Pietro G. Coen

The role of healthcare delivery in the outcome of meningococcal disease in children: case-control study of fatal and non-fatal cases

Abstract 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 and 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.

Risk and protective factors for meningococcal disease in adolescents: matched cohort study

Abstract Objective To examine biological and social risk factors for meningococcal disease in adolescents. Design Prospective, population based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner. Setting Six contiguous regions of England, which represent some 65% of the countrys population. Participants 15-19 year olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls. Methods Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression. Results 144 case control pairs were recruited (74 male (51%); median age 17.6). 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4 to 5.9), intimate kissing with multiple partners (3.7, 1.7 to 8.1), being a university student (3.4, 1.2 to 10) and preterm birth (3.7, 1.0 to 13.5). Religious observance (0.09, 0.02 to 0.6) and meningococcal vaccination (0.12, 0.04 to 0.4) were associated with protection. Conclusions Activities and events increasing risk for meningococcal disease in adolescence are different from in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority.

Retinoblastoma treated with primary chemotherapy alone: The significance of tumour size, location, and age

Aims: To evaluate how tumour size, retinal location, and patient age affect the outcome of retinoblastoma 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 patients 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 31 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.

Comparative Genomic Hybridization of 49 Primary Retinoblastoma Tumors Identifies Chromosomal Regions Associated With Histopathology, Progression, and Patient Outcome

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 ≥ 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.

Outcomes of meningococcal disease in adolescence: prospective, matched-cohort study.

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.

Removing bacteria from hospital surfaces: a laboratory comparison of ultramicrofibre and standard cloths.

We compared the ability of ultramicrofibre-woven cloths with conventional cloths moistened with water only, for their ability to remove several types of organisms relevant to hospital-acquired infections from a variety of surfaces in hospitals. We showed that ultramicrofibre cloths consistently outperformed conventional cloths in their decontamination ability, across all surfaces, and irrespective of whether the bacteria were coated on to the surfaces with phosphate-buffered saline (PBS) or PBS containing horse serum to simulate real-life soiling. The ability of the cloths to remove bacteria from surfaces was assessed by contact plating and colony formation, and by swabbing and measurement of ATP bioluminescence. The results suggest potential for use of ultramicrofibre in healthcare environments. Further studies are required, however, to define accurately how these cloths, which are designed to be used without detergent or biocides, might be capable of safe and effective deployment and recycling in the healthcare environment.

Effectiveness of meningococcal C conjugate vaccine in teenagers in England

Meningococcal C conjugate vaccine was introduced into clinical practice in the UK before phase 3 trials had been undertaken. We therefore did a case-control study in teenagers to assess vaccine effectiveness. All cases (n=31) enrolled had laboratory confirmed meningococcal C disease. We also enrolled between one and three controls (n=65) per case, matched by age, sex, and general practitioner. Three patients and 23 controls had been vaccinated. The protective effectiveness of the vaccine, estimated by conditional logistic regression, was 93% (95% CI 39-99), which is similar to screening method estimates. The estimated protective effectiveness varied little when potential confounding risk factors were taken into account. Our findings indicate that the vaccine is highly protective against invasive meningococcal C disease.

Predicting and preventing post-herpetic neuralgia: Are current risk factors useful in clinical practice?

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.

Influenza and respiratory syncytial virus infections in British Hajj pilgrims

Viral respiratory infections including influenza and respiratory syncytial virus (RSV) have been reported during the Hajj among international pilgrims. To help establish the burden of these infections at the Hajj, we set up a study to confirm these diagnoses in symptomatic British pilgrims who attended the 2005 Hajj. UK pilgrims with symptoms of upper respiratory tract infection (URTI) were invited to participate; after taking medical history, nasal swabs were collected for point-of-care testing (PoCT) of influenza and for subsequent PCR analysis for influenza and RSV. Of the 205 patients recruited, 37 (18%) were positive for either influenza or RSV. Influenza A (H3) accounted for 54% (20/37) of the virus-positive samples, followed by RSV 24% (9/37), influenza B 19% (7/37), and influenza A (H1) 3% (1/37). Of the influenza-positive cases, 29% (8/28) had recently had a flu immunisation. Influenza was more common in those who gave a history of contact with a pilgrim with a respiratory illness than those who did not (17 versus 9%). The overall rate of RSV was 4% (9/202). This study confirms that influenza and RSV cause acute respiratory infections in British Hajj pilgrims. Continuing surveillance and a programme of interventions to contain the spread of infection are needed at the Hajj, particularly when the world is preparing for an influenza pandemic.

Colonization and persistence of antibiotic-resistant Enterobacteriaceae strains in infants nursed in two neonatal intensive care units in East London, United Kingdom.

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.