additional therapy. 26 of 3 1 macular tumours (84%) and 30 of 47 extramacular tumours (64%) responded to chemotherapy (p <0.060). Relative to size, 46 of 60 tumours (77%) greater than 2 mm in basal diameter were successfully treated with chemotherapy, while only 10 of 18 tumours (56%) less than or equal to 2 mm responded (p <0.088). Among the eight tumour foci diagnosed in children less than 2 months of age, five (63%) failed to respond to chemotherapy alone (p <0.032).Conclusion: Retinoblastoma is more likely to respond to primary chemotherapy if it is located in the macula and if the patient is older than 2 months of age. Tumours measuring less than 2 mm in diameter may be less responsive to this treatment.

BACKGROUND:Invasive meningococcal disease, due to Neisseria meningitidis, is an important cause of morbidity and mortality in young children and adolescents. Nasopharyngeal carriage of meningococci (MC), is most prevalent in young adults whereas carriage of Neisseria lactamica (LC), a related non-pathogenic organism, is most prevalent in young children. The objective of this study was to use modelling techniques to test hypotheses on the processes that govern the incidence of meningococcal disease (MD).METHODS:Deterministic compartmental models were fitted to age structured data sets of MC, LC and MD.RESULTS:The model most consistent with the available data sets is one where LC inhibits MC, an inhibition that lasts for a mean of 4.7 years. The hypothesis that LC also acts as a natural immunogen against MD was consistent with this model. The second peak of MD observed among adolescents could be due to the peak in the acquisition of MC in this age group.CONCLUSIONS:The role of LC as a natural immunogen against asymptomatic and symptomatic meningococcal infection was consistent with available field data. If the introduction of novel meningococcal vaccines into a population changes the prevalence of MC or LC, this could have a substantial impact on the effectiveness of immunization programmes. This paper demonstrates the potential utility of modelling to estimate these effects.